FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Gach, J Venzon, D Monica, V Brandon, K Franchini, G Forthal, D AF Gach, Johannes Venzon, David Monica, Vaccari Brandon, Keele Franchini, Genoveffa Forthal, Donald TI Vaccine-induced Antibody that Captures but Does Not Neutralize SIVmac251 Increases the Rate of Infection after Low-dose, Repeated Rectal Challenge SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Gach, Johannes; Forthal, Donald] Univ Calif Irvine, Irvine, CA USA. [Venzon, David; Monica, Vaccari; Franchini, Genoveffa] NCI, Bethesda, MD 20892 USA. [Brandon, Keele] Leidos Biomed Res Inc, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA OA14.02 BP 75 EP 75 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600129 ER PT J AU Huang, Y Tomaras, G Andersen-Nissen, E Dintwe, O Morris, L Grunenberg, N Issacs, A DiazGranados, C Sinangil, F Laher, F Swann, E DeRosa, S Ferrari, G Montefiori, D Gilbert, P McElrath, J Corey, L Gray, G AF Huang, Ying Tomaras, Georgia Andersen-Nissen, Erica Dintwe, One Morris, Lynn Grunenberg, Nicole Issacs, Abby DiazGranados, Carlos Sinangil, Faruk Laher, Fatima Swann, Edith DeRosa, Stephen Ferrari, Guido Montefiori, David Gilbert, Peter McElrath, Julie Corey, Lawrence Gray, Glenda CA HVTN097 TI The Relationship between Immune Responses to Tetanus Vaccine, Hepatitis B Vaccine and a Pox-protein HIV Vaccine Regimen SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Huang, Ying; Andersen-Nissen, Erica; Grunenberg, Nicole; Issacs, Abby; DeRosa, Stephen; Gilbert, Peter; McElrath, Julie; Corey, Lawrence] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Tomaras, Georgia; Ferrari, Guido; Montefiori, David] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Andersen-Nissen, Erica] Hutchinson Ctr Res Inst South Africa, Cape Town, South Africa. [Dintwe, One] Univ Cape Town, Rondebosch, South Africa. [Morris, Lynn] Univ KwaZulu Natal, Durban, South Africa. [Morris, Lynn; Laher, Fatima; Gray, Glenda] Univ Witwatersrand, ZA-2050 Johannesburg, South Africa. [DiazGranados, Carlos] Sanofi Pasteur, Swiftwater, PA USA. [Sinangil, Faruk] Global Solut Infect Dis, Princeton, NJ USA. [Swann, Edith] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Gray, Glenda] South African Med Res Council, Tygerberg, South Africa. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA OA14.04 BP 76 EP 76 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600131 ER PT J AU Janes, H Cohen, K Sobieszczyk, M Frahm, N Karuna, S Sanchez, B Magaret, C Adams, E Hammer, S Gilbert, P McElrath, J AF Janes, Holly Cohen, Kristen Sobieszczyk, Magda Frahm, Nicole Karuna, Shelly Sanchez, Brittany Magaret, Craig Adams, Elizabeth Hammer, Scott Gilbert, Peter McElrath, Juliana TI Vaccine-induced CD8+T Cell Immunity Strongly Predicts Lower HIV Infection Risk in HVTN 505 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Janes, Holly; Cohen, Kristen; Frahm, Nicole; Karuna, Shelly; Sanchez, Brittany; Magaret, Craig; Gilbert, Peter; McElrath, Juliana] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Sobieszczyk, Magda; Hammer, Scott] Columbia Univ, Med Ctr, New York, NY 10027 USA. [Adams, Elizabeth] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA OA17.03 BP 85 EP 85 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600148 ER PT J AU Parsons, M Lloyd, S Center, R Swiderek, K LaBranche, C Montefiori, D Keele, B Lifson, J Venturi, V Davenport, M Amarasena, T Kent, S AF Parsons, Matthew Lloyd, Sarah Center, Robert Swiderek, Katherine LaBranche, Celia Montefiori, David Keele, Brandon Lifson, Jeffrey Venturi, Vanessa Davenport, Miles Amarasena, Thakshila Kent, Stephen TI Partial Efficacy of a Broadly Neutralizing Antibody against Cell-associated SHIV Infection SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Parsons, Matthew; Lloyd, Sarah; Amarasena, Thakshila; Kent, Stephen] Univ Melbourne, Melbourne, Vic 3010, Australia. [Center, Robert] Burnet Inst, Melbourne, Vic, Australia. [Swiderek, Katherine] Theraclone, Seattle, WA USA. [LaBranche, Celia; Montefiori, David] Duke Univ, Durham, NC 27706 USA. [Keele, Brandon; Lifson, Jeffrey] NCI, Bethesda, MD 20892 USA. [Venturi, Vanessa; Davenport, Miles] UNSW, Sydney, NSW, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA OA19.02 BP 90 EP 90 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600159 ER PT J AU Steinhardt, J Guenaga, J Mckee, K Louder, M O'Dell, S Chiang, CI Lei, L Doria-Rose, N Mascola, J Li, YX AF Steinhardt, James Guenaga, Javier McKee, Krisha Louder, Mark O'Dell, Sijy Chiang, Chi-I Lei, Lin Doria-Rose, Nicole Mascola, John Li, Yuxing TI Rational Design of Bispecific Antibodies Targeting HIV-1 Env to Achieve Enhanced Anti-viral Potency and Breadth SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Steinhardt, James; Chiang, Chi-I; Lei, Lin; Li, Yuxing] Inst Biosci & Biotechnol Res, Rockville, MD USA. [Guenaga, Javier] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, San Diego, CA USA. [McKee, Krisha; Louder, Mark; O'Dell, Sijy; Doria-Rose, Nicole; Mascola, John] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA OA19.01 BP 90 EP 90 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600158 ER PT J AU Hessell, AJ Jaworski, JP Pandey, S Kahl, C Reed, J Sutton, WF Stanton, JJ Pegu, A Chen, XJ Axthelm, MK Lewis, A Graham, BS Mascola, JR Sacha, JB Haigwood, NL AF Hessell, Ann J. Jaworski, J. Pablo Pandey, Shilpi Kahl, Christoph Reed, Jason Sutton, William F. Stanton, Jeffrey J. Pegu, Amarendra Chen, Xuejun Axthelm, Michael K. Lewis, Anne Graham, Barney S. Mascola, John R. Sacha, Jonah B. Haigwood, Nancy L. CA Passive Immunotherapy TI Durable Marked Attenuation and Clearance of SHIV Infection in Infant Macaques with Human Neutralizing mAbs as Post-exposure Treatment Within 48 Hours SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Hessell, Ann J.; Jaworski, J. Pablo; Pandey, Shilpi; Kahl, Christoph; Sutton, William F.; Stanton, Jeffrey J.; Axthelm, Michael K.; Lewis, Anne; Sacha, Jonah B.; Haigwood, Nancy L.] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Portland, OR 97201 USA. [Hessell, Ann J.; Reed, Jason; Axthelm, Michael K.; Sacha, Jonah B.; Haigwood, Nancy L.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Portland, OR 97201 USA. [Pegu, Amarendra; Chen, Xuejun; Graham, Barney S.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA OA19.03 BP 91 EP 91 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600160 ER PT J AU Lynch, R Madden, P Boritz, E Coates, E Dezure, A Koup, R Graham, B Douek, D Ledgerwood, J Mascola, J AF Lynch, Rebecca Madden, Patrick Boritz, Eli Coates, Emily Dezure, Adam Koup, Richard Graham, Barney Douek, Daniel Ledgerwood, Julie Mascola, John CA VRC 601 Study Team TI Virus Fitness after Infusion with Broadly Neutralizing Antibody VRC01 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Lynch, Rebecca] George Washington Univ, Washington, DC 20052 USA. [Lynch, Rebecca; Madden, Patrick; Boritz, Eli; Coates, Emily; Dezure, Adam; Koup, Richard; Graham, Barney; Douek, Daniel; Ledgerwood, Julie; Mascola, John] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA OA19.04 BP 91 EP 91 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600161 ER PT J AU Astronomo, RD Lemos, MP Narpala, S Czartoski, J Westerberg, K Fleming, L Gross, M Hural, J Tieu, HV Baden, L Rodriguez, B Hammer, S Frank, I Ochsenbauer, C Grunenberg, N Ledgerwood, JE McDermott, A Mayer, K McElrath, MJ AF Astronomo, Rena D. Lemos, Maria P. Narpala, Sandeep Czartoski, Julie Westerberg, Katharine Fleming, Lamar Gross, Mary Hural, John Hong Van Tieu Baden, Lindsey Rodriguez, Benigno Hammer, Scott Frank, Ian Ochsenbauer, Christina Grunenberg, Nicole Ledgerwood, Julie E. McDermott, Adrian Mayer, Kenneth McElrath, M. Juliana TI Rectal and Vaginal Biopsies from Men and Women Infused Intravenously with VRC01 Show Protection in Ex Vivo HIV-1 Challenge SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Astronomo, Rena D.; Lemos, Maria P.; Czartoski, Julie; Westerberg, Katharine; Fleming, Lamar; Gross, Mary; Hural, John; Grunenberg, Nicole; McElrath, M. Juliana] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Narpala, Sandeep; Ledgerwood, Julie E.; McDermott, Adrian] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Hong Van Tieu] New York Blood Ctr, New York, NY 10021 USA. [Baden, Lindsey] Brigham & Womens Hosp, Boston, MA 02115 USA. [Rodriguez, Benigno] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Hammer, Scott] Columbia Univ, Med Ctr, New York, NY 10027 USA. [Frank, Ian] Univ Penn, Philadelphia, PA 19104 USA. [Ochsenbauer, Christina] Univ Alabama Birmingham, Birmingham, AL USA. [Mayer, Kenneth] Fenway Hlth, Boston, MA USA. [Mayer, Kenneth] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Mayer, Kenneth] Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA OA19.05 BP 92 EP 92 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600162 ER PT J AU Carballo-Dieguez, A Balan, IC Giguere, R Dolezal, C Leu, CS Brown, W Ho, T Tuswa-Haynes, C Lama, J Piper, J Richardson, B McGowan, I Cranston, RD AF Carballo-Dieguez, Alex Balan, Ivan C. Giguere, Rebecca Dolezal, Curtis Leu, Cheng-Shiun Brown, William, III Ho, Titcha Tuswa-Haynes, Camagu Lama, Javier Piper, Jeanna Richardson, Barbra McGowan, Ian Cranston, Ross D. CA MTN-017 Protocol Team TI High Levels of Adherence to a Rectal Microbicide Gel and to Oral PrEP Achieved in MTN-017 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Carballo-Dieguez, Alex; Balan, Ivan C.; Giguere, Rebecca; Dolezal, Curtis; Leu, Cheng-Shiun; Brown, William, III; Ho, Titcha; Tuswa-Haynes, Camagu] New York State Psychiat Inst & Hosp, HIV Ctr Clin & Behav Studies, New York, NY 10032 USA. [Carballo-Dieguez, Alex; Balan, Ivan C.; Giguere, Rebecca; Dolezal, Curtis; Leu, Cheng-Shiun; Brown, William, III; Ho, Titcha; Tuswa-Haynes, Camagu] Columbia Univ, New York, NY 10027 USA. [Lama, Javier] Asociac Civil Impacta Salud & Educ, Lima, Peru. [Piper, Jeanna] NIAID, Div AIDS, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Richardson, Barbra] Univ Washington, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. [McGowan, Ian; Cranston, Ross D.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA OA20.01 BP 93 EP 93 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600164 ER PT J AU Palanee-Phillips, T Roberts, S Montgomery, E Reddy, K Govender, V Naidoo, L Siva, S Gaffoor, Z Pather, A Kiweewa, FM Hlahla, K Makinini, B Bunge, K Schwartz, K Torjesen, K Brown, E Soto-Torres, L Baeten, J AF Palanee-Phillips, Thesla Roberts, Sarah Montgomery, Elizabeth Reddy, Krishnaveni Govender, Vaneshree Naidoo, Logashvari Siva, Samantha Gaffoor, Zakir Pather, Arendevi Kiweewa, Flavia Matovo Hlahla, Kudzai Makinini, Bonus Bunge, Katie Schwartz, Katie Torjesen, Kristine Brown, Elizabeth Soto-Torres, Lydia Baeten, Jared CA ASPIRE Study Team TI Frequency of Partner-related Social Harms and their Impact on Adherence to the Dapivirine Vaginal Ring during the MTN020/ASPIRE HIV Prevention Trial SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Palanee-Phillips, Thesla; Reddy, Krishnaveni] Wits Reprod Hlth & HIV Inst, Johannesburg, South Africa. [Roberts, Sarah; Baeten, Jared] Univ Washington, Seattle, WA 98195 USA. [Montgomery, Elizabeth] RTI Int, Womens Global Hlth Imperat, Res Triangle Pk, NC USA. [Govender, Vaneshree; Naidoo, Logashvari; Siva, Samantha; Gaffoor, Zakir; Pather, Arendevi] MRC, Tygerberg, South Africa. [Kiweewa, Flavia Matovo] MU JHU Res Collaborat, Kampala, Uganda. [Hlahla, Kudzai] UC UCSF Collaborat Res Programme, Harare, Zimbabwe. [Makinini, Bonus] John Hopkins Univ Res Project, Coll Med, Blantyre, Malawi. [Bunge, Katie] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Schwartz, Katie; Torjesen, Kristine] FHI 360, Durham, NC USA. [Brown, Elizabeth] FHCRC SCHARP, Seattle, WA USA. [Soto-Torres, Lydia] NIAID, Div AIDS, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA OA20.03 BP 94 EP 94 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600166 ER PT J AU Husnik, MJ Brown, ER Marzinke, M Livant, E Palanee-Phillips, T Hendrix, C Kiweewa, FM Nair, G Soto-Torres, LE Schwartz, K Hillier, SL Baeten, JM AF Husnik, Marla J. Brown, Elizabeth R. Marzinke, Mark Livant, Edward Palanee-Phillips, Thesla Hendrix, Craig Kiweewa, Flavia Matovu Nair, Gonasagrie Soto-Torres, Lydia E. Schwartz, Katie Hillier, Sharon L. Baeten, Jared M. TI Novel Implementation of a Real-time Adherence Monitoring Strategy within a Phase III, Blinded, Placebo-Controlled, HIV-1 Prevention Clinical Trial SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Husnik, Marla J.; Brown, Elizabeth R.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Marzinke, Mark; Hendrix, Craig] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Livant, Edward] Magee Womens Res Inst & Fdn, Pittsburgh, PA USA. [Palanee-Phillips, Thesla] Univ Witwatersrand, ZA-2050 Johannesburg, South Africa. [Kiweewa, Flavia Matovu] MUJHU Res Collaborat, Kampala, Uganda. [Nair, Gonasagrie] Ctr AIDS Programme Res South Africa, Durban, South Africa. [Soto-Torres, Lydia E.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Schwartz, Katie] FHI 360, Durham, NC USA. [Hillier, Sharon L.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Baeten, Jared M.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA OA20.05 BP 95 EP 95 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600168 ER PT J AU Kwong, PD Stewart-Jones, GBE Xu, K Zhou, TQ AF Kwong, Peter D. Stewart-Jones, Guillaume B. E. Xu, Kai Zhou, Tongqing TI Targeted Deglycosylation as a Means of Vaccine Focusing SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Kwong, Peter D.; Stewart-Jones, Guillaume B. E.; Xu, Kai; Zhou, Tongqing] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA OA21.02 BP 96 EP 96 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600171 ER PT J AU Chen, XJ Duan, HY Cheng, C Boyington, J Tian, M Cheng, KL Wang, LS Zhang, Y Frederick, A Mascola, J AF Chen, Xuejun Duan, Hongying Cheng, Cheng Boyington, Jeffery Tian, Ming Cheng, Kwei-Ling Wang, Lingshu Zhang, Yi Frederick, Alt Mascola, John TI Glycan-masking Improves the CD4bs-specificity of Antibodies Elicited by eOD-GT8 60mer SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Chen, Xuejun; Duan, Hongying; Cheng, Cheng; Boyington, Jeffery; Wang, Lingshu; Zhang, Yi; Mascola, John] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD USA. [Tian, Ming; Cheng, Kwei-Ling; Frederick, Alt] Harvard Med Sch, Boston, MA USA. [Tian, Ming; Cheng, Kwei-Ling; Frederick, Alt] Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA OA21.06LB BP 98 EP 98 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600175 ER PT J AU Xu, K Zhou, TQ Mascola, JR Kwong, PD AF Xu, Kai Zhou, Tongqing Mascola, John R. Kwong, Peter D. TI Development of a Soluble HIV-1 Env Trimer Immunogen Stabilized in the Pre-fusion Closed State from Strain CH505 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Xu, Kai; Zhou, Tongqing; Mascola, John R.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA OA21.05 BP 98 EP 98 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600174 ER PT J AU Huang, J Kang, B Ishida, E Griesman, T Wheatley, AK Khurana, S Narpala, SR McDermott, AB Poole, A Bailer, RT Koup, RA Alexander, J Smith, J Migueles, SA Golding, H Wohlbold, TJ Chromikova, V Krammer, F Gurwith, M Connors, M AF Huang, Jinghe Kang, Byong Ishida, Elise Griesman, Trevor Wheatley, Adam K. Khurana, Surender Narpala, Sandeep R. McDermott, Adrian B. Poole, April Bailer, Robert T. Koup, Richard A. Alexander, Jeffrey Smith, Jonathan Migueles, Stephen A. Golding, Hana Wohlbold, Teddy John Chromikova, Veronika Krammer, Florian Gurwith, Marc Connors, Mark TI Upper Respiratory Tract (URT) Administration of a Replication Competent Ad4-H5-Vtn Vaccine Induces Durable Neutralizing Antibody Responses in Humans SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Huang, Jinghe; Kang, Byong; Ishida, Elise; Griesman, Trevor; Poole, April; Migueles, Stephen A.; Connors, Mark] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Wheatley, Adam K.; Narpala, Sandeep R.; McDermott, Adrian B.; Bailer, Robert T.; Koup, Richard A.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Khurana, Surender; Golding, Hana] US FDA, Rockville, MD 20857 USA. [Alexander, Jeffrey; Smith, Jonathan; Gurwith, Marc] PaxVax Inc, San Diego, CA USA. [Wohlbold, Teddy John; Chromikova, Veronika; Krammer, Florian] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA OA22.05 BP 101 EP 101 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600180 ER PT J AU Hural, J Metch, B Grunenberg, N Allen, M Coombs, R Dragavon, J Puren, A Singh, B Maenza, J AF Hural, John Metch, Barbara Grunenberg, Nicole Allen, Mary Coombs, Robert Dragavon, Joan Puren, Adrian Singh, Beverly Maenza, Janine TI HIV Vaccine Trials Network (HVTN) 910: Long-term Follow-up of HIV Vaccine-induced Seropositivity (VISP) among HIV Vaccinees SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Hural, John; Metch, Barbara; Grunenberg, Nicole] Fred Hutchinson Canc Res Ctr, HIV Vaccine Trials Network, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA. [Allen, Mary] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. [Coombs, Robert; Dragavon, Joan; Maenza, Janine] Univ Washington, Seattle, WA 98195 USA. [Puren, Adrian; Singh, Beverly] NICD, NHLS, Johannesburg, South Africa. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA OA22.06 BP 101 EP 101 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600181 ER PT J AU Richardson, SI Lambson, BL Scheepers, C Bhiman, JN Garrett, N Abdool-Karim, S Carrington, M Moore, PL Mkhize, NN Morris, L AF Richardson, Simone Irene Lambson, Bronwen L. Scheepers, Cathrine Bhiman, Jinal N. Garrett, Nigel Abdool-Karim, Salim Carrington, Mary Moore, Penny L. Mkhize, Nonhlanhla N. Morris, Lynn TI Enhanced Effector Functionality of a V2 Broadly Neutralizing Antibody with a Novel IgG3 Fc Allotype SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Richardson, Simone Irene; Lambson, Bronwen L.; Scheepers, Cathrine; Bhiman, Jinal N.; Moore, Penny L.; Mkhize, Nonhlanhla N.; Morris, Lynn] Natl Inst Communicable Dis, Ctr HIV & STIs, Johannesburg, South Africa. [Richardson, Simone Irene; Lambson, Bronwen L.; Scheepers, Cathrine; Bhiman, Jinal N.; Moore, Penny L.; Mkhize, Nonhlanhla N.; Morris, Lynn] Univ Witwatersrand, Fac Hlth Sci, Johannesburg, South Africa. [Garrett, Nigel; Abdool-Karim, Salim; Moore, Penny L.] Univ KwaZulu Natal, CAPRISA, Durban, South Africa. [Carrington, Mary] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. [Carrington, Mary] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA PD02.05LB BP 113 EP 113 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600203 ER PT J AU Chakrabarti, BK Boliar, S Shukla, B Ghobeh, A Chen, WZ Patil, S Guenaga, J Dimitrov, D Wyatt, R AF Chakrabarti, Bimal K. Boliar, Saikat Shukla, Brihaspati Ghobeh, Ali Chen Weizao Patil, Shilpa Guenaga, Javier Dimitrov, Dimiter Wyatt, Richard TI Direct Access to the Co-receptor Binding Site in Virus Is Dependent on Mass of the Inhibitory Molecule and the Length of Variable Loops, V1/V2 of Env SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Chakrabarti, Bimal K.; Boliar, Saikat; Shukla, Brihaspati; Patil, Shilpa] THSTI, Faridabad, Haryana, India. [Ghobeh, Ali; Guenaga, Javier; Wyatt, Richard] IAVI, New York, NY USA. [Chen Weizao; Dimitrov, Dimiter] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA PD05.02 BP 120 EP 120 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600214 ER PT J AU DeKosky, BJ Normandin, E Cheng, C Duan, HY Chen, XJ Kong, R Ransier, A Darko, S Tian, M Cheng, HL Menis, S Kwong, PD Douek, DC Schief, WR Alt, FW Mascola, JR AF DeKosky, Brandon J. Normandin, Erica Cheng, Cheng Duan, Hongying Chen, Xuejun Kong, Rui Ransier, Amy Darko, Sam Tian, Ming Cheng, Hwei-Ling Menis, Sergey Kwong, Peter D. Douek, Daniel C. Schief, William R. Alt, Frederick W. Mascola, John R. TI High-throughput Paired Heavy: Light Antibody Sequencing Enables Genetic Analyses of Broadly Neutralizing Antibody Lineage Development SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [DeKosky, Brandon J.; Normandin, Erica; Cheng, Cheng; Duan, Hongying; Chen, Xuejun; Kong, Rui; Ransier, Amy; Darko, Sam; Kwong, Peter D.; Douek, Daniel C.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Tian, Ming; Cheng, Hwei-Ling; Alt, Frederick W.] Boston Children s Hosp, HHMI, Boston, MA USA. [Menis, Sergey; Schief, William R.] Scripps Res Inst, IAVI, La Jolla, CA 92037 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA PD05.03 BP 121 EP 121 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600215 ER PT J AU Shen, CH Soto, C Stewart-Jones, GB Lemmin, T Kwong, PD AF Shen, Chen-Hsiang Soto, Cinque Stewart-Jones, Guillaume B. Lemmin, Thomas Kwong, Peter D. TI N-linked Glycan Taxonomy and the HIV-1 Glycan Shield SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Shen, Chen-Hsiang; Soto, Cinque; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Stewart-Jones, Guillaume B.] Univ Oxford, Oxford, England. [Lemmin, Thomas] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA PD05.04 BP 121 EP 121 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600216 ER PT J AU Asokan, M Pegu, A Gorman, J Doria-Rose, N Ko, SY Schmidt, S Narpala, S Del Prete, G Chen, XJ Choe, M Li, H Todd, JP Hatziiannou, T McDermott, A Koup, R Keele, B Shaw, G Lifson, J Kwong, P Mascola, J AF Asokan, Mangaiarkarasi Pegu, Amarendra Gorman, Jason Doria-Rose, Nicole Ko, Sung-Youl Schmidt, Stephen Narpala, Sandeep Del Prete, Gregory Chen, Xuejun Choe, Misook Li, Hui Todd, John-Paul Hatziiannou, Theodora McDermott, Adrian Koup, Richard Keele, Brandon Shaw, George Lifson, Jeffrey Kwong, Peter Mascola, John TI Construction and Characterization of Chimeric SHIVs Displaying V1V2 Epitopes that Bind Germline Precursors of Broadly Neutralizing Human Antibodies SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Asokan, Mangaiarkarasi; Pegu, Amarendra; Gorman, Jason; Doria-Rose, Nicole; Ko, Sung-Youl; Schmidt, Stephen; Narpala, Sandeep; Chen, Xuejun; Choe, Misook; Todd, John-Paul; McDermott, Adrian; Koup, Richard; Kwong, Peter; Mascola, John] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Del Prete, Gregory; Keele, Brandon; Lifson, Jeffrey] NCI, ACVP, Leidos Biomed Inc, NIH, Bethesda, MD 20892 USA. [Li, Hui; Shaw, George] Perelman Sch Med, Philadelphia, PA USA. [Hatziiannou, Theodora] Aaron Diamond AIDS Res Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA PD06.01LB BP 123 EP 123 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600217 ER PT J AU Yacoob, C Pancera, M Vigdorovich, V Oliver, BG Sather, DN Glenn, J Feng, JL McGuire, AT Stamatatos, L AF Yacoob, Christina Pancera, Marie Vigdorovich, Vladimir Oliver, Brian G. Sather, D. Noah Glenn, Jolene Feng, Junli McGuire, Andrew T. Stamatatos, Leonidas TI Interactions of Germline VRC01-Class Antibodies with HIV-1 Env: The Role of CDRH3 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Yacoob, Christina; Pancera, Marie; Glenn, Jolene; Feng, Junli; McGuire, Andrew T.; Stamatatos, Leonidas] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Vigdorovich, Vladimir; Oliver, Brian G.; Sather, D. Noah] Ctr Infect Dis Res, Bethesda, MD USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA PD06.02LB BP 123 EP 123 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600218 ER PT J AU Duan, HY Tian, M Cheng, C Chen, XJ Cheng, HL Dekosky, BJ Joyce, MG Dao, M Kimble, M Lin, S Du, Z Chen, YW Chen, YM Cantor, E Huang, PY Jain, S Schief, WR Haynes, BF Alt, FW Mascola, JR AF Duan, Hongying Tian, Ming Cheng, Cheng Chen, Xuejun Cheng, Hwei-Ling Dekosky, Brandon J. Joyce, M. Gordon Dao, Mai Kimble, Michael Lin, Sherry Du, Zhou Chen, Yiwei Chen, Yimin Cantor, Elizabeth Huang, Pei-Yi Jain, Suvi Schief, William R. Haynes, Barton F. Alt, Frederick W. Mascola, John R. TI Selective Activation of VRC01-class Germline Antibodies in Knock-in Mice with Diverse Precursor Repertoires SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Duan, Hongying; Cheng, Cheng; Chen, Xuejun; Dekosky, Brandon J.; Joyce, M. Gordon; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Tian, Ming; Cheng, Hwei-Ling; Dao, Mai; Kimble, Michael; Lin, Sherry; Du, Zhou; Chen, Yiwei; Chen, Yimin; Cantor, Elizabeth; Huang, Pei-Yi; Jain, Suvi; Alt, Frederick W.] Harvard Med Sch, Boston Childrens Hosp, Boston, MA USA. [Schief, William R.] Scripps Res Inst, La Jolla, CA 92037 USA. [Haynes, Barton F.] Duke Human Vaccine Inst, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA PD06.03LB BP 124 EP 124 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600219 ER PT J AU Soumana, D Pancera, M Chen, GY Soto, C Kwong, PD AF Soumana, Djade Pancera, Marie Chen, Gwo-Yu Soto, Cinque Kwong, Peter D. TI Structural Characterization of HIV-1 Entry Inhibitors SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Soumana, Djade; Pancera, Marie; Chen, Gwo-Yu; Soto, Cinque; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA PD08.02 BP 128 EP 128 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600227 ER PT J AU Francis, JN Nishimura, Y Smith, A Welch, B Martin, M Kay, M AF Francis, J. Nicholas Nishimura, Yoshiaki Smith, Amanda Welch, Brett Martin, Malcolm Kay, Michael TI Preclinical Characterization of a Potent D-peptide Inhibitor of HIV Entry: Cholesterol-conjugated PIE12-trimer SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Francis, J. Nicholas; Welch, Brett; Kay, Michael] Navigen, Salt Lake City, UT USA. [Francis, J. Nicholas; Smith, Amanda; Welch, Brett; Kay, Michael] Univ Utah, Salt Lake City, UT 84112 USA. [Nishimura, Yoshiaki; Martin, Malcolm] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA PD08.04LB BP 129 EP 129 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600229 ER PT J AU Mason, R Biris, K Doria-Rose, N Welles, H Nguyen, R O'Dell, S Bailer, R Mascola, J Roederer, M AF Mason, Rosemarie Biris, Kristin Doria-Rose, Nicole Welles, Hugh Nguyen, Richard O'Dell, Sijy Bailer, Robert Mascola, John Roederer, Mario TI Next Generation SIV Broadly Neutralizing Antibodies Mediate Complete Neutralization of SIVmac239 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Mason, Rosemarie; Biris, Kristin; Doria-Rose, Nicole; Welles, Hugh; Nguyen, Richard; O'Dell, Sijy; Bailer, Robert; Mascola, John; Roederer, Mario] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA PD08.05LB BP 130 EP 130 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600230 ER PT J AU Lee, A Donofrio, G Dussupt, V Kong, R Georgiev, I Doria-Rose, N Slike, B Grande, R Bryson, M Mascola, J Robb, M Polonis, V Michael, N Krebs, S AF Lee, Anna Donofrio, Gina Dussupt, Vincent Kong, Rui Georgiev, Ivelin Doria-Rose, Nicole Slike, Bonnie Grande, Rebecca Bryson, Mary Mascola, John Robb, Merlin Polonis, Victoria Michael, Nelson Krebs, Shelly TI Isolation of HIV Specific Monoclonal Antibodies Using a Combined Antigen-specific and B Cell Culture Supernatant Method SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Lee, Anna; Donofrio, Gina; Dussupt, Vincent; Slike, Bonnie; Grande, Rebecca; Bryson, Mary; Robb, Merlin; Polonis, Victoria; Michael, Nelson; Krebs, Shelly] Walter Reed Army Inst Res, US Mil HIV Res Program, Washington, DC USA. [Lee, Anna; Donofrio, Gina; Dussupt, Vincent; Slike, Bonnie; Grande, Rebecca; Bryson, Mary; Robb, Merlin; Krebs, Shelly] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD USA. [Kong, Rui; Doria-Rose, Nicole; Mascola, John] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Georgiev, Ivelin] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P01.01 BP 132 EP 132 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600231 ER PT J AU Cale, E Gorman, J Radakovich, N Crooks, E Osawa, K Ozorowski, G Asokan, M Doria-Rose, N Ward, A Kwong, P Mascola, J Binley, J AF Cale, Evan Gorman, Jason Radakovich, Nathan Crooks, Ema Osawa, Keiko Ozorowski, Gabriel Asokan, Mangai Doria-Rose, Nicole Ward, Andrew Kwong, Peter Mascola, John Binley, James TI A Broadly Neutralizing HIV-1 Antibody with a Non-projecting CDRH3 Loop Engages the V1V2 Apex of Native Envelope Glycoprotein Trimers SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Cale, Evan; Gorman, Jason; Radakovich, Nathan; Asokan, Mangai; Doria-Rose, Nicole; Kwong, Peter; Mascola, John] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Crooks, Ema; Osawa, Keiko; Binley, James] San Diego Biomed Res Inst, San Diego, CA USA. [Ozorowski, Gabriel; Ward, Andrew] Scripps Res Inst, La Jolla, CA 92037 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P01.07 BP 135 EP 135 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600237 ER PT J AU Gorman, J Geng, H Joyce, MG Zhou, TQ Kwong, PD AF Gorman, Jason Geng, Hui Joyce, M. Gordon Zhou, Tongqing Kwong, Peter D. TI Combining Env Trimer Engagement with Germline V1V2-and CD4bs-directed Antibodies SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Gorman, Jason; Geng, Hui; Joyce, M. Gordon; Zhou, Tongqing; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P01.09 BP 136 EP 136 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600239 ER PT J AU Duerr, R Soni, S Banin, A Tuen, M Courtney, C Nanfack, A Mayr, L Redd, A Ding, SL Finzi, A Meli, J Ngai, J Kong, XP Gorny, MK Nyambi, P AF Duerr, Ralf Soni, Sonal Banin, Andrew Tuen, Michael Courtney, Colleen Nanfack, Aubin Mayr, Luzia Redd, Andrew Ding, Shilei Finzi, Andres Meli, Josephine Ngai, Johnson Kong, Xiangpeng Gorny, Miroslaw K. Nyambi, Phillipe TI Three Related HIV-1 Cross-superinfected Individuals Exchange Similar Viral Strains, but Evolve Different Immunological Responses SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Duerr, Ralf; Soni, Sonal; Banin, Andrew; Tuen, Michael; Courtney, Colleen; Nanfack, Aubin; Mayr, Luzia; Kong, Xiangpeng; Gorny, Miroslaw K.; Nyambi, Phillipe] NYU, Sch Med, New York, NY 10003 USA. [Redd, Andrew] NIAID, NIH, Bethesda, MD USA. [Ding, Shilei; Finzi, Andres] Univ Montreal, Montreal, PQ, Canada. [Meli, Josephine; Ngai, Johnson] Med Diagnost Ctr, Yaounde, Cameroon. [Nyambi, Phillipe] Manhattan Vet Affairs Harbor Healthcare Syst, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P01.20 BP 141 EP 141 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600249 ER PT J AU Wang, YM Dell, SO Guenaga, J Chiang, CI Lei, L Wilson, R Doria-Rose, N Mascola, J Wyatt, R Hedestam, GK Li, YX AF Wang, Yimeng Dell, Sijy O. Guenaga, Javier Chiang, Chi-I Lei, Lin Wilson, Richard Doria-Rose, Nicole Mascola, John Wyatt, Richard Hedestam, Gunilla Karlsson Li, Yuxing TI HIV-1 Env Immunogen-elicited Cross-reactive Tier 2 Virus Neutralizing Antibody Response in Non-human Primates SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Wang, Yimeng; Wyatt, Richard; Li, Yuxing] Scripps Res Inst, La Jolla, CA 92037 USA. [Wang, Yimeng; Chiang, Chi-I; Lei, Lin; Li, Yuxing] Univ Maryland, College Pk, MD 20742 USA. [Dell, Sijy O.; Doria-Rose, Nicole; Mascola, John] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Guenaga, Javier; Wilson, Richard; Wyatt, Richard; Li, Yuxing] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA USA. [Hedestam, Gunilla Karlsson] Karolinska Inst, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P01.24 BP 143 EP 143 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600253 ER PT J AU Gift, SK Wieczorek, L Krebs, SJ Molnar, S Donofrio, G Chenine, AL Sanders-Buell, E Kijak, G Chang, D Doria-Rose, N Rolland, M Tovanabutra, S Sriplienchan, S Nitayapan, S Connell, RJO Eller, LA Mascola, J Michael, NL Robb, ML Polonis, VR AF Gift, Syna K. Wieczorek, Lindsay Krebs, Shelly J. Molnar, Sebastian Donofrio, Gina Chenine, Agnes-Laurence Sanders-Buell, Eric Kijak, Gustavo Chang, David Doria-Rose, Nicole Rolland, Morgane Tovanabutra, Sodsai Sriplienchan, Somchai Nitayapan, Sorachai Connell, Robert J. O. Eller, Leigh-Anne Mascola, John Michael, Nelson L. Robb, Merlin L. Polonis, Victoria R. TI Development of Autologous Neutralizing Antibodies in HIV-1 CRF01_AE-infected Patients Spanning the First Three Years of Infection SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Gift, Syna K.; Wieczorek, Lindsay; Krebs, Shelly J.; Molnar, Sebastian; Donofrio, Gina; Chenine, Agnes-Laurence; Sanders-Buell, Eric; Kijak, Gustavo; Chang, David; Rolland, Morgane; Tovanabutra, Sodsai; Eller, Leigh-Anne; Michael, Nelson L.; Robb, Merlin L.; Polonis, Victoria R.] US Mil HIV Res Program, Bethesda, MD USA. [Gift, Syna K.; Wieczorek, Lindsay; Krebs, Shelly J.; Molnar, Sebastian; Donofrio, Gina; Chenine, Agnes-Laurence; Sanders-Buell, Eric; Kijak, Gustavo; Chang, David; Tovanabutra, Sodsai; Eller, Leigh-Anne; Robb, Merlin L.] Henry M Jackson Fdn Advancement Mil Med, Bethesda, MD USA. [Doria-Rose, Nicole; Mascola, John] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Sriplienchan, Somchai; Nitayapan, Sorachai; Connell, Robert J. O.] Armed Forces Res Inst Med Sci, Bangkok, Thailand. [Michael, Nelson L.; Polonis, Victoria R.] Walter Reed Army Inst Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P01.30 BP 146 EP 146 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600259 ER PT J AU Lei, L Tran, K Chiang, CI Wang, YM Arendt, HE DeStefano, J Xiao, YL Wyatt, RT Li, YX AF Lei, Lin Tran, Karen Chiang, Chi-I Wang, Yimeng Arendt, Heather E. DeStefano, Joanne Xiao, Yongli Wyatt, Richard T. Li, Yuxing TI Antibody Responses Elicited by Cleaved Soluble HIV-1 Envelope Trimers in Guinea Pigs Revealed by Single B Cell Sorting and Cloning SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Lei, Lin; Chiang, Chi-I; Wang, Yimeng; Li, Yuxing] Univ Maryland, Inst Biosci & Biotechnol Res, College Pk, MD 20742 USA. [Tran, Karen; Wyatt, Richard T.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA. [Arendt, Heather E.; DeStefano, Joanne] Int AIDS Vaccine Initiat, New York, NY USA. [Xiao, Yongli] NIAID, Lab Infect Dis, NIH, Rockville, MD USA. Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P01.34LB BP 148 EP 148 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600263 ER PT J AU Montefiori, D Seaman, M Korber, B Wagh, K Morris, L Zolla-Pazner, S Lu, S Corey, L Scarlatti, G D'Souza, P AF Montefiori, David Seaman, Michael Korber, Bette Wagh, Kshitij Morris, Lynn Zolla-Pazner, Susan Lu, Shan Corey, Larry Scarlatti, Gabriella D'Souza, Patricia TI Tier 1 Strains of HIV-1: Time to Break an Old Habit? SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Montefiori, David] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Seaman, Michael] Harvard, Beth Isreal Deaconess Med Ctr, Cambridge, MA USA. [Korber, Bette; Wagh, Kshitij] Los Alamos Natl Lab, Los Alamos, NM USA. [Korber, Bette; Wagh, Kshitij] New Mexico Consortium, Los Alamos, NM USA. [Morris, Lynn] Natl Inst Communicable Dis, Johannesburg, South Africa. [Zolla-Pazner, Susan] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Lu, Shan] Univ Massachusetts, Sch Med, Amherst, MA 01003 USA. [Corey, Larry] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Scarlatti, Gabriella] Global HIV Vaccine Enterprise, New York, NY USA. [D'Souza, Patricia] NIAID, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P01.33LB BP 148 EP 148 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600262 ER PT J AU Levendosky, K Barnable, P Mizenina, O Zydowsky, TM O'Keefe, BR Derby, N Teleshova, N Fernandez-Romero, JA AF Levendosky, Keith Barnable, Patrick Mizenina, Olga Zydowsky, Thomas M. O'Keefe, Barry R. Derby, Nina Teleshova, Natalia Fernandez-Romero, Jose A. TI Comparative Assessment of the Potency and Breadth of Activity of Griffithsin and Broad Neutralizing Antibodies Against HIV SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Levendosky, Keith; Barnable, Patrick; Mizenina, Olga; Zydowsky, Thomas M.; Derby, Nina; Teleshova, Natalia; Fernandez-Romero, Jose A.] Populat Council, 1230 York Ave, New York, NY 10021 USA. [O'Keefe, Barry R.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21701 USA. Borough Manhattan Community Coll, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P01.35LB BP 149 EP 149 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600264 ER PT J AU Teigler, JE Eller, MA Bolton, D Marovich, M Robb, ML Martin, JN Deeks, SG Michael, NL Streeck, H AF Teigler, Jeffrey E. Eller, Michael A. Bolton, Diane Marovich, Mary Robb, Merlin L. Martin, Jeffrey N. Deeks, Steven G. Michael, Nelson L. Streeck, Hendrik TI Differential Impact of Inhibitory Receptors and Inhibitory Receptor Blockade on Cytokine-producing CD4 T Cell Subsets SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Teigler, Jeffrey E.; Eller, Michael A.; Bolton, Diane; Robb, Merlin L.; Michael, Nelson L.; Streeck, Hendrik] Henry M Jackson Fdn Advancement Mil Med, Bethesda, MD USA. [Teigler, Jeffrey E.; Eller, Michael A.; Bolton, Diane; Robb, Merlin L.; Michael, Nelson L.; Streeck, Hendrik] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA. [Marovich, Mary] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Martin, Jeffrey N.] Dept Epidemiol & Biostat, Bethesda, MD USA. [Deeks, Steven G.] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. [Streeck, Hendrik] Inst HIV Res, Essen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P03.08 BP 169 EP 169 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600303 ER PT J AU Hu, XT Valentin, A Dayton, F Kulkarni, V Alicea, C Rosati, M Chowdhury, B Gautam, R Broderick, KE Sardesai, NY Martin, MA Mullins, JI Pavlakis, GN Felber, BK AF Hu, Xintao Valentin, Antonio Dayton, Frances Kulkarni, Viraj Alicea, Candido Rosati, Margherita Chowdhury, Bhabadeb Gautam, Rajeev Broderick, Kate E. Sardesai, Niranjan Y. Martin, Malcolm A. Mullins, James I. Pavlakis, George N. Felber, Barbara K. TI Novel pDNA Prime-boost Vaccine Regimen to Augment Magnitude, Breadth, and Cytotoxicity of Cellular Immunity to Subdominant Gag Epitope of HIV and SIV SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Hu, Xintao; Valentin, Antonio; Dayton, Frances; Kulkarni, Viraj; Alicea, Candido; Rosati, Margherita; Chowdhury, Bhabadeb; Pavlakis, George N.; Felber, Barbara K.] NCI, Frederick, MD 21701 USA. [Gautam, Rajeev; Martin, Malcolm A.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Broderick, Kate E.; Sardesai, Niranjan Y.] Inovio Pharmaceut, Plymouth Meeting, PA USA. [Mullins, James I.] Univ Washington, Seattle, WA 98195 USA. RI bebarta, vikhyat/K-3476-2015 NR 0 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P03.13 BP 172 EP 172 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600308 ER PT J AU Mhlanga, F Singh, D Kamira, B Bunge, K Harkoo, I Chappell, C Mukaka, S Palanee-Phillips, T Crida, D Nakabiito, C Szydlo, D Kachipapa, E Pather, A Baeten, J Mvelase, S Mdlala, B Piper, J Balkus, J Hillier, S AF Mhlanga, Felix Singh, Devika Kamira, Betty Bunge, Katherine Harkoo, Ishana Chappell, Catherine Mukaka, Shorai Palanee-Phillips, Thesla Crida, Danielle Nakabiito, Clemensia Szydlo, Danny Kachipapa, Emma Pather, Aren Baeten, Jared Mvelase, Samkelisiwe Mdlala, Bernadette Piper, Jeanna Balkus, Jen Hillier, Sharon TI Uptake of Non-hormonal Intrauterine Contraceptive Devices (IUDs) among Women Participating in MTN-020, a Clinical Trial for HIV Prevention in Africa SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Mhlanga, Felix] Univ Zimbabwe, Coll Hlth Sci, Harare, Zimbabwe. [Singh, Devika; Bunge, Katherine; Hillier, Sharon] Microbicides Trials Network, Durham, NC USA. [Kamira, Betty; Nakabiito, Clemensia] Makerere Univ Johns Hopkins Univ, Kampala, Uganda. [Harkoo, Ishana] CAPRISA, Durban, South Africa. [Chappell, Catherine] Magee Womens Res Inst, Pittsburgh, PA USA. [Mukaka, Shorai] Univ Zimbabwe Univ Calif, San Francisco Collaborat Res Program, Harare, Zimbabwe. [Palanee-Phillips, Thesla] Wits Reprod Hlth & HIV Inst, Johannesburg, South Africa. [Crida, Danielle] Desmond Tutu HIV Ctr, Cape Town, South Africa. [Szydlo, Danny; Balkus, Jen] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Kachipapa, Emma] UNC Project, Lilongwe, Malawi. [Pather, Aren; Mvelase, Samkelisiwe; Mdlala, Bernadette] Med Res Council South Africa, Tygerberg, South Africa. [Baeten, Jared] Global Hlth Univ Washington, Seattle, WA USA. [Piper, Jeanna] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P05.06 BP 190 EP 190 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600345 ER PT J AU Lowry, A Walker, CM O'Neill, CI Swartz, GM Turpin, JA Cummins, JE AF Lowry, Anabel Walker, Cattlena M. O'Neill, Cynthia I. Swartz, Glenn M. Turpin, Jim A. Cummins, James E., Jr. TI Best Practices for Use of the Rabbit Rectal Irritation (RRI) Model for Assessing the Safety and Systemic Exposure of Rectal Gel Microbicides SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Lowry, Anabel; Turpin, Jim A.; Cummins, James E., Jr.] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. [Walker, Cattlena M.; O'Neill, Cynthia I.; Swartz, Glenn M.] Adv BioSci Labs Inc, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P06.01 BP 199 EP 199 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600361 ER PT J AU Marshall, LJ O'Neill, CI Desai, R Goykhman, D Madsen, TJ Polsky-Fisher, S Sanchez, RI Strizki, J Turpin, JA van Laarhoven, H Veronese, F Swartz, GM Cummins, JE AF Marshall, Leslie J. O'Neill, Cynthia I. Desai, Rajesh Goykhman, Dina Madsen, Timothy J. Polsky-Fisher, Stacey Sanchez, Rosa I. Strizki, Julie Turpin, Jim A. van Laarhoven, Hans Veronese, Fulvia Swartz, Glenn M. Cummins, James E. TI Utility of the Sheep Model for Testing the 28-day MK-2048A Intravaginal Ring and Determining the Correlates of Exposure for Vicriviroc and MK-2048 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Marshall, Leslie J.; Turpin, Jim A.; Veronese, Fulvia; Cummins, James E.] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. [O'Neill, Cynthia I.; Swartz, Glenn M.] Adv Biosci Labs Inc, Rockville, MD USA. [Desai, Rajesh; Goykhman, Dina; Polsky-Fisher, Stacey; Sanchez, Rosa I.; Strizki, Julie] Merck & Co Inc, Merck Res Labs, Kenilworth, NJ USA. [Madsen, Timothy J.] Sinclair Res Ctr LLC, Auxvasse, MO USA. [van Laarhoven, Hans] Merck & Co Inc, Schiphol Rijk, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P06.07 BP 202 EP 202 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600367 ER PT J AU Spreen, W Lowry, A Pal, R Yueh, YL Ford, S Richardson-Harman, N Turpin, JA Veronese, F Cummins, J AF Spreen, William Lowry, Anabel Pal, Ranajit Yueh, Yun Lan Ford, Susan Richardson-Harman, Nicola Turpin, Jim A. Veronese, Fulvia Cummins, James CA ABL BIOQUAL NHP Team TI Use of a "Lead-in" Pharmacokinetic (PK) Study to Predict the Tissue Concentration of Cabotegravir that Protects Macaques against SIV Infection SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Spreen, William; Yueh, Yun Lan; Ford, Susan] GlaxoSmithKline, Philadelphia, PA USA. [Lowry, Anabel; Turpin, Jim A.; Veronese, Fulvia; Cummins, James] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. [Pal, Ranajit] Adv BioSci Labs Inc, Rockville, MD USA. [Richardson-Harman, Nicola] Alpha StatConsult LLC, Damascus, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P06.13 BP 205 EP 205 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600373 ER PT J AU Patamawenu, AA Connors, M AF Patamawenu, Apisit A. Connors, Mark TI Truncated HIV Envelope Expressed by Synthetic Recombinant Replication-competent (SRRC) Human Ad4 Recognized by Conformation-dependent Antibodies SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Patamawenu, Apisit A.; Connors, Mark] NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P07.04 BP 209 EP 209 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600381 ER PT J AU Calenda, G Barnable, P Levendosky, K Kleinbeck, K Fernandez-Romero, JA Keefe, BO Zydowsky, TM Teleshova, N AF Calenda, Giulia Barnable, Patrick Levendosky, Keith Kleinbeck, Kyle Fernandez-Romero, Jose A. Keefe, Barry O. Zydowsky, Thomas M. Teleshova, Natalia TI GRFT/Carrageenan Gel Inhibits HIV and HSV-2 in Human Cervical Mucosa SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Calenda, Giulia; Barnable, Patrick; Levendosky, Keith; Kleinbeck, Kyle; Fernandez-Romero, Jose A.; Zydowsky, Thomas M.; Teleshova, Natalia] Populat Council, 1230 York Ave, New York, NY 10021 USA. [Keefe, Barry O.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P07.19 BP 217 EP 217 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600396 ER PT J AU Francica, J Lynn, G Laga, R Aussedat, B Meyerhoff, R Alam, M Danishefsky, S Haynes, B Seder, R AF Francica, Joseph Lynn, Geoffrey Laga, Richard Aussedat, Baptiste Meyerhoff, Ryan Alam, Munir Danishefsky, Samuel Haynes, Barton Seder, Robert TI Synthetic Biocompatible Polymers Are an Effective Delivery Platform That Elicits Potent Antibody Responses Against HIV-1 Glycopeptide Immunogens SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Francica, Joseph; Lynn, Geoffrey; Seder, Robert] NIH, Bldg 10, Bethesda, MD 20892 USA. [Laga, Richard] Inst Macromol Chem, Prague, Czech Republic. [Aussedat, Baptiste; Danishefsky, Samuel] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Meyerhoff, Ryan; Alam, Munir; Haynes, Barton] Duke Human Vaccine Inst, Durham, NC USA. RI Laga, Richard/G-3627-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P07.27 BP 221 EP 221 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600404 ER PT J AU Jhunjhunwala, K Sant, V Wang, L Graebing, P Marshall, L Cummins, J Walker, C Swartz, G Rohan, L AF Jhunjhunwala, Kunal Sant, Vinayak Wang, Lin Graebing, Phil Marshall, Leslie Cummins, James, Jr. Walker, Cattlena Swartz, Glenn Rohan, Lisa TI Development of a Suppository Dosage Form for the Integrase Inhibitor, MK-2048 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Jhunjhunwala, Kunal; Sant, Vinayak; Rohan, Lisa] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA 15260 USA. [Jhunjhunwala, Kunal; Wang, Lin; Graebing, Phil; Rohan, Lisa] Univ Pittsburgh, Magee Womens Res Inst, Pittsburgh, PA 15260 USA. [Marshall, Leslie; Cummins, James, Jr.] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. [Walker, Cattlena; Swartz, Glenn] Adv Biosci Labs Inc, Rockville, MD USA. [Rohan, Lisa] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P07.33 BP 224 EP 224 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600410 ER PT J AU Lai, YT Pancera, M Stewart-Jones, G Druz, A Kwong, P AF Lai, Yen-Ting Pancera, Marie Stewart-Jones, Guillaume Druz, Alex Kwong, Peter TI Improving Structural Accuracy of HIV-1 env Trimeric Structure by Crystal Lattice Engineering and the Potential Application in Drug Discovery SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Lai, Yen-Ting; Pancera, Marie; Stewart-Jones, Guillaume; Druz, Alex; Kwong, Peter] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P08.07 BP 235 EP 235 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600431 ER PT J AU Chambers, MJ Narpala, SR Prabhakaran, MS Acharya, P Pancera, M Kwon, YD Cheng, C Zhou, TQ Gorman, J Joyce, GM Georgiev, IS Zhang, BS Mascola, JR Koup, RA Kwong, PD McDermott, AB AF Chambers, Michael J. Narpala, Sandeep R. Prabhakaran, Madhu S. Acharya, Priyamvada Pancera, Marie Kwon, Young D. Cheng, Cheng Zhou, Tongqing Gorman, Jason Joyce, Gordon M. Georgiev, Ivelin S. Zhang, Baoshan Mascola, John R. Koup, Richard A. Kwong, Peter D. McDermott, Adrian B. TI Antigenic Characterization of HIV-1 Trimers Using Meso Scale Discovery ECLIA SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Chambers, Michael J.; Narpala, Sandeep R.; Prabhakaran, Madhu S.; Acharya, Priyamvada; Pancera, Marie; Kwon, Young D.; Cheng, Cheng; Zhou, Tongqing; Gorman, Jason; Joyce, Gordon M.; Georgiev, Ivelin S.; Zhang, Baoshan; Mascola, John R.; Koup, Richard A.; Kwong, Peter D.; McDermott, Adrian B.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD USA. [Pancera, Marie] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. Vanderbilt Univ, Sch Med, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P08.11 BP 237 EP 237 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600435 ER PT J AU Kleinbeck, K Bonnaire, T Kizima, L Rodriguez, A Grecky, S Levendosky, K Katzen, L O'Keefe, BR Makovec, T Peet, M Creasy, G Zydowsky, TM Fernandez-Romero, JA AF Kleinbeck, Kyle Bonnaire, Thierry Kizima, Larisa Rodriguez, Aixa Grecky, Susanna Levendosky, Keith Katzen, Lauren O'Keefe, Barry R. Makovec, Tracy Peet, Melissa Creasy, George Zydowsky, Thomas M. Fernandez-Romero, Jose A. TI Toxicology Profile of a Topical Multipurpose Prevention Technology that Combines Griffithsin and Carrageenan SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Kleinbeck, Kyle; Bonnaire, Thierry; Kizima, Larisa; Rodriguez, Aixa; Grecky, Susanna; Levendosky, Keith; Katzen, Lauren; Creasy, George; Zydowsky, Thomas M.; Fernandez-Romero, Jose A.] Populat Council, New York, NY USA. [O'Keefe, Barry R.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21701 USA. [Makovec, Tracy; Peet, Melissa] MPI Res Inc, Mattawan, MI USA. Borough Manhattan Community Coll, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P08.18LB BP 240 EP 240 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600442 ER PT J AU Levendosky, K Mizenina, O Aravantinou, M Kleinbeck, K Bonnaire, T Derby, N Zydowsky, TM O'Keefe, BR Fernandez-Romero, JA AF Levendosky, Keith Mizenina, Olga Aravantinou, Meropi Kleinbeck, Kyle Bonnaire, Thierry Derby, Nina Zydowsky, Thomas M. O'Keefe, Barry R. Fernandez-Romero, Jose A. TI Preclinical Evaluation of a Griffithsin/Carrageenan Formulation to Prevent HIV Infection SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Levendosky, Keith; Mizenina, Olga; Aravantinou, Meropi; Kleinbeck, Kyle; Bonnaire, Thierry; Derby, Nina; Zydowsky, Thomas M.; Fernandez-Romero, Jose A.] Populat Council, New York, NY USA. [O'Keefe, Barry R.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD USA. Borough Manhattan Community Coll, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P08.17LB BP 240 EP 240 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600441 ER PT J AU Dawson, L AF Dawson, Liza TI Ethical Issues in Design of Prevention Trials: Grappling with Changing Standards of Prevention SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Dawson, Liza] NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P10.01 BP 255 EP 255 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600469 ER PT J AU deCamp, AC Rolland, M Edlefsen, PT Sanders-Buell, E Hall, B Magaret, C Fiore-Gartland, AJ Juraska, M Graham, BS Roederer, M Michael, NL Robb, ML McElrath, J Tovanabutra, S Sobieszczyk, ME Hammer, SM Kim, JH Mullins, JI Gilbert, PB AF deCamp, Allan C. Rolland, Morgane Edlefsen, Paul T. Sanders-Buell, Eric Hall, Breana Magaret, Craig Fiore-Gartland, Andrew J. Juraska, Michal Graham, Barney S. Roederer, Mario Michael, Nelson L. Robb, Merlin L. McElrath, Juliana Tovanabutra, Sodsai Sobieszczyk, Magdalena E. Hammer, Scott M. Kim, Jerome H. Mullins, James I. Gilbert, Peter B. CA HVTN505 Sieve Anal Team TI Sieve Pressure toward the CD4 Binding Site of Env in HVTN 505 Breakthrough Infections SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [deCamp, Allan C.; Edlefsen, Paul T.; Magaret, Craig; Fiore-Gartland, Andrew J.; Juraska, Michal; McElrath, Juliana; Gilbert, Peter B.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Rolland, Morgane; Sanders-Buell, Eric; Michael, Nelson L.; Robb, Merlin L.; Tovanabutra, Sodsai] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA. [Rolland, Morgane; Sanders-Buell, Eric; Michael, Nelson L.; Robb, Merlin L.; Tovanabutra, Sodsai] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD USA. [Edlefsen, Paul T.; Hall, Breana; Mullins, James I.; Gilbert, Peter B.] Univ Washington, Seattle, WA 98195 USA. [Graham, Barney S.; Roederer, Mario] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Sobieszczyk, Magdalena E.; Hammer, Scott M.] Columbia Univ, Med Ctr, New York, NY 10027 USA. [Kim, Jerome H.] Int Vaccine Inst, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P12.03 BP 260 EP 260 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600477 ER PT J AU Rolland, M Tovanabutra, S Krebs, S Sanders-Buell, E Bose, M Kijak, G Sullivan, AMO Harbolick, E Bonar, L Owen, C Slike, B Dussupt, V Doria-Rose, N Mascola, J Nitayaphan, S Polonis, V Eller, LA Kim, J Michael, N Robb, M AF Rolland, Morgane Tovanabutra, Sodsai Krebs, Shelly Sanders-Buell, Eric Bose, Meera Kijak, Gustavo Sullivan, Anne Marie O. Harbolick, Elizabeth Bonar, Lydia Owen, Christopher Slike, Bonnie Dussupt, Vincent Doria-Rose, Nicole Mascola, John Nitayaphan, Sorachai Polonis, Vicky Eller, Leigh Anne Kim, Jerome Michael, Nelson Robb, Merlin TI Super-infection and Development of MPER-specific Neutralization Breadth in Subject 40512 from the Acute Infection Cohort RV217 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Rolland, Morgane; Tovanabutra, Sodsai; Krebs, Shelly; Sanders-Buell, Eric; Bose, Meera; Kijak, Gustavo; Sullivan, Anne Marie O.; Harbolick, Elizabeth; Bonar, Lydia; Owen, Christopher; Slike, Bonnie; Dussupt, Vincent; Eller, Leigh Anne; Robb, Merlin] Henry M Jackson Fdn Adv Mil Med, US Mil HIV Res Program, Bethesda, MD USA. [Doria-Rose, Nicole; Mascola, John] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Nitayaphan, Sorachai] Armed Forces Res Inst Med Sci AFRIMS, Bangkok, Thailand. [Polonis, Vicky; Michael, Nelson] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA. [Kim, Jerome] Int Vaccine Inst, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P12.20 BP 268 EP 268 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600494 ER PT J AU Houzet, L Perez-Losada, M Matusali, G Deleage, C Dereuddre-Bosquet, N Satie, AP Jegou, B Le Grand, R Keele, BF Crandall, KA Dejucq-Rainsford, N AF Houzet, Laurent Perez-Losada, Marcos Matusali, Giulia Deleage, Claire Dereuddre-Bosquet, Nathalie Satie, Anne-Pascale Jegou, Bernard Le Grand, Roger Keele, Brandon F. Crandall, Keith A. Dejucq-Rainsford, Nathalie TI Origin of AIDS Virus in Semen SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Houzet, Laurent; Matusali, Giulia; Deleage, Claire; Satie, Anne-Pascale; Jegou, Bernard; Dejucq-Rainsford, Nathalie] INSERM U 1085 IRSET, Rennes, France. [Perez-Losada, Marcos; Crandall, Keith A.] George Washington Univ, Computat Biol Inst, Washington, DC 20052 USA. [Dereuddre-Bosquet, Nathalie] CEA, DSV iMETI, Div Immunovirol, IDMIT, Fontenay Aux Roses, France. [Keele, Brandon F.] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P12.22LB BP 269 EP 269 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600496 ER PT J AU Trainor, N Cohen, S Vittinghoff, E Bacon, O Doblecki-Lewis, S Matheson, T Blue, RW Estrada, Y Coleman, ME Elion, R Chege, W Philip, SS Buchbinder, S Kolber, MA Liu, AY AF Trainor, Nikole Cohen, Stephanie Vittinghoff, Eric Bacon, Oliver Doblecki-Lewis, Susanne Matheson, Tim Blue, Robert Wilder Estrada, Yannine Coleman, Megan E. Elion, Richard Chege, Wairimu Philip, Susan S. Buchbinder, Susan Kolber, Michael A. Liu, Albert Y. TI Social Harms and Social Benefits among Participants Taking Prep in the US PrEP Demo Project SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Trainor, Nikole; Cohen, Stephanie; Matheson, Tim; Blue, Robert Wilder; Philip, Susan S.; Buchbinder, Susan] San Francisco Dept Publ Hlth, San Francisco, CA USA. [Cohen, Stephanie; Vittinghoff, Eric; Bacon, Oliver; Philip, Susan S.; Buchbinder, Susan; Liu, Albert Y.] Univ Calif San Francisco, San Francisco, CA USA. [Doblecki-Lewis, Susanne; Estrada, Yannine; Kolber, Michael A.] Univ Miami, Miller Sch Med, Coral Gables, FL 33124 USA. [Coleman, Megan E.] Whitman Walker Hlth, Washington, DC USA. [Elion, Richard] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA. [Chege, Wairimu] NIAID, Div AIDS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P15.18 BP 291 EP 291 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600537 ER PT J AU Sastry, M Xu, L Bhattacharya, S Nabel, GJ Bewley, CA Kwong, PD AF Sastry, Mallika Xu, Ling Bhattacharya, Shibani Nabel, Gary J. Bewley, Carole A. Kwong, Peter D. TI NMR Assignments and Dynamics of Ligand-free HIV-1 gp120 Outer Domain SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Sastry, Mallika; Xu, Ling; Nabel, Gary J.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD USA. [Bhattacharya, Shibani] New York Struct Biol Ctr, New York, NY USA. [Bewley, Carole A.] NIDDK, Lab Bioorgan Chem, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P16.04 BP 296 EP 296 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600547 ER PT J AU Arrode-Bruses, G Goode, D Frank, I Kleinbeck, K Byrareddy, S Arthos, J Grasperge, B Blanchard, J Gettie, A Zydowsky, T Martinelli, E AF Arrode-Bruses, Geraldine Goode, Diana Frank, Ines Kleinbeck, Kyle Byrareddy, Siddappa Arthos, James Grasperge, Brooke Blanchard, James Gettie, Agegnehu Zydowsky, Thomas Martinelli, Elena TI Inhibition of alpha(4)beta(7) Activation May be Necessary to Reduce Susceptibility to SIV: Differential Effect of an Agonist and an Allosteric Inhibitor SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Arrode-Bruses, Geraldine; Goode, Diana; Frank, Ines; Kleinbeck, Kyle; Zydowsky, Thomas; Martinelli, Elena] Populat Council, New York, NY USA. [Byrareddy, Siddappa] Univ Nebraska Med Ctr, Omaha, NE USA. [Arthos, James] NIAID, NIH, Bethesda, MD USA. [Grasperge, Brooke; Blanchard, James] Tulane Natl Primate Res Ctr, Covington, LA USA. [Gettie, Agegnehu] Aaron Diamond AIDS Res Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P18.12 BP 310 EP 310 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600574 ER PT J AU Soto, C Lemmin, T Stewart-Jones, GBE Kwong, PD AF Soto, Cinque Lemmin, Thomas Stewart-Jones, Guillaume B. E. Kwong, Peter D. TI Dynamics of the HIV-1 Glycan Shield SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Soto, Cinque; Stewart-Jones, Guillaume B. E.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Rockville, MD USA. [Lemmin, Thomas] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P19.09 BP 326 EP 326 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600605 ER PT J AU Matyas, GR Torres, OB Jalah, R Antoline, JFG Peachman, KK Beck, Z Rao, M Jacobson, AE Michael, NL Rice, KC Alving, CR AF Matyas, Gary R. Torres, Oscar B. Jalah, Rashmi Antoline, Joshua F. G. Peachman, Kristina K. Beck, Zoltan Rao, Mangala Jacobson, Arthur E. Michael, Nelson L. Rice, Kenner C. Alving, Carl R. TI Development of a Combination HIV-heroin Vaccine SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Matyas, Gary R.; Rao, Mangala; Michael, Nelson L.; Alving, Carl R.] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA. [Torres, Oscar B.; Jalah, Rashmi; Peachman, Kristina K.; Beck, Zoltan] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD USA. [Antoline, Joshua F. G.; Jacobson, Arthur E.; Rice, Kenner C.] NIDA, NIH, Bethesda, MD 20892 USA. [Antoline, Joshua F. G.; Jacobson, Arthur E.; Rice, Kenner C.] NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P19.13 BP 328 EP 328 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600608 ER PT J AU Chuang, GY Geng, H Pancera, M Acharya, P Chambers, M Druz, A Tsybovsky, Y Yang, YP Georgiev, I Gorman, J Joyce, MG McDermott, A Mascola, JR Kwong, PD AF Chuang, Gwo-Yu Geng, Hui Pancera, Marie Acharya, Priyamvada Chambers, Michael Druz, Aliaksandr Tsybovsky, Yaroslav Yang, Yongping Georgiev, Ivelin Gorman, Jason Joyce, M. Gordon McDermott, Adrian Mascola, John R. Kwong, Peter D. TI Increased Thermostability and Reduced CD4 Affinity of Structure-based Stabilized Prefusion Closed HIV-1 Env Trimer SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Chuang, Gwo-Yu; Geng, Hui; Pancera, Marie; Acharya, Priyamvada; Chambers, Michael; Druz, Aliaksandr; Tsybovsky, Yaroslav; Yang, Yongping; Georgiev, Ivelin; Gorman, Jason; Joyce, M. Gordon; McDermott, Adrian; Mascola, John R.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Rockville, MD USA. [Georgiev, Ivelin] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P19.16 BP 329 EP 329 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600611 ER PT J AU Stewart-Jones, GBE Soto, C Zhou, TQ Kwong, PD AF Stewart-Jones, Guillaume B. E. Soto, Cinque Zhou, Tongqing Kwong, Peter D. TI Identification of Dispersed Glycans on HIV-1 Env Trimer and Design of Related Immunogens SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Stewart-Jones, Guillaume B. E.; Soto, Cinque; Zhou, Tongqing; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P19.15 BP 329 EP 329 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600610 ER PT J AU Lagenaur, L Marcobal, A Nilsen, T Parks, T AF Lagenaur, Laurel Marcobal, Angela Nilsen, Trine Parks, Thomas TI Safety Evaluation of Live Biotherapeutics for Prevention of BV and HIV-1 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Lagenaur, Laurel; Marcobal, Angela; Nilsen, Trine; Parks, Thomas] Osel Inc, Mountain View, CA USA. [Lagenaur, Laurel] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P19.27 BP 335 EP 335 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600622 ER PT J AU Joyce, MG Georgiev, I Yang, YP Sastry, M Zhang, BS Cheng, C Chambers, M Tsybovsky, Y Aliaksandr, D Xu, K Zhou, TQ Chuang, GY Gorman, J Pancera, M Geng, H Kwon, YD Stewart-Jones, G Mc Dermott, A Mascola, J Kwong, P AF Joyce, M. Gordon Georgiev, Ivelin Yang, Yongping Sastry, Mallika Zhang Baoshan Cheng, Cheng Chambers, Michael Tsybovsky, Yaroslav Aliaksandr, Druz Xu, Kai Zhou, Tongqing Chuang Gwo-Yu Gorman, Jason Pancera, Marie Geng, Hui Kwon, Young-Do Stewart-Jones, Guillaume Mc Dermott, Adrian Mascola, John Kwong, Peter TI Designed HIV-1 Env Molecules from Multiple Clades That Display Structural and Antigenic Characteristics of the Mature Prefusion HIV-1 Env SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Joyce, M. Gordon; Georgiev, Ivelin; Yang, Yongping; Sastry, Mallika; Zhang Baoshan; Cheng, Cheng; Chambers, Michael; Tsybovsky, Yaroslav; Aliaksandr, Druz; Xu, Kai; Zhou, Tongqing; Chuang Gwo-Yu; Gorman, Jason; Pancera, Marie; Geng, Hui; Kwon, Young-Do; Stewart-Jones, Guillaume; Mc Dermott, Adrian; Mascola, John; Kwong, Peter] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P19.30 BP 336 EP 336 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600625 ER PT J AU Galkin, A Chen, YJ Guenaga, J O'Dell, S Chiang, CI Doria-Rose, N Mascola, JR Li, YX AF Galkin, Andrey Chen, Yajing Guenaga, Javier O'Dell, Sijy Chiang, Chi-I Doria-Rose, Nicole Mascola, John R. Li, Yuxing TI gp120-CD4i Antibody Complex as Immunogen SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Galkin, Andrey] Univ Maryland, Inst Biosci & Biotechnol Res, College Pk, MD 20742 USA. [Chen, Yajing] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Guenaga, Javier] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA. [O'Dell, Sijy; Doria-Rose, Nicole; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Chiang, Chi-I; Li, Yuxing] Univ Maryland, Inst Biosci & Biotechnol Res, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P19.47LB BP 345 EP 345 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600642 ER PT J AU Welles, H Bailer, R Mason, R Doria-Rose, N Nguyen, R O'Dell, S Hoxie, J Mascola, J Roederer, M AF Welles, Hugh Bailer, Robert Mason, Rosemarie Doria-Rose, Nicole Nguyen, Richard O'Dell, Siji Hoxie, James Mascola, John Roederer, Mario TI Isolation of SIV Env-specific Tier 2 Neutralizing Antibody from iMac-Delta D Immunized Macaque SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Welles, Hugh; Mason, Rosemarie; Doria-Rose, Nicole; Nguyen, Richard; O'Dell, Siji; Mascola, John; Roederer, Mario] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. George Washington Univ, Washington, DC 20052 USA. [Bailer, Robert] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Hoxie, James] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P19.50LB BP 346 EP 346 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600645 ER PT J AU Cheng, C Wanninger, T Joyce, MG Georgiev, I Chen, R Yang, YP Kong, WP Kwong, P Mascola, J AF Cheng, Cheng Wanninger, Timothy Joyce, M. Gordon Georgiev, Ivelin Chen, Rita Yang, Yongping Kong, Wing-Pui Kwong, Peter Mascola, John TI Membrane-anchored HIV-1 Envelope Immunogens with Native Trimer Antigenicity for DNA Vaccine SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Cheng, Cheng; Wanninger, Timothy; Joyce, M. Gordon; Georgiev, Ivelin; Chen, Rita; Yang, Yongping; Kong, Wing-Pui; Kwong, Peter; Mascola, John] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P19.52LB BP 347 EP 347 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600647 ER PT J AU Acharya, P Liu, QB Lusso, P Chuang, GY Druz, A Zhou, TQ Rice, WJ Wigge, C Carragher, B Potter, CS Kwong, PD AF Acharya, Priyamvada Liu, Qingbo Lusso, Paolo Chuang, Gwo-Yu Druz, Aliaksandr Zhou, Tongqing Rice, William J. Wigge, Christoph Carragher, Bridget Potter, Clinton S. Kwong, Peter D. TI Cryo-EM Structure of the First Contact of CD4 Receptor with HIV-1 Env SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Acharya, Priyamvada; Liu, Qingbo; Lusso, Paolo; Chuang, Gwo-Yu; Druz, Aliaksandr; Zhou, Tongqing; Kwong, Peter D.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Acharya, Priyamvada; Rice, William J.; Wigge, Christoph; Carragher, Bridget; Potter, Clinton S.] New York Struct Biol Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P19.54LB BP 348 EP 348 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600649 ER PT J AU Xu, K Liu, K Acharya, P Kong, R Druz, A Carragher, B Potter, CS Mascola, JR Kwong, PD AF Xu, Kai Liu, Kevin Acharya, Priyamvada Kong, Rui Druz, Alex Carragher, Bridget Potter, Clinton S. Mascola, John R. Kwong, Peter D. TI Study of Vaccine-Elicited HIV-1 Fusion Peptide-Targeting Antibody SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Xu, Kai; Liu, Kevin; Acharya, Priyamvada; Kong, Rui; Druz, Alex; Mascola, John R.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Carragher, Bridget; Potter, Clinton S.] Simons Electron Microscopy Ctr, Natl Resource Automated Mol Microscopy, New York, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P19.55LB BP 349 EP 349 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600650 ER PT J AU van der Straten, A Cheng, H Brown, ER Reddy, K Scheckter, R Soto-Torres, L Phillips-Palanee, T Baeten, J Mensch, B AF van der Straten, Ariane Cheng, Helen Brown, Elizabeth R. Reddy, Krishnaveni Scheckter, Rachel Soto-Torres, Lydia Phillips-Palanee, Thesla Baeten, Jared Mensch, Barbara CA MTN-020 ASPIRE Study Team TI Are Ring Worries Affecting Use? Findings from the MTN-020/ASPIRE Phase III Dapivirine Ring Trial SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [van der Straten, Ariane; Cheng, Helen] RTI Int, Womens Global Hlth Imperat, Res Triangle Pk, NC USA. [van der Straten, Ariane] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Brown, Elizabeth R.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Reddy, Krishnaveni; Phillips-Palanee, Thesla] Univ Witwatersrand, ZA-2050 Johannesburg, South Africa. [Scheckter, Rachel] FHI 360, Durham, NC USA. [Soto-Torres, Lydia] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. [Baeten, Jared] Univ Washington, Seattle, WA 98195 USA. [Mensch, Barbara] Populat Council, 1230 York Ave, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P24.03 BP 376 EP 376 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600700 ER PT J AU Scheckter, R McKinstry, L Balkus, J Beigi, R Kabwigu, S Noguchi, L Ndase, P Panchia, R Kintu, K Taljaard, M Mhlanga, F Nair, G Palanee-Phillips, T Moodley, J Piper, J Watts, H Pan, J Torjesen, K AF Scheckter, Rachel McKinstry, Laura Balkus, Jennifer Beigi, Rich Kabwigu, Samuel Noguchi, Lisa Ndase, Patrick Panchia, Ravindre Kintu, Kenneth Taljaard, Marthinette Mhlanga, Felix Nair, Gonasagrie Palanee-Phillips, Thesla Moodley, Jothi Piper, Jeanna Watts, Heather Pan, Jason Torjesen, Kristine TI Growth and Development of Infants Born to Women Enrolled in a Clinical Trial of Tenofovir-based Pre-exposure Prophylaxis for HIV Prevention SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Scheckter, Rachel; Torjesen, Kristine] FHI 360, Durham, NC USA. [McKinstry, Laura; Balkus, Jennifer; Pan, Jason] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Beigi, Rich] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Kabwigu, Samuel; Kintu, Kenneth] MU JHU, Kampala, Uganda. [Noguchi, Lisa] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Ndase, Patrick] PSI, Washington, DC USA. [Panchia, Ravindre] Perinatal HIV Res Unit, Soweto, South Africa. [Taljaard, Marthinette] Aurum Inst, Johannesburg, South Africa. [Mhlanga, Felix] UZ UCSF, Harare, Zimbabwe. [Nair, Gonasagrie] CAPRISA, Durban, South Africa. [Palanee-Phillips, Thesla] Wits Reprod Hlth & HIV Inst, Johannesburg, South Africa. [Moodley, Jothi] South African Med Res Council, Cape Town, South Africa. [Piper, Jeanna] NIH, Bldg 10, Bethesda, MD 20892 USA. [Watts, Heather] US Dept State, Washington, DC 20520 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P25.13 BP 395 EP 395 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600738 ER PT J AU Yang, YP Kwong, PD AF Yang, Yongping Kwong, Peter D. TI Throughput Screening of HIV-1 Broad Neutralizing Antibodies and Env Immunogens SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT Conference on HIV Research for Prevention (HIV R4P) CY OCT 17-20, 2016 CL Chicago, IL C1 [Yang, Yongping; Kwong, Peter D.] NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2016 VL 32 SU 1 MA P26.02 BP 400 EP 400 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EA6YH UT WOS:000386774600748 ER PT J AU Perkins, NJ Schisterman, EF AF Perkins, Neil J. Schisterman, Enrique F. TI RE: "RECEIVER OPERATING CHARACTERISTIC CURVE INFERENCE FROM A SAMPLE WITH A LIMIT OF DETECTION" Reply SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 [Perkins, Neil J.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA. RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA. EM schistee@mail.nih.gov NR 5 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 2016 VL 184 IS 7 BP 554 EP 554 DI 10.1093/aje/kww092 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA EA4AY UT WOS:000386552000009 PM 27620451 ER PT J AU Yoon, SS Dillon, CF Illoh, K Carroll, M AF Yoon, Sung Sug (Sarah) Dillon, Charles F. Illoh, Kachi Carroll, Margaret TI Trends in the Prevalence of Coronary Heart Disease in the US National Health and Nutrition Examination Survey, 2001-2012 SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID UNITED-STATES; BLOOD-PRESSURE; SELF-REPORTS; HYPERTENSION; ADULTS; MORTALITY; RISK; LIPOPROTEINS; POPULATION; VALIDITY AB Introduction: This study evaluated recent trends in the prevalence of coronary heart disease in the U.S. population aged >= 40 years. Methods: A total of 21,472 adults aged >= 40 years from the 2001-2012 National Health and Nutrition Examination Survey were included in the analysis. The analysis was conducted in 2015. Coronary heart disease included myocardial infarction, angina, and any other type of coronary heart disease, which were defined as a history of medical diagnosis of these specific conditions. Angina was also defined as currently taking anti-angina medication or having Rose Angina Questionnaire responses that scored with a Grade >= 1. Trends from 2001 to 2012 were analyzed overall, within demographic subgroups, and by major coronary heart disease risk factors. Results: Between 2001 and 2012, the overall prevalence of coronary heart disease significantly decreased from 10.3% to 8.0% (p-trend<0.05). The prevalence of angina significantly decreased from 7.8% to 5.5% and myocardial infarction prevalence decreased from 5.5% to 4.7% (p-trend <0.05 for both groups). Overall coronary heart disease prevalence significantly decreased among women, adults aged >60 years, non-Hispanic whites, non-Hispanic blacks, adults who did not complete high school, adults with more than a high school education, and adults who had health insurance (p-trend <0.05 for all groups). Conclusions: The overall prevalence of coronary heart disease including angina and myocardial infarction decreased significantly over the 12-year survey period. However, this reduction was seen mainly among persons without established coronary heart disease risk factors. There was no change in coronary heart disease prevalence among those with specific coronary heart disease risk factors. Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine C1 [Yoon, Sung Sug (Sarah)] NIH, Healthcare Delivery & Methodol IRG, Div AIDS Behav & Populat Sci, Ctr Sci Review, 6701 Rockledge Dr,Room 3152,MSC 7770, Bethesda, MD 20892 USA. [Dillon, Charles F.] CDC, Natl Ctr Hlth Stat, Hyattsville, MD USA. [Illoh, Kachi] US FDA, Off New Drugs Immediate Off, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Carroll, Margaret] CDC, Div Hlth & Nutr Examinat Surveys, Natl Ctr Hlth Stat, Hyattsville, MD USA. RP Yoon, SS (reprint author), NIH, Healthcare Delivery & Methodol IRG, Div AIDS Behav & Populat Sci, Ctr Sci Review, 6701 Rockledge Dr,Room 3152,MSC 7770, Bethesda, MD 20892 USA. EM sarah.yoon@nih.gov NR 39 TC 2 Z9 2 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2016 VL 51 IS 4 BP 437 EP 445 DI 10.1016/j.amepre.2016.02.023 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA EA7BX UT WOS:000386784200008 PM 27113539 ER PT J AU Choi, K Bernat, D AF Choi, Kelvin Bernat, Debra TI E-Cigarette Use Among Florida Youth With and Without Asthma SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID BRAIN-DEVELOPMENT; SMOKING; NICOTINE; TOBACCO AB Introduction: Although prevalence of youth e-cigarette use has increased dramatically, little is known about e-cigarette use among youth with asthma and how it differs by metropolitan status. This study assessed the prevalence of e-cigarette use among youth by asthma and metropolitan status and examined the associations between e-cigarette use, susceptibility to cigarette smoking, and asthma attack. Methods: High school student participants from the 2012 Florida Youth Tobacco Survey were included (N=36,085). Information on demographics, asthma status, ever and past 30-day use of e-cigarettes, cigarette smoking susceptibility, and having asthma attacks in the past 12 months were collected. Data were weighted to be representative of Florida high school students. Analyses were conducted in 2015. Results: Overall, prevalence of ever and past 30-day e-cigarette use among students who reported having asthma were 10.4% and 5.3%, respectively, higher than those without asthma (7.2% and 2.5%, respectively, p<0.01). Among students with asthma, e-cigarette use was more common among those in non-metropolitan and rural counties than those in metropolitan counties (p<0.05). Ever and past 30-day e-cigarette use was associated with cigarette smoking susceptibility among participants with asthma and those who never tried cigarettes (n=2,410; ever use, AOR=3.96, 95% CI=1.49, 10.56; past 30-day use, AOR=422.10, 95% CI=50.29, > 999.99). Past 30-day e-cigarette use was associated with having an asthma attack in the past 12 months among participants with asthma (n=5,865, p<0.01). Conclusions: E-cigarette use is more common among Florida high school youth with asthma and is associated with susceptibility to cigarette smoking. Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine C1 [Choi, Kelvin] Natl Inst Minor Hlth & Hlth Dispar, Div Intramural Res, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Bernat, Debra] Univ Maryland, Sch Publ Hlth, Dept Behav & Community Hlth, College Pk, MD 20742 USA. RP Choi, K (reprint author), Natl Inst Minor Hlth & Hlth Dispar, Div Intramural Res, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM kelvin.choi@nih.gov FU Division of Intramural Research, National Institute on Minority Health and Health Disparities, NIH; National Cancer Institute [R03 CA168411] FX Dr. Choi's effort is funded by the Division of Intramural Research, National Institute on Minority Health and Health Disparities, NIH. Dr. Bernat's effort is supported with a grant from the National Cancer Institute (R03 CA168411; D. Bernat, Principal Investigator). NR 26 TC 1 Z9 1 U1 4 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2016 VL 51 IS 4 BP 446 EP 453 DI 10.1016/j.amepre.2016.03.010 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA EA7BX UT WOS:000386784200009 PM 27085691 ER PT J AU McCarthy, AM Kim, JJ Beaber, EF Zheng, YY Burnett-Hartman, A Chubak, J Ghai, NR McLerran, D Breen, N Conant, EF Geller, BM Green, BB Klabunde, CN Inrig, S Skinner, CS Quinn, VP Haas, JS Schnall, M Rutter, CM Barlow, WE Corley, DA Armstrong, K Doubeni, CA AF McCarthy, Anne Marie Kim, Jane J. Beaber, Elisabeth F. Zheng, Yingye Burnett-Hartman, Andrea Chubak, Jessica Ghai, Nirupa R. McLerran, Dale Breen, Nancy Conant, Emily F. Geller, Berta M. Green, Beverly B. Klabunde, Carrie N. Inrig, Stephen Skinner, Celette Sugg Quinn, Virginia P. Haas, Jennifer S. Schnall, Mitchell Rutter, Carolyn M. Barlow, William E. Corley, Douglas A. Armstrong, Katrina Doubeni, Chyke A. CA PROSPR Consortium TI Follow-Up of Abnormal Breast and Colorectal Cancer Screening by Race/Ethnicity SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID OCCULT BLOOD-TEST; LOW-INCOME WOMEN; UNITED-STATES; CARE; MAMMOGRAPHY; DIAGNOSIS; QUALITY; PREDICTORS; TIME; IMPROVEMENT AB Introduction: Timely follow-up of abnormal tests is critical to the effectiveness of cancer screening, but may vary by screening test, healthcare system, and sociodemographic group. Methods: Timely follow-up of abnormal mammogram and fecal occult blood testing or fecal immunochemical tests (FOBT/FIT) were compared by race/ethnicity using Population-Based Research Optimizing Screening through Personalized Regimens consortium data. Participants were women with an abnormal mammogram (aged 40-75 years) or FOBT/FIT (aged 50-75 years) in 2010-2012. Analyses were performed in 2015. Timely follow-up was defined as colonoscopy <= 3 months following positive FOBT/ FIT; additional imaging or biopsy <= 3 months following Breast Imaging Reporting and Data System Category 0, 4, or 5 mammograms; or <= 9 months following Category 3 mammograms. Logistic regression was used to model receipt of timely follow-up adjusting for study site, age, year, insurance, and income. Results: Among 166,602 mammograms, 10.7% were abnormal; among 566,781 FOBT/FITs, 4.3% were abnormal. Nearly 96% of patients with abnormal mammograms received timely follow-up versus 68% with abnormal FOBT/FIT. There was greater variability in receipt of follow-up across healthcare systems for positive FOBT/FIT than for abnormal mammograms. For mammography, black women were less likely than whites to receive timely follow-up (91.8% vs 96.0%, OR=0.71, 95% CI=0.51, 0.97). For FOBT/FIT, Hispanics were more likely than whites to receive timely follow-up than whites (70.0% vs 67.6%, OR=1.12, 95% CI=1.04, 1.21). Conclusions: Timely follow-up among women was more likely for abnormal mammograms than FOBT/FITs, with small variations in follow-up rates by race/ethnicity and larger variation across healthcare systems. (C) 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved. C1 [McCarthy, Anne Marie; Armstrong, Katrina] Massachusetts Gen Hosp, Dept Med, 50 Staniford St,940F, Boston, MA 02114 USA. [Kim, Jane J.] Harvard TH Chan Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Beaber, Elisabeth F.; McLerran, Dale] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA. [Zheng, Yingye] Fred Hutchinson Canc Res Ctr, Dept Biostat, 1124 Columbia St, Seattle, WA 98104 USA. [Burnett-Hartman, Andrea] Fred Hutchinson Canc Res Ctr, Div Epidemiol, 1124 Columbia St, Seattle, WA 98104 USA. [Burnett-Hartman, Andrea] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [Chubak, Jessica; Green, Beverly B.] Grp Hlth Res Inst, Seattle, WA USA. [Ghai, Nirupa R.; Quinn, Virginia P.] Kaiser Permanente Southern Calif, Dept Res & Evaluat, Pasadena, CA USA. [Breen, Nancy] NCI, Hlth Syst & Intervent Res Branch, Bethesda, MD 20892 USA. [Conant, Emily F.; Schnall, Mitchell] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Geller, Berta M.] Univ Vermont, Dept Family Med, Burlington, VT USA. [Klabunde, Carrie N.] NIH, Off Dis Prevent, Bldg 10, Bethesda, MD 20892 USA. [Inrig, Stephen] Univ Texas Southwestern Med Ctr Dallas, Dept Hlth Policy & Hist Med, Dallas, TX 75390 USA. [Inrig, Stephen] Mt St Marys Univ, Dept Hlth Policy & Management, Los Angeles, CA USA. [Skinner, Celette Sugg] Univ Texas Southwestern Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Skinner, Celette Sugg] Univ Texas Southwestern Med Ctr Dallas, Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA. [Haas, Jennifer S.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Rutter, Carolyn M.] RAND Corp, Santa Monica, CA USA. [Barlow, William E.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Corley, Douglas A.] Kaiser Permanente Northern Calif, Dept Gastroenterol, Oakland, CA USA. [Doubeni, Chyke A.] Univ Penn, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. RP McCarthy, AM (reprint author), Massachusetts Gen Hosp, Dept Med, 50 Staniford St,940F, Boston, MA 02114 USA. EM amccarthy8@partners.org OI Inrig, Stephen/0000-0003-2091-5841 FU NIH/National Cancer Institute PROSPR program [U54CA163262, U54CA163261, U54CA163308, U54CA163313, U54CA163303, U54CA163307, U54CA164336, U01CA163304] FX This work was funded by the NIH/National Cancer Institute PROSPR program, grant numbers: Kaiser Foundation Research Institute U54CA163262, Group Health Research Institute U54CA163261, Parkland UT Southwestern U54CA163308, University of Pennsylvania U54CA163313, University of Vermont U54CA163303, Geisel School of Medicine at Dartmouth and Brigham and Women's Hospital U54CA163307, University of New Mexico U54CA164336, Fred Hutchinson Cancer Research Center U01CA163304. NR 32 TC 1 Z9 1 U1 8 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2016 VL 51 IS 4 BP 507 EP 512 DI 10.1016/j.amepre.2016.03.017 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA EA7BX UT WOS:000386784200016 PM 27132628 ER PT J AU Sandhu, PK Elder, R Patel, M Saraiya, M Holman, DM Perna, F Smith, RA Buller, D Sinclair, C Reeder, A Makin, J McNoe, B Glanz, K AF Sandhu, Paramjit K. Elder, Randy Patel, Mona Saraiya, Mona Holman, Dawn M. Perna, Frank Smith, Robert A. Buller, David Sinclair, Craig Reeder, Anthony Makin, Jennifer McNoe, Bronwen Glanz, Karen CA Community Preventive Serv TI Community-wide Interventions to Prevent Skin Cancer Two Community Guide Systematic SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID PROMOTE SUN PROTECTION; MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; ULTRAVIOLET-RADIATION; DYSPLASTIC NEVI; UNITED-STATES; RISK-FACTORS; AUSTRALIA; METAANALYSIS; PREVALENCE AB Context: Skin cancer is a preventable and commonly diagnosed cancer in the U.S. Excessive ultraviolet radiation exposure is a known cause of skin cancer. This article presents updated results of two types of interventions evaluated in a previously published Community Guide systematic review: multicomponent community-wide interventions and mass media interventions when used alone. Evidence acquisition: Studies assessing multicomponent community-wide and mass media interventions to prevent skin cancer by reducing ultraviolet radiation exposure were evaluated using Community Guide systematic review methods. Relevant studies published between 1966 and 2013 were included and analyzed for this review. Evidence synthesis: Seven studies evaluating the effectiveness of multicomponent community-wide interventions showed a median increase in sunscreen use of 10.8 (interquartile interval=7.3, 23.2) percentage points, a small decrease in ultraviolet radiation exposure, a decrease in indoor tanning device use of 4.0 (95% CI=2.5, 5.5) percentage points, and mixed results for other protective behaviors. Four studies evaluating the effectiveness of mass media interventions found that they generally led to improved ultraviolet protection behaviors among children and adults. Conclusions: The available evidence showed that multicomponent community-wide interventions are effective in reducing the deleterious effects of ultraviolet radiation exposure by increasing sunscreen use. There was, however, insufficient evidence to determine the effectiveness of mass media interventions alone in reducing ultraviolet radiation exposure and increasing ultraviolet protection behaviors, indicating a continuing need for more research in this field to improve assessment of effectiveness. Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine. C1 [Sandhu, Paramjit K.; Elder, Randy; Patel, Mona] Ctr Dis Control & Prevent CDC, Community Guide Branch, Div Publ Hlth Informat Disseminat, Atlanta, GA USA. [Saraiya, Mona; Holman, Dawn M.] CDC, Div Canc Prevent & Control, Atlanta, GA 30333 USA. [Perna, Frank] NCI, NIH, Bethesda, MD 20892 USA. [Smith, Robert A.] Amer Canc Soc, Atlanta, GA 30329 USA. [Buller, David] Klein Buendel, Lakewood, CO USA. [Sinclair, Craig] Canc Council Victoria, Ctr Behav Res Canc, Melbourne, Vic, Australia. [Reeder, Anthony; McNoe, Bronwen] Univ Otago, Dept Prevent & Social Med, Canc Soc Social & Behav Res Unit, Dunedin, New Zealand. [Makin, Jennifer] Univ Tasmania, Menzies Res Inst, Hobart, Tas 7001, Australia. [Glanz, Karen] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Glanz, Karen] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. RP Sandhu, PK (reprint author), Ctr Dis Control & Prevent CDC, Lab Res & Evaluat Branch, 1600 Clifton Rd,Mailstop E-69, Atlanta, GA 30329 USA. EM psandhu@cdc.gov FU Intramural CDC HHS [CC999999] NR 43 TC 1 Z9 1 U1 5 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2016 VL 51 IS 4 BP 531 EP 539 DI 10.1016/j.amepre.2016.03.020 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA EA7BX UT WOS:000386784200021 PM 27647053 ER PT J AU Rigotti, NA Stoney, CM AF Rigotti, Nancy A. Stoney, Catherine M. TI CHARTing the Future Course of Tobacco-Cessation Interventions for Hospitalized Smokers SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article C1 [Rigotti, Nancy A.] Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Rigotti, Nancy A.] Harvard Med Sch, Boston, MA USA. [Stoney, Catherine M.] NHLBI, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, 50 Staniford St,914, Boston, MA 02114 USA. EM nrigotti@partners.org FU NIH/National Heart, Lung, and Blood Institute [R01-HL11821] FX Dr. Rigotti was supported by NIH/National Heart, Lung, and Blood Institute grant number R01-HL11821, receives royalties from UpToDate, Inc., and has received travel expenses from Pfizer, Inc., to attend consultant meetings for which she received no honorarium. No other financial disclosures were reported by the authors of this paper. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH or the U.S. Government. NR 10 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2016 VL 51 IS 4 BP 549 EP 550 DI 10.1016/j.amepre.2016.07.012 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA EA7BX UT WOS:000386784200024 PM 27647055 ER PT J AU Fellows, JL Mularski, RA Leo, MC Bentz, CJ Waiwaiole, LA Francisco, MC Funkhouser, K Stoney, CM AF Fellows, Jeffrey L. Mularski, Richard A. Leo, Michael C. Bentz, Charles J. Waiwaiole, Lisa A. Francisco, Melanie C. Funkhouser, Kimberly Stoney, Catherine M. TI Referring Hospitalized Smokers to Outpatient Quit Services A Randomized Trial SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID SMOKING-CESSATION INTERVENTION; CIGARETTE-SMOKING; HEART-DISEASE; SYSTEM; CARE; PERFORMANCE; MODEL AB Introduction: Linking outpatient cessation services to bedside counseling for hospitalized smokers can improve long-run quit rates. Adding an assisted referral (AR) offer to a tobacco treatment specialist consult service fits the team approach to care in U.S. hospitals. Design: A two-arm patient-randomized trial tested the effectiveness of adding an AR offer to outpatient smoking-cessation services and interactive voice recognition (AR+IVR) follow-up to a usual care (UC) tobacco-cessation consult for hospitalized smokers. Setting/participants: Over 24 months (November 2011-November 2013), 898 hospitalized adult smokers interested in quitting smoking were recruited from three large hospitals in the Portland, Oregon, area: an integrated group model HMO (n=622), a community hospital (n=195), and an academic health center (n=81). Intervention: Tobacco treatment specialists identified smokers and provided an intensive bedside tobacco use assessment and cessation consultation (UC). AR+IVR recipients also received proactive ARs to available outpatient counseling programs and medications, and linked patients to a tailored IVR telephone follow-up system. Main outcome measures: The primary outcome was self-reported 30-day abstinence at 6-month follow-up. Secondary outcomes included self-reported and continuous abstinence and biochemically confirmed 7-day abstinence at 6 months. Follow-up was completed in September 2014; data were analyzed in 2015. Results: A total of 597 and 301 hospitalized smokers were randomized to AR+IVR and UC, respectively. AR+IVR and UC recipients received 19.3 and 17.0 minutes of bedside counseling (p=0.372), respectively. Most (58%) AR+IVR patients accepted referrals for counseling, 43% accepted medications, and 28% accepted both. Self-reported 30-day abstinence for AR+IVR (17.9%) and UC (17.3%) were not statistically significant (p=0.569). Differences in 7-day, continuous, and biochemically confirmed abstinence by treatment group also were insignificant, overall and adjusting for site. Conclusions: Adding an AR to outpatient counseling and medications did not increase cigarette abstinence at 6 months compared to UC alone. (C) 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved. C1 [Fellows, Jeffrey L.; Mularski, Richard A.; Leo, Michael C.; Waiwaiole, Lisa A.; Francisco, Melanie C.; Funkhouser, Kimberly] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. [Bentz, Charles J.] Legacy Hlth Syst, Tobacco Cessat & Prevent, Portland, OR USA. [Stoney, Catherine M.] NHLBI, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Fellows, JL (reprint author), Kaiser Permanente Northwest, Ctr Hlth Res, 3800 N Interstate Ave, Portland, OR 97227 USA. EM jeffrey.fellows@kpchr.org FU National Heart, Lung, and Blood Institute [U01 HL105231, NCT01236079] FX Funding was provided by the National Heart, Lung, and Blood Institute (U01 HL105231; clinical trials registration, NCT01236079). The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH or the U.S. Government. NR 35 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2016 VL 51 IS 4 BP 609 EP 619 DI 10.1016/j.amepre.2016.06.014 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA EA7BX UT WOS:000386784200030 PM 27647061 ER PT J AU Cruvinel, E Richter, KP Stoney, C Duffy, S Fellows, J Harrington, KF Rigotti, NA Sherman, S Tindle, HA Shireman, TI Shelley, D Waiwaiole, L Cummins, S AF Cruvinel, Erica Richter, Kimber P. Stoney, Catherine Duffy, Sonia Fellows, Jeffrey Harrington, Kathleen F. Rigotti, Nancy A. Sherman, Scott Tindle, Hilary A. Shireman, Theresa I. Shelley, Donna Waiwaiole, Lisa Cummins, Sharon TI CHARTing a Path to Pragmatic Tobacco Treatment Research SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID TRIALS; PRECIS AB Introduction: It is important to consider the degree to which studies are explanatory versus pragmatic to understand the implications of their findings for patients, healthcare professionals, and policymakers. Pragmatic trials test the effectiveness of interventions in real-world conditions; explanatory trials test for efficacy under ideal conditions. The Consortium of Hospitals Advancing Research on Tobacco (CHART) is a network of seven NIH-funded trials designed to identify effective programs that can be widely implemented in routine clinical practice. Methods: A cross-sectional analysis of CHART trial study designs was conducted to place each study on the pragmatic-explanatory continuum. After reliability training, six raters independently scored each CHART study according to ten PRagmatic Explanatory Continuum Indicator Summary (PRECIS) dimensions, which covered participant eligibility criteria, intervention flexibility, practitioner expertise, follow-up procedures, participant compliance, practitioner adherence, and outcome analyses. Means and SDs were calculated for each dimension of each study, with lower scores representing more pragmatic elements. Results were plotted on "spoke and wheel" diagrams. The rating process and analyses were performed in October 2014 to September 2015. Results: All seven CHART trials tended toward the pragmatic end of the spectrum, although there was a range from 0.76 (SD = 0.23) to 1.85 (SD = 0.58). Most studies included some explanatory design elements. Conclusions: CHART findings should be relatively applicable to clinical practice. Funders and reviewers could integrate PRECIS criteria into their guidelines to better facilitate pragmatic research. CHART study protocols, coupled with scores reported here, may help readers improve the design of their own pragmatic trials. (C) 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved. C1 [Cruvinel, Erica] Univ Fed Juiz de Fora, Dept Psychol, Juiz De Fora, MG, Brazil. [Richter, Kimber P.] Univ Kansas, Med Ctr, Dept Prevent Med & Publ Hlth, Kansas City, KS 66103 USA. [Richter, Kimber P.] Univ Kansas, Med Ctr, Ctr Canc, Kansas City, KS 66103 USA. [Stoney, Catherine] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. [Duffy, Sonia] Ohio State Univ, Coll Nursing, Columbus, OH 43210 USA. [Duffy, Sonia] Dept Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Fellows, Jeffrey; Waiwaiole, Lisa] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. [Harrington, Kathleen F.] Univ Alabama Birmingham, Dept Med, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA. [Rigotti, Nancy A.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. [Rigotti, Nancy A.] Harvard Med Sch, Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA USA. [Sherman, Scott] NYU, Sch Med, Dept Populat Hlth Med, New York, NY USA. [Sherman, Scott] NYU, Sch Med, Dept Med, New York, NY USA. [Sherman, Scott] NYU, Sch Med, Dept Psychiat, New York, NY USA. [Tindle, Hilary A.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. [Shireman, Theresa I.] Brown Univ, Dept Hlth Serv Policy & Practice, Providence, RI 02912 USA. [Shelley, Donna] NYU, Sch Med, Dept Populat Med, New York, NY USA. [Cummins, Sharon] Univ Calif San Diego, Dept Family Med & Publ Hlth, San Diego, CA 92103 USA. RP Cruvinel, E (reprint author), Univ Fed Juiz de Fora, Dept Psychol, Ctr Res Intervent & Evaluat Alcohol & Other Drugs, Juiz De Fora, MG, Brazil. EM ecruvinel@yahoo.com.br OI Sherman, Scott/0000-0003-1752-7303 FU Foundation for Research Support of Minas Gerais (FAPEMIG); National Council for Scientific and Technological Development (CNPq); Coordination for the Improvement of Higher Education Personnel (CAPES) of Brazil; National Heart, Lung, and Blood Institute [U01 HL105232-01] FX The authors thank Niaman Nazir, MBBS, MPH, for assistance with formatting the spoke and wheel diagrams. This work was supported by the National Heart, Lung, and Blood Institute (U01 HL105232-01) and the Foundation for Research Support of Minas Gerais (FAPEMIG), National Council for Scientific and Technological Development (CNPq), and Coordination for the Improvement of Higher Education Personnel (CAPES) of Brazil. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute; NIH; or the government of Brazil. The study sponsor had no role in study design; collection, analysis, or interpretation of data; writing the report; or the decision to submit the report for publication. NR 18 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2016 VL 51 IS 4 BP 630 EP 636 DI 10.1016/j.amepre.2016.05.025 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA EA7BX UT WOS:000386784200032 PM 27647063 ER PT J AU Chambers, DA Norton, WE AF Chambers, David A. Norton, Wynne E. TI The Adaptome Advancing the Science of Intervention Adaptation SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID PREVENTION INTERVENTIONS; THERAPIST ADHERENCE; MENTAL-HEALTH; IMPLEMENTATION; FIDELITY; TECHNOLOGIES; BEHAVIOR; OUTCOMES AB In the past few decades, prevention scientists have developed and tested a range of interventions with demonstrated benefits on child and adolescent cognitive, affective, and behavioral health. These evidence-based interventions offer promise of population-level benefit if accompanied by findings of implementation science to facilitate adoption, widespread implementation, and sustainment. Though there have been notable examples of successful efforts to scale up interventions, more work is needed to optimize benefit. Although the traditional pathway from intervention development and testing to implementation has served the research community well-allowing for a systematic advance of evidence-based interventions that appear ready for implementation-progress has been limited by maintaining the hypothesis that evidence generation must be complete prior to implementation. This sets up the challenging dichotomy between fidelity and adaptation and limits the science of adaptation to findings from randomized trials of adapted interventions. The field can do better. This paper argues for the development of strategies to advance the science of adaptation in the context of implementation that would more comprehensively describe the needed fit between interventions and their settings, and embrace opportunities for ongoing learning about optimal intervention delivery over time. Efforts to build the resulting adaptome (pronounced "adapt-ohm") will include the construction of a common data platform to house systematically captured information about variations in delivery of evidence-based interventions across multiple populations and contexts, and provide feedback to intervention developers, as well as the implementation research and practice communities. Finally, the article identifies next steps to jumpstart adaptome data platform development. Published by Elsevier Inc. C1 [Chambers, David A.; Norton, Wynne E.] NCI, Div Canc Control & Populat Sci, 9609 Med Ctr Dr, Bethesda, MD 20850 USA. RP Chambers, DA (reprint author), NCI, Div Canc Control & Populat Sci, 9609 Med Ctr Dr, Bethesda, MD 20850 USA. EM dchamber@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 35 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2016 VL 51 IS 4 SU 2 BP S124 EP S131 DI 10.1016/j.amepre.2016.05.011 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA EA7BM UT WOS:000386783100004 PM 27371105 ER PT J AU Harding, FM Hingson, RW Klitzner, M Mosher, JF Brown, J Vincent, RM Dahl, E Cannon, CL AF Harding, Frances M. Hingson, Ralph W. Klitzner, Michael Mosher, James F. Brown, Jorielle Vincent, Robert M. Dahl, Elizabeth Cannon, Carol L. TI Underage Drinking A Review of Trends and Prevention Strategies SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Review ID ALCOHOL-RELATED MORTALITY; KEG REGISTRATION LAWS; STUDENTS AGES 18-24; COLLEGE-STUDENTS; CONTROL POLICIES; COMMUNITY TRIAL; BINGE DRINKING; UNITED-STATES; FATAL CRASHES; YOUTH ACCESS AB Underage drinking and its associated problems have profound negative consequences for underage drinkers themselves, their families, their communities, and society as a whole, and contribute to a wide range of costly health and social problems. There is increased risk of negative consequences with heavy episodic or binge drinking. Alcohol is a factor related to approximately 4,300 deaths among underage youths in the U.S. every year. Since the mid-1980s, the nation has launched aggressive underage drinking prevention efforts at the federal, state, and local levels, and national epidemiologic data suggest that these efforts are having positive effects. For example, since 1982, alcohol-related traffic deaths among youth aged 16-20 years have declined by 79%. Evidence-based or promising strategies for reducing underage drinking include those that limit the physical, social, and economic availability of alcohol to youth, make it illegal for drivers aged <21 years to drive after drinking, and provide mechanisms for early identification of problem drinkers. Strategies may be implemented through a comprehensive prevention approach including policies and their enforcement, public awareness and education, action by community coalitions, and early brief alcohol intervention and referral programs. This paper focuses on underage drinking laws and their enforcement because these constitute perhaps the most fundamental component of efforts to limit youth access to and use of alcohol. Published by Elsevier Inc. C1 [Harding, Frances M.; Brown, Jorielle; Vincent, Robert M.] SAMHSA, CSAP, Rockville, MD USA. [Hingson, Ralph W.] NIAAA, Div Epidemiol & Prevent Res, Bethesda, MD USA. [Klitzner, Michael; Dahl, Elizabeth; Cannon, Carol L.] CDM Grp Inc, Bethesda, MD USA. [Mosher, James F.] Alcohol Policy Consultat, Felton, CA USA. RP Vincent, RM (reprint author), Subst Abuse & Mental Hlth Serv Adm, CSAP, 5600 Fishers Lane, Rockville, MD 20857 USA. EM robert.vincent@samhsa.hhs.gov FU Substance Abuse and Mental Health Services Administration [HHSS28320070008I/HHSS28342001T] FX This work was funded by the Substance Abuse and Mental Health Services Administration under Contract number HHSS28320070008I/HHSS28342001T. NR 96 TC 1 Z9 1 U1 17 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2016 VL 51 IS 4 SU 2 BP S148 EP S157 DI 10.1016/j.amepre.2016.05.020 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA EA7BM UT WOS:000386783100007 PM 27476384 ER PT J AU Bissa, M Quaglino, E Zanotto, C Illiano, E Rolih, V Pacchioni, S Cavallo, F Morghen, CD Radaelli, A AF Bissa, Massimiliano Quaglino, Elena Zanotto, Carlo Illiano, Elena Rolih, Valeria Pacchioni, Sole Cavallo, Federica Morghen, Carlo De Giuli Radaelli, Antonia TI Protection of mice against the highly pathogenic VVIHD-J by DNA and fowlpox recombinant vaccines, administered by electroporation and intranasal routes, correlates with serum neutralizing activity SO ANTIVIRAL RESEARCH LA English DT Article DE Recombinant vaccines; Fowlpox virus; Prime/boost; OPXV vaccine; L1R, A27L, A33R, B5R VV genes; Intranasal mucosal vaccination ID PRIME-BOOST IMMUNIZATION; SMALLPOX VACCINE; ANTIBODY-RESPONSES; NONHUMAN-PRIMATES; VIRUS CHALLENGE; T-CELLS; MONKEYPOX VIRUS; MUCOSAL; IMMUNITY; INFECTION AB The control of smallpox was achieved using live vaccinia virus (VV) vaccine, which successfully eradicated the disease worldwide. As the variola virus no longer exists as a natural infection agent, mass vaccination was discontinued after 1980. However, emergence of smallpox outbreaks caused by accidental or deliberate release of variola virus has stimulated new research for second-generation vaccine development based on attenuated VV strains. Considering the closely related animal poxviruses that also arise as zoonoses, and the increasing number of unvaccinated or immunocompromised people, a safer and more effective vaccine is still required. With this aim, new vectors based on avian poxviruses that cannot replicate in mammals should improve the safety of conventional vaccines, and protect from zoonotic orthopoxvirus diseases, such as cowpox and monkeypox. In this study, DNA and fowlpox (FP) recombinants that expressed the VV L1R, A27L, A33R, and B5R genes were generated (4DNAmix, 4FPmix, respectively) and tested in mice using novel administration routes. Mice were primed with 4DNAmix by electroporation, and boosted with 4FPmix applied intranasally. The lethal VVIHD-J strain was then administered by intranasal challenge. All of the mice receiving 4DNAmix followed by 4FPmix, and 20% of the mice immunized only with 4FPmix, were protected. The induction of specific humoral and cellular immune responses directly correlated with this protection. In particular, higher anti-A27 antibodies and IFN gamma-producing T lymphocytes were measured in the blood and spleen of the protected mice, as compared to controls. VVIHD-J neutralizing antibodies in sera from the protected mice suggest that the prime/boost vaccination regimen with 4DNAmix plus 4FPmix may be an effective and safe mode to induce protection against smallpox and poxvirus zoonotic infections. The electroporation/intranasal administration routes contributed to effective immune responses and mouse survival. (C) 2016 Elsevier B.V. All rights reserved. C1 [Bissa, Massimiliano; Illiano, Elena; Pacchioni, Sole; Radaelli, Antonia] Univ Milan, Dept Pharmacol & Biomol Sci, Via Balzaretti 9, I-20133 Milan, Italy. [Quaglino, Elena; Rolih, Valeria; Cavallo, Federica] Univ Turin, Dept Mol Biotechnol & Hlth Sci, Ctr Mol Biotechnol, Via Nizza 52, I-10126 Turin, Italy. [Zanotto, Carlo; Morghen, Carlo De Giuli] Univ Milan, Dept Med Biotechnol & Translat Med, Via Vanvitelli 32, I-20129 Milan, Italy. [Morghen, Carlo De Giuli] Catholic Univ Our Lady Good Counsel, Tirana, Albania. [Radaelli, Antonia] Univ Milan, Inst Neurosci, Cellular & Mol Pharmacol Sect, CNR, Via Vanvitelli 32, I-20129 Milan, Italy. [Bissa, Massimiliano] NCI, NIH, Basic Res Labs, Bethesda, MD 20892 USA. RP Morghen, CD; Radaelli, A (reprint author), Univ Milan, Lab Mol Virol & Recombinant Vaccine Dev, Dept Pharmacol & Biomol Sci, Via Vanvitelli 32, I-20129 Milan, Italy. EM massimiliano.bissa@nih.gov; elena.quaglino@unito.it; carlo.zanotto@unimi.it; elena.illiano@unimi.it; valeria.rolih@unito.it; sol83@libero.it; federica.cavallo@unito.it; carlo.degiulimorghen@unimi.it; antonia.radaelli@unimi.it RI Cavallo, Federica/C-5666-2011; OI Cavallo, Federica/0000-0003-4571-1060; Quaglino, Elena/0000-0002-8151-9124 FU University of Milano Transition Grant [18498, CUP G42I14001030001]; Fondazione Ricerca Molinette Onlus and Fondazione CRT, Torino, Italy [2015-2518] FX This work was partially founded by the University of Milano Transition Grant, code no. 18498, CUP G42I14001030001 and by grants to FC from Fondazione Ricerca Molinette Onlus and Fondazione CRT, Torino, Italy, grant no. 2015-2518. The following reagents were obtained through the NIH Biodefense and Emerging Infections Research Resources Repository, (NIAID, NIH): vaccinia virus (WR) L1R protein with C-terminal histidine tag, recombinant from baculovirus, NR-2625; vaccinia virus (WR) A27L protein with C-terminal histidine tag, recombinant from baculovirus, NR-2622; vaccinia virus (WR) A33R protein with C-terminal histidine tag, recombinant from baculovirus, NR-545; vaccinia virus (WR) B5R protein with N-terminal histidine tag, recombinant from baculovirus, NR-546. The authors also thank Dr. Christopher P. Berrie for editorial assistance with the manuscript. NR 66 TC 0 Z9 0 U1 5 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 EI 1872-9096 J9 ANTIVIR RES JI Antiviral Res. PD OCT PY 2016 VL 134 BP 182 EP 191 DI 10.1016/j.antiviral.2016.09.002 PG 10 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA EA9SA UT WOS:000386983800021 PM 27637905 ER PT J AU Hartman, TL Yang, L Helfrick, AN Hassink, M Shank, NI Rosenker, KG Scerba, MT Saha, M Hughes, E Wang, AQ Xu, X Gupta, P Buckheit, RW Appella, DH AF Hartman, T. L. Yang, L. Helfrick, A. N. Hassink, M. Shank, N. I. Rosenker, K. George Scerba, M. T. Saha, M. Hughes, E. Wang, A. Q. Xu, X. Gupta, P. Buckheit, R. W., Jr. Appella, D. H. TI Preclinical evaluation of a mercaptobenzamide and its prodrug for NCp7-targeted inhibition of human immunodeficiency virus SO ANTIVIRAL RESEARCH LA English DT Article ID TYPE-1 NUCLEOCAPSID PROTEIN; ZINC-FINGER INHIBITORS; ANTI-HIV AGENTS; VIRAL-DNA; REPLICATION; TARGET; BINDING; NCP7; RNA; INACTIVATION AB Although the effective use of highly active antiretroviral therapy results in the suppression of virus production in infected individuals, it does not eliminate the infection and low level virus production in cells harboring virus in sanctuary sites. Thus, the continued search for new antiretroviral agents with unique and different mechanisms of HIV inhibition remains critical, and compounds that can reduce the level of virus production from cells already infected with HIV, as opposed to preventing de novo infection, would be of great benefit. A mercaptobenzamide (MDH-1-38) and its prodrug (NS1040) are being developed as potential therapeutic compounds targeting the zinc finger of HIV nucleocapsid. In the presence of esterase enzymes, NS1040 is designed to be converted to MDH-1-38 which has antiviral activity. While we presume that NS1040 is rapidly converted to MDH-1-38 in all experiments, the two compounds were tested side-by-side to determine whether the presence of a prodrug affects the antiviral activity or mechanism of action. The two compounds were evaluated against a panel of HIV-1 clinical isolates in human PBMCs and monocyte-macrophages and yielded EC50 values ranging from 0.7 to 13 mu M with no toxicity up to 100 mu M. MDH-1-38 and NS1040 remained equally active in human PBMCs in the presence of added serum proteins as well as against HIV-1 isolates resistant to reverse transcriptase, integrase or protease inhibitors. Cell-based and biochemical mechanism of antiviral action assays demonstrated MDH-1-38 and NS1040 were virucidal at concentrations of 15 and 50 mu M, respectively. Cell to cell transmission of HIV in multiple passages was significantly reduced in CEM-SS and human PBMCs by reducing progeny virus infectivity at compound concentrations greater than 2 mu M. The combination of either MDH-1-38 or NS1040 with other FDA-approved HIV drugs yielded additive to synergistic antiviral interactions with no evidence of antiviral antagonism or synergistic toxicity. Serial dose escalation was used in attempts to select for HIV strains resistant to MDH-1-38 and NS1040. Virus at several passages failed to replicate in cells treated at increased compound concentrations, which is consistent with the proposed mechanism of action of the virus inactivating compounds. Through 14 passages, resistance to the compounds has not been achieved. Most HIV inhibitors with mechanism of antiviral action targeting a viral protein would have selected for a drug resistant virus within 14 passages. These studies indicate that these NCp7-targeted compounds represent new potent anti-HIV drug candidates which could be effectively used in combination with all approved anti-HIV drugs. (C) 2016 Published by Elsevier B.V. C1 [Hartman, T. L.; Yang, L.; Helfrick, A. N.; Buckheit, R. W., Jr.] ImQuest Biosci Inc, 7340 Execut Way,Suite R, Frederick, MD 21704 USA. [Hassink, M.; Shank, N. I.; Rosenker, K. George; Scerba, M. T.; Saha, M.; Gupta, P.; Appella, D. H.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Hughes, E.; Wang, A. Q.; Xu, X.] NIH, NCATS, Bldg 10, Bethesda, MD 20892 USA. RP Buckheit, RW (reprint author), ImQuest Biosci Inc, 7340 Execut Way,Suite R, Frederick, MD 21704 USA.; Appella, DH (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM rbuckheit@imquestbio.com; appellad@niddk.nih.gov FU Intramural Research Program of NIDDK, NIH [DK075135-01] FX This work was supported in part by funding from the Intramural Research Program of NIDDK (DK075135-01), NIH. Toxicity studies in rats were performed under contract by Pharmaron (Irvine, CA). NR 34 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 EI 1872-9096 J9 ANTIVIR RES JI Antiviral Res. PD OCT PY 2016 VL 134 BP 216 EP 225 DI 10.1016/j.antiviral.2016.08.022 PG 10 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA EA9SA UT WOS:000386983800024 PM 27568924 ER PT J AU Levin, GV Straat, PA AF Levin, Gilbert V. Straat, Patricia Ann TI The Case for Extant Life on Mars and Its Possible Detection by the Viking Labeled Release Experiment SO ASTROBIOLOGY LA English DT Review ID D-AMINO ACIDS; GALE CRATER; MARTIAN SOIL; PERCHLORATE; LANDER; MICROORGANISMS; ENVIRONMENTS; METABOLISM; REACTIVITY; BACTERIA AB The 1976 Viking Labeled Release (LR) experiment was positive for extant microbial life on the surface of Mars. Experiments on both Viking landers, 4000 miles apart, yielded similar, repeatable, positive responses. While the authors eventually concluded that the experiment detected martian life, this was and remains a highly controversial conclusion. Many believe that the martian environment is inimical to life and the LR responses were nonbiological, attributed to an as-yet-unidentified oxidant (or oxidants) in the martian soil. Unfortunately, no further metabolic experiments have been conducted on Mars. Instead, follow-on missions have sought to define the martian environment, mostly searching for signs of water. These missions have collected considerable data regarding Mars as a habitat, both past and present. The purpose of this article is to consider recent findings about martian water, methane, and organics that impact the case for extant life on Mars. Further, the biological explanation of the LR and recent nonbiological hypotheses are evaluated. It is concluded that extant life is a strong possibility, that abiotic interpretations of the LR data are not conclusive, and that, even setting our conclusion aside, biology should still be considered as an explanation for the LR experiment. Because of possible contamination of Mars by terrestrial microbes after Viking, we note that the LR data are the only data we will ever have on biologically pristine martian samples. Key Words: Extant life on MarsViking Labeled Release experimentAstrobiologyExtraterrestrial lifeMars. Astrobiology 16, 798-810. C1 [Levin, Gilbert V.] Arizona State Univ, Tempe, AZ USA. [Straat, Patricia Ann] NIH, Bldg 10, Bethesda, MD 20892 USA. [Levin, Gilbert V.; Straat, Patricia Ann] Biospherics Inc, Rockville, MD USA. RP Levin, GV (reprint author), 10709 Blossom Dr, Goodyear, AZ 85338 USA. EM gilvlevin@gmail.com FU National Aeronautics and Space Administration [NAS1-9690, NASW-3162, NASW-3249] FX The Viking Labeled Release results reported herein were supported by Contracts NAS1-9690, NASW-3162, and NASW-3249 from the National Aeronautics and Space Administration. NR 54 TC 0 Z9 0 U1 38 U2 38 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1531-1074 EI 1557-8070 J9 ASTROBIOLOGY JI Astrobiology PD OCT PY 2016 VL 16 IS 10 BP 798 EP 810 DI 10.1089/ast.2015.1464 PG 13 WC Astronomy & Astrophysics; Biology; Geosciences, Multidisciplinary SC Astronomy & Astrophysics; Life Sciences & Biomedicine - Other Topics; Geology GA DZ8QR UT WOS:000386136400007 PM 27626510 ER PT J AU Betsou, F Bulla, A Cho, SY Clements, J Chuaqui, R Coppola, D De Souza, Y De Wilde, A Grizzle, W Guadagni, F Gunter, E Heil, S Hodgkinson, V Kessler, J Kiehntopf, M Kim, HS Koppandi, I Shea, K Singh, R Sobel, M Somiari, S Spyropoulos, D Stone, M Tybring, G Valyi-Nagy, K Van den Eynden, G Wadhwa, L AF Betsou, Fay Bulla, Alexandre Cho, Sang Yun Clements, Judith Chuaqui, Rodrigo Coppola, Domenico De Souza, Yvonne De Wilde, Annemieke Grizzle, William Guadagni, Fiorella Gunter, Elaine Heil, Stacey Hodgkinson, Verity Kessler, Joseph Kiehntopf, Michael Kim, Hee Sung Koppandi, Iren Shea, Katheryn Singh, Rajeev Sobel, Marc Somiari, Stella Spyropoulos, Demetri Stone, Mars Tybring, Gunnel Valyi-Nagy, Klara Van den Eynden, Gert Wadhwa, Lalita TI Assays for Qualification and Quality Stratification of Clinical Biospecimens Used in Research: A Technical Report from the ISBER Biospecimen Science Working Group SO BIOPRESERVATION AND BIOBANKING LA English DT Article DE quality control; biospecimen; qualification; tissue; cells; biological fluid ID CEREBROSPINAL-FLUID; HUMAN PLASMA; SERUM-PROTEINS; CYSTATIN-C; P-SELECTIN; STORAGE; STABILITY; BIOMARKER; BLOOD; EXPRESSION AB This technical report presents quality control (QC) assays that can be performed in order to qualify clinical biospecimens that have been biobanked for use in research. Some QC assays are specific to a disease area. Some QC assays are specific to a particular downstream analytical platform. When such a qualification is not possible, QC assays are presented that can be performed to stratify clinical biospecimens according to their biomolecular quality. C1 [Betsou, Fay] Integrated BioBank Luxemburg, 6 Rue Nicolas Ernest Barble, L-1210 Luxembourg, Luxembourg. [Bulla, Alexandre] Univ Hosp Geneva, Biotheque SML, Div Genet & Lab Med DMGL, Geneva, Switzerland. [Cho, Sang Yun] Natl Biobank Korea, Cheongju, South Korea. [Clements, Judith] Queensland Univ Technol, Australian Prostate Canc Bioresource, Brisbane, Qld, Australia. [Chuaqui, Rodrigo] NCI, Canc Diag Program, Div Canc Treatment & Diag DCTD, Rockville, MD USA. [Coppola, Domenico] Univ S Florida, Moffitt Canc Ctr, Dept Anat Pathol, Tampa, FL USA. [De Souza, Yvonne] Univ Calif San Francisco, AIDS Specimen Bank, San Francisco, CA 94143 USA. [De Wilde, Annemieke] Univ Ziekenhuis Antwerpen, Edegem, Belgium. [Grizzle, William] Univ Alabama Birmingham, Birmingham, AL USA. [Guadagni, Fiorella] San Raffaele Rome Univ, IRCCS San Raffaele Pisana, Rome, Italy. [Gunter, Elaine] Specimen Solut LLC, Tucker, Rep of Georgia. [Heil, Stacey] Coriell Inst Med Res, Camden, NJ USA. [Hodgkinson, Verity] NSW Canc Council, Canc Res Div, Woolloomooloo, NSW, Australia. [Kessler, Joseph] Medpace Reference Labs, Cincinnati, OH USA. [Kiehntopf, Michael] Univ Klinikum Jena, Jena, Germany. [Kim, Hee Sung] Chung Ang Univ, Coll Med, Dept Pathol, Dongjak Gu, South Korea. [Koppandi, Iren] Cellular Technol Ltd, Shaker Hts, OH USA. [Shea, Katheryn] Precis Med Inc, Frederick, MD USA. [Singh, Rajeev] Houston Methodist Res Inst, Biorepository, Houston, TX USA. [Sobel, Marc] Amer Soc Invest Pathol, Bethesda, MD USA. [Somiari, Stella] Windber Res Inst, Biobank & Biospecimen Sci Res, Windber, PA USA. [Spyropoulos, Demetri] Med Univ South Carolina, Childrens Res Inst, Dept Pathol & Lab Med, Charleston, SC USA. [Stone, Mars] Blood Syst Res Inst, San Francisco, CA USA. [Tybring, Gunnel] Karolinska Inst, Stockholm, Sweden. [Valyi-Nagy, Klara] Univ Illinois, Coll Med, Dept Pathol, Univ Illinois Biorepository, Chicago, IL 60612 USA. [Van den Eynden, Gert] GZA Hosp, Dept Pathol & Cytol, Antwerp, Belgium. [Wadhwa, Lalita] Baylor Coll Med, Houston, TX 77030 USA. RP Betsou, F (reprint author), Integrated BioBank Luxemburg, 6 Rue Nicolas Ernest Barble, L-1210 Luxembourg, Luxembourg. EM fay.betsou@ibbl.lu OI Clements, Judith/0000-0001-6026-1964 FU NCI NIH HHS [UM1 CA183728] NR 53 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1947-5535 EI 1947-5543 J9 BIOPRESERV BIOBANK JI Biopreserv. Biobank. PD OCT PY 2016 VL 14 IS 5 BP 398 EP 409 DI 10.1089/bio.2016.0018 PG 12 WC Cell Biology; Chemistry, Applied; Medical Laboratory Technology SC Cell Biology; Chemistry; Medical Laboratory Technology GA EA3BQ UT WOS:000386473600007 PM 27046294 ER PT J AU Bledsoe, MJ Henderson, M Tasse, AM Knoppers, BM AF Bledsoe, Marianna J. Henderson, Marianne Tasse, Anne-Marie Knoppers, Bartha M. TI International Biobanking Summit V: Harmonizing Privacy Laws to Enable International Biobank Research SO BIOPRESERVATION AND BIOBANKING LA English DT Editorial Material C1 [Bledsoe, Marianna J.] ISBER Sci Policy Comm, Silver Spring, MD 20993 USA. [Henderson, Marianne] NCI, Ctr Global Hlth, Bethesda, MD 20892 USA. [Tasse, Anne-Marie] Publ Populat Project Genom & Soc P3G, Montreal, PQ, Canada. [Knoppers, Bartha M.] McGill Univ, Ctr Genom & Policy, Montreal, PQ, Canada. RP Bledsoe, MJ (reprint author), ISBER Sci Policy Comm, Silver Spring, MD 20993 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1947-5535 EI 1947-5543 J9 BIOPRESERV BIOBANK JI Biopreserv. Biobank. PD OCT PY 2016 VL 14 IS 5 BP 452 EP 453 DI 10.1089/bio.2016.29012.mjb PG 2 WC Cell Biology; Chemistry, Applied; Medical Laboratory Technology SC Cell Biology; Chemistry; Medical Laboratory Technology GA EA3BQ UT WOS:000386473600015 PM 27749136 ER PT J AU Anderson, C Milne, GL Sandler, DP Nichols, HB AF Anderson, Chelsea Milne, Ginger L. Sandler, Dale P. Nichols, Hazel B. TI Oxidative stress in relation to diet and physical activity among premenopausal women SO BRITISH JOURNAL OF NUTRITION LA English DT Article DE Oxidative stress; F-2-isoprostanes; Diet; Physical activity; Premenopausal women ID MAJOR URINARY METABOLITE; MASS-SPECTROMETRIC ASSAY; BREAST-CANCER RISK; N-3 FATTY-ACIDS; PLASMA F-2-ISOPROSTANES; CARDIOVASCULAR-DISEASE; DOCOSAHEXAENOIC ACID; ZINC SUPPLEMENTATION; ESTROGEN METABOLISM; LIPID-PEROXIDATION AB Higher levels of oxidative stress, as measured by F-2-isoprostanes, have been associated with chronic diseases such as CVD and some cancers. Improvements in diet and physical activity may help reduce oxidative stress; however, previous studies regarding associations between lifestyle factors and F-2-isoprostane concentrations have been inconsistent. The aim of this cross-sectional study was to investigate whether physical activity and intakes of fruits/vegetables, antioxidant nutrients, dietary fat subgroups and alcohol are associated with concentrations of F-2-isoprostane and the major F-2-isoprostane metabolite. Urinary F-2-isoprostane and its metabolite were measured in urine samples collected at enrolment from 912 premenopausal women (aged 35-54 years) participating in the Sister Study. Physical activity, alcohol consumption and dietary intakes were self-reported via questionnaires. With adjustment for potential confounders, the geometric means of F-2-isoprostane and its metabolite were calculated according to quartiles of dietary intakes, alcohol consumption and physical activity, and linear regression models were used to evaluate trends. Significant inverse associations were found between F-2-isoprostane and/or its metabolite and physical activity, vegetables, fruits, vitamin C, -carotene, vitamin E, -carotene, vitamin A, Se, lutein+zeaxanthin and long-chain n-3 fatty acids. Although trans fats were positively associated with both F-2-isoprostane and its metabolite, other dietary fat subgroups including SFA, n-6 fatty acids, n-3 fatty acids, MUFA, PUFA, short-chain n-3 fatty acids, long-chain n-3 fatty acids and total fat were not associated with either F-2-isoprostane or its metabolite. Our findings suggest that lower intake of antioxidant nutrients and higher intake of trans fats may be associated with greater oxidative stress among premenopausal women. C1 [Anderson, Chelsea; Nichols, Hazel B.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Milne, Ginger L.] Vanderbilt Univ, Med Ctr, Div Clin Pharmacol, Nashville, TN 37232 USA. [Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. RP Nichols, HB (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. EM hazel.nichols@unc.edu RI Milne, Ginger/D-7648-2014; OI Milne, Ginger/0000-0003-3890-151X; Sandler, Dale/0000-0002-6776-0018 FU Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences [Z01-ES044005]; Avon Foundation [02-2012-085]; National Center for Advancing Translational Sciences [KL2-TR001109] FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (Z01-ES044005), the Avon Foundation (02-2012-085) and by the National Center for Advancing Translational Sciences (KL2-TR001109). NR 63 TC 0 Z9 0 U1 2 U2 2 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0007-1145 EI 1475-2662 J9 BRIT J NUTR JI Br. J. Nutr. PD OCT PY 2016 VL 116 IS 8 BP 1416 EP 1424 DI 10.1017/S0007114516003226 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA EA8TQ UT WOS:000386912200011 PM 27725001 ER PT J AU Yang, XP Sethi, A Yanek, LR Knapper, C Nordestgaard, BG Tybjaerg-Hansen, A Becker, DM Mathias, RA Remaley, AT Becker, LC AF Yang, Xiaoping Sethi, Amar Yanek, Lisa R. Knapper, Cathy Nordestgaard, Borge G. Tybjaerg-Hansen, Anne Becker, Diane M. Mathias, Rasika A. Remaley, Alan T. Becker, Lewis C. TI SCARB1 Gene Variants Are Associated With the Phenotype of Combined High High-Density Lipoprotein Cholesterol and High Lipoprotein (a) SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE Copenhagen City Heart Study; GeneSTAR; high-density lipoprotein cholesterol; lipids and lipoproteins; lipoprotein (a); SCARB1 gene variants; SR-B1 receptor ID SCAVENGER RECEPTOR-BI; CORONARY-HEART-DISEASE; SR-BI; LDL RECEPTOR; TARGETED MUTATION; SELECTIVE UPTAKE; DEFICIENT MICE; I GENE; POPULATION; LOCUS AB Background SR-B1 (scavenger receptor class B type 1), encoded by the gene SCARB1, is a lipoprotein receptor that binds both high-density lipoprotein (HDL) and low-density lipoprotein. We reported that SR-B1 is also a receptor for lipoprotein (a) (Lp(a)), mediating cellular uptake of Lp(a) in vitro and promoting clearance of Lp(a) in vivo. Although genetic variants in SCARB1 are associated with variations in HDL level, no SCARB1 variants affecting Lp(a) have been reported. Methods and Results In an index subject with high levels of HDL cholesterol and Lp(a), SCARB1 was sequenced and demonstrated a missense mutation resulting in an S129L substitution in exon 3. To follow up, 2 cohorts (GeneSTAR, the family-based Genetic Study of Atherosclerosis Risk [n=543], and CCHS, the population-based Copenhagen City Heart Study [n=5835]) were screened for combined HDL cholesterol and Lp(a) elevations. Subjects with the extreme phenotype (HDL >80 mg/dL and Lp(a) >100 nmol/L in GeneSTAR, n=8, and >100 mg/dL in CCHS, n=9) underwent sequencing of SCARB1 exons; 15 of 18 from the combined population demonstrated genetic variants, including rare or uncommon missense or splice site mutations in 9 and homozygous synonymous variants in 6. Functional studies with 4 of the SCARB1 variants (c.386C>T, c.631-14T>G, c.4G>A, and c.631-53(m)C>T & c.726+55(m)CG>CA) showed decreased receptor function in vitro. Conclusions Human SCARB1 gene variants are associated with a new lipid phenotype, characterized by high levels of both HDL cholesterol and Lp(a). SCARB1 exonic variants often result in diminished function of translated SR-B1 via reduced binding/intracellular transport of Lp(a). C1 [Yang, Xiaoping; Yanek, Lisa R.; Becker, Diane M.; Mathias, Rasika A.; Becker, Lewis C.] Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. [Sethi, Amar; Knapper, Cathy; Remaley, Alan T.] NHLBI, Lipoprotein Metab Sect, Pulm & Vasc Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. [Nordestgaard, Borge G.; Tybjaerg-Hansen, Anne] Univ Copenhagen, Copenhagen Univ Hosp, Fac Hlth Sci, DK-1168 Copenhagen, Denmark. RP Becker, LC (reprint author), Johns Hopkins Univ Hosp, Div Cardiol, Halsted 500,600 N Wolfe St, Baltimore, MD 21287 USA. EM lbecker@jhmi.edu FU National Heart, Lung, and Blood Institute [HL72518, NR08153, HL59684, HL65608]; National Heart, Lung, and Blood Institute; National Human Genome Research Institute FX Supported by grants HL72518 (Dr L.C. Becker), NR08153 (Dr D.M. Becker), HL59684 (Dr L.C. Becker), and HL65608 (Dr L.C. Becker) from the National Heart, Lung, and Blood Institute and intramural research funding of National Heart, Lung, and Blood Institute and National Human Genome Research Institute. NR 50 TC 1 Z9 1 U1 5 U2 5 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 OCT PY 2016 VL 9 IS 5 BP 408 EP 418 DI 10.1161/CIRCGENETICS.116.001402 PG 11 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA EA4OY UT WOS:000386593700004 PM 27651445 ER PT J AU Joehanes, R Just, AC Marioni, RE Pilling, LC Reynolds, LM Mandaviya, PR Guan, WH Xu, T Elks, CE Aslibekyan, S Moreno-Macias, H Smith, JA Brody, JA Dhingra, R Yousefi, P Pankow, JS Kunze, S Shah, SH McRae, AF Lohman, K Sha, J Absher, DM Ferrucci, L Zhao, W Demerath, EW Bressler, J Grove, ML Huan, TX Liu, CY Mendelson, MM Yao, C Kiel, DP Peters, A Wang-Sattler, R Visscher, PM Wray, NR Starr, JM Ding, JZ Rodriguez, CJ Wareham, NJ Irvin, MR Zhi, DG Barrdahl, M Vineis, P Ambatipudi, S Uitterlinden, AG Hofman, A Schwartz, J Colicino, E Hou, LF Vokonas, PS Hernandez, DG Singleton, AB Bandinelli, S Turner, ST Ware, EB Smith, AK Klengel, T Binder, EB Psaty, BM Taylor, KD Gharib, SA Swenson, BR Liang, LM DeMeo, DL O'Connor, GT Herceg, Z Ressler, KJ Conneely, KN Sotoodehnia, N Kardia, SLR Melzer, D Baccarelli, AA van Meurs, JBJ Romieu, I Arnett, DK Ong, KK Liu, YM Waldenberger, M Deary, IJ Fornage, M Levy, D London, SJ AF Joehanes, Roby Just, Allan C. Marioni, Riccardo E. Pilling, Luke C. Reynolds, Lindsay M. Mandaviya, Pooja R. Guan, Weihua Xu, Tao Elks, Cathy E. Aslibekyan, Stella Moreno-Macias, Hortensia Smith, Jennifer A. Brody, Jennifer A. Dhingra, Radhika Yousefi, Paul Pankow, James S. Kunze, Sonja Shah, Sonia H. McRae, Allan F. Lohman, Kurt Sha, Jin Absher, Devin M. Ferrucci, Luigi Zhao, Wei Demerath, Ellen W. Bressler, Jan Grove, Megan L. Huan, Tianxiao Liu, Chunyu Mendelson, Michael M. Yao, Chen Kiel, Douglas P. Peters, Annette Wang-Sattler, Rui Visscher, Peter M. Wray, Naomi R. Starr, John M. Ding, Jingzhong Rodriguez, Carlos J. Wareham, Nicholas J. Irvin, Marguerite R. Zhi, Degui Barrdahl, Myrto Vineis, Paolo Ambatipudi, Srikant Uitterlinden, Andre G. Hofman, Albert Schwartz, Joel Colicino, Elena Hou, Lifang Vokonas, Pantel S. Hernandez, Dena G. Singleton, Andrew B. Bandinelli, Stefania Turner, Stephen T. Ware, Erin B. Smith, Alicia K. Klengel, Torsten Binder, Elisabeth B. Psaty, Bruce M. Taylor, Kent D. Gharib, Sina A. Swenson, Brenton R. Liang, Liming DeMeo, Dawn L. O'Connor, George T. Herceg, Zdenko Ressler, Kerry J. Conneely, Karen N. Sotoodehnia, Nona Kardia, Sharon L. R. Melzer, David Baccarelli, Andrea A. van Meurs, Joyce B. J. Romieu, Isabelle Arnett, Donna K. Ong, Ken K. Liu, Yongmei Waldenberger, Melanie Deary, Ian J. Fornage, Myriam Levy, Daniel London, Stephanie J. TI Epigenetic Signatures of Cigarette Smoking SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE biomarkers; genome-wide association study; meta-analysis; methylation; smoking ID DIFFERENTIAL DNA METHYLATION; EPIGENOME-WIDE ASSOCIATION; F2RL3 METHYLATION; HUMAN GENOME; METAANALYSIS; NUTRITION; EXPRESSION; BIOMARKERS; DISCOVERY; EXPOSURE AB Background DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers, osteoporosis, lung, and cardiovascular disorders. Methods and Results To comprehensively determine the association between cigarette smoking and DNA methylation, we conducted a meta-analysis of genome-wide DNA methylation assessed using the Illumina BeadChip 450K array on 15907 blood-derived DNA samples from participants in 16 cohorts (including 2433 current, 6518 former, and 6956 never smokers). Comparing current versus never smokers, 2623 cytosine-phosphate-guanine sites (CpGs), annotated to 1405 genes, were statistically significantly differentially methylated at Bonferroni threshold of P<1x10(-7) (18760 CpGs at false discovery rate <0.05). Genes annotated to these CpGs were enriched for associations with several smoking-related traits in genome-wide studies including pulmonary function, cancers, inflammatory diseases, and heart disease. Comparing former versus never smokers, 185 of the CpGs that differed between current and never smokers were significant P<1x10(-7) (2623 CpGs at false discovery rate <0.05), indicating a pattern of persistent altered methylation, with attenuation, after smoking cessation. Transcriptomic integration identified effects on gene expression at many differentially methylated CpGs. Conclusions Cigarette smoking has a broad impact on genome-wide methylation that, at many loci, persists many years after smoking cessation. Many of the differentially methylated genes were novel genes with respect to biological effects of smoking and might represent therapeutic targets for prevention or treatment of tobacco-related diseases. Methylation at these sites could also serve as sensitive and stable biomarkers of lifetime exposure to tobacco smoke. C1 [Joehanes, Roby; Kiel, Douglas P.] Hebrew SeniorLife, Inst Aging Res, Boston, MA USA. [Joehanes, Roby; Kiel, Douglas P.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [DeMeo, Dawn L.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Ressler, Kerry J.] Harvard Med Sch, Dept Psychiat, Boston, MA USA. [Joehanes, Roby; Huan, Tianxiao; Liu, Chunyu; Mendelson, Michael M.; Yao, Chen; Levy, Daniel] NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. [Hernandez, Dena G.; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Joehanes, Roby; Huan, Tianxiao; Liu, Chunyu; Mendelson, Michael M.; Yao, Chen; Levy, Daniel] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Just, Allan C.] Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY 10029 USA. [Marioni, Riccardo E.; Visscher, Peter M.; Starr, John M.; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland. [Marioni, Riccardo E.] Univ Edinburgh, Ctr Genom & Expt Med, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland. [Starr, John M.] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland. [Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland. [Marioni, Riccardo E.; Shah, Sonia H.; McRae, Allan F.; Visscher, Peter M.; Wray, Naomi R.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. [McRae, Allan F.; Visscher, Peter M.] Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld, Australia. [Pilling, Luke C.; Melzer, David] Univ Exeter, Sch Med, Inst Biomed & Clin Sci, Epidemiol & Publ Hlth Grp, Exeter, Devon, England. [Reynolds, Lindsay M.; Rodriguez, Carlos J.; Liu, Yongmei] Wake Forest Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC USA. [Lohman, Kurt] Wake Forest Sch Med, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC USA. [Ding, Jingzhong] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA. [Mandaviya, Pooja R.; Uitterlinden, Andre G.; van Meurs, Joyce B. J.] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands. [Mandaviya, Pooja R.] Erasmus Univ, Med Ctr, Dept Clin Chem, Rotterdam, Netherlands. [Hofman, Albert] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Guan, Weihua] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN USA. [Pankow, James S.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Xu, Tao; Kunze, Sonja; Peters, Annette; Wang-Sattler, Rui; Waldenberger, Melanie] Helmhotz Zentrum Muenchen, Inst Epidemiol 2, Res Unit Mol Epidemiol, Munich, Germany. [Elks, Cathy E.; Wareham, Nicholas J.; Ong, Ken K.] Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England. [Aslibekyan, Stella; Sha, Jin; Irvin, Marguerite R.; Arnett, Donna K.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA. [Moreno-Macias, Hortensia] Autonomous Metropolitan Univ Iztapalapa, Mexico City, DF, Mexico. [Moreno-Macias, Hortensia; Ambatipudi, Srikant; Herceg, Zdenko; Romieu, Isabelle] Int Agcy Res Canc, Lyon, France. [Smith, Jennifer A.; Zhao, Wei; Ware, Erin B.; Kardia, Sharon L. R.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Ware, Erin B.] Univ Michigan, Inst Social Res, Res Ctr Grp Dynam, Ann Arbor, MI USA. [Brody, Jennifer A.; Psaty, Bruce M.; Swenson, Brenton R.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Gharib, Sina A.] Univ Washington, Dept Med, Ctr Lung Biol, Div Pulm & Crit Care Med, Seattle, WA USA. [Sotoodehnia, Nona] Univ Washington, Dept Epidemiol, Div Cardiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Dhingra, Radhika] Emory Univ, Rollins Sch Publ Hlth, Dept Environm Hlth, Atlanta, GA 30322 USA. [Yousefi, Paul; Demerath, Ellen W.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Absher, Devin M.] HudsonAlpha Inst Biotechnol, Huntsville, AL USA. [Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Bressler, Jan; Grove, Megan L.; Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA. [Zhi, Degui] Univ Texas Hlth Sci Ctr Houston, Sch Biomed Informat, Houston, TX 77030 USA. [Mendelson, Michael M.] Boston Childrens Hosp, Dept Cardiol, Boston, MA USA. [Barrdahl, Myrto] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Vineis, Paolo] Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London, England. [Vineis, Paolo] HuGeF Fdn, Turin, Italy. [Sha, Jin; Baccarelli, Andrea A.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Baccarelli, Andrea A.] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Hou, Lifang] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Hou, Lifang] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Vokonas, Pantel S.] VA Boston Healthcare Syst, VA Normat Aging Study, Boston, MA USA. [Vokonas, Pantel S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy. [Turner, Stephen T.] Mayo Clin, Div Nephrol & Hypertens, Rochester, MN USA. [Smith, Alicia K.; Binder, Elisabeth B.; Ressler, Kerry J.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. [Conneely, Karen N.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA. [Klengel, Torsten; Binder, Elisabeth B.] Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany. [Klengel, Torsten; Ressler, Kerry J.] McLean Hosp, Div Depress & Anxiety Disorders, 115 Mill St, Belmont, MA 02178 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Taylor, Kent D.] Los Angeles BioMed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA USA. [Taylor, Kent D.] Harbor UCLA Med Ctr, Div Genom Outcomes, Dept Pediat, Torrance, CA 90509 USA. [Taylor, Kent D.] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. [Taylor, Kent D.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Taylor, Kent D.] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA. [Liang, Liming] Harvard Sch Publ Hlth, Boston, MA USA. [O'Connor, George T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [London, Stephanie J.] NIEHS, Epidemiol Branch, US Dept HHS, NIH, POB 12233,Room A306, Res Triangle Pk, NC 27709 USA. RP London, SJ (reprint author), NIEHS, Epidemiol Branch, US Dept HHS, NIH, POB 12233,Room A306, Res Triangle Pk, NC 27709 USA. EM london2@niehs.nih.gov RI Shah, Sonia/N-7547-2013; OI Mendelson, Michael/0000-0001-7590-3958; Shah, Sonia/0000-0001-5860-4526; London, Stephanie/0000-0003-4911-5290; Colicino, Elena/0000-0002-1875-8448; Smith, Jennifer/0000-0002-3575-5468; Just, Allan/0000-0003-4312-5957; Pankow, James/0000-0001-7076-483X; AMBATIPUDI, SRIKANT/0000-0003-3102-3603 FU National Heart, Lung, and Blood Institute [R01HL105756]; NIH; National Institute of Environmental Health Sciences; National Heart Lung and Blood Institute FX Infrastructure for the CHARGE consortium is provided by the National Heart, Lung, and Blood Institute grant R01HL105756. This work was supported in part by the Intramural Research Program of the NIH; National Institute of Environmental Health Sciences; and the National Heart Lung and Blood Institute. Additional funding sources for each cohort can be found in the Data Supplement. NR 43 TC 6 Z9 6 U1 9 U2 9 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 OCT PY 2016 VL 9 IS 5 BP 436 EP 447 DI 10.1161/CIRCGENETICS.116.001506 PG 12 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA EA4OY UT WOS:000386593700007 PM 27651444 ER PT J AU Mital, S Musunuru, K Garg, V Russell, MW Lanfear, DE Gupta, RM Hickey, KT Ackerman, MJ Perez, MV Roden, DM Woo, D Fox, CS Ware, S AF Mital, Seema Musunuru, Kiran Garg, Vidu Russell, Mark W. Lanfear, David E. Gupta, Rajat M. Hickey, Kathleen T. Ackerman, Michael J. Perez, Marco V. Roden, Dan M. Woo, Daniel Fox, Caroline S. Ware, Stephanie TI Enhancing Literacy in Cardiovascular Genetics: A Scientific Statement From the American Heart Association SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE AHA Scientific Statements; aneurysm; arrhythmia; cardiomyopathy; channelopathy; congenital heart defects; genetic testing; genetics; pharmacogenetics; pharmacology ID LONG QT SYNDROME; OF-FUNCTION POLYMORPHISM; PRIMARY-CARE; MEDICAL GENETICS; DILATED CARDIOMYOPATHY; MUSCULAR-DYSTROPHIES; CLINICAL MANAGEMENT; CONSENSUS STATEMENT; PRACTICE GUIDELINES; INCIDENTAL FINDINGS AB Advances in genomics are enhancing our understanding of the genetic basis of cardiovascular diseases, both congenital and acquired, and stroke. These advances include finding genes that cause or increase the risk for childhood and adult-onset diseases, finding genes that influence how patients respond to medications, and the development of genetics-guided therapies for diseases. However, the ability of cardiovascular and stroke clinicians to fully understand and apply this knowledge to the care of their patients has lagged. This statement addresses what the specialist caring for patients with cardiovascular diseases and stroke should know about genetics; how they can gain this knowledge; how they can keep up-to-date with advances in genetics, genomics, and pharmacogenetics; and how they can apply this knowledge to improve the care of patients and families with cardiovascular diseases and stroke. C1 [Mital, Seema] Hosp Sick Children, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. [Musunuru, Kiran] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Ackerman, Michael J.] Mayo Clin, Rochester, MN USA. [Fox, Caroline S.] NHLBI, Bldg 10, Bethesda, MD 20892 USA. [Garg, Vidu] Ohio State Univ, Nationwide Childrens Hosp, Columbus, OH 43210 USA. [Gupta, Rajat M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hickey, Kathleen T.] Columbia Univ, Med Ctr, New York, NY 10027 USA. [Lanfear, David E.] Henry Ford Hosp, Detroit, MI 48202 USA. [Perez, Marco V.] Stanford Univ, Stanford, CA 94305 USA. [Roden, Dan M.] Vanderbilt Univ, Sch Med, 221 Kirkland Hall, Nashville, TN 37235 USA. [Russell, Mark W.] Univ Michigan, Ann Arbor, MI 48109 USA. [Ware, Stephanie] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Woo, Daniel] Univ Cincinnati, Cincinnati, OH 45221 USA. RP Mital, S (reprint author), Hosp Sick Children, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. RI Garg, Vidu/D-8240-2012 OI Garg, Vidu/0000-0002-3778-5927 FU NIH; Janssen; Portola; HeartWare; BioControl; Amgen; AHA; Burroughs Wellcome; March of Dimes FX David E. Lanfear Henry Ford Hospital NIH dagger; Janssen dagger; Portolastar; HeartWare dagger; BioControlstar; Amgen dagger; Stephanie Ware Indiana University School of Medicine AHA dagger; Burroughs Wellcome dagger; March of Dimes dagger; NIH dagger NR 126 TC 2 Z9 2 U1 4 U2 4 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 OCT PY 2016 VL 9 IS 5 BP 448 EP 467 DI 10.1161/HCG.0000000000000031 PG 20 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA EA4OY UT WOS:000386593700008 PM 27672144 ER PT J AU Kendall, BJ Rubenstein, JH Cook, MB Vaughan, TL Anderson, LA Murray, LJ Shaheen, NJ Corley, DA Chandar, AK Li, L Greer, KB Chak, A El-Serag, HB Whiteman, DC Thrift, AP AF Kendall, Bradley J. Rubenstein, Joel H. Cook, Michael B. Vaughan, Thomas L. Anderson, Lesley A. Murray, Liam J. Shaheen, Nicholas J. Corley, Douglas A. Chandar, Apoorva K. Li, Li Greer, Katarina B. Chak, Amitabh El-Serag, Hashem B. Whiteman, David C. Thrift, Aaron P. TI Inverse Association Between Gluteofemoral Obesity and Risk of Barrett's Esophagus in a Pooled Analysis SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE BEACON; Obesity; Esophageal Cancer; Epidemiology; Risk Factors ID BODY-MASS INDEX; ABDOMINAL OBESITY; GASTROESOPHAGEAL-REFLUX; CENTRAL ADIPOSITY; ADENOCARCINOMA; DISEASE; CANCER; SEX; METAANALYSIS; INSULIN AB BACKGROUND & AIMS: Gluteofemoral obesity (determined by measurement of subcutaneous fat in the hip and thigh regions) could reduce risks of cardiovascular and diabetic disorders associated with abdominal obesity. We evaluated whether gluteofemoral obesity also reduces the risk of Barrett's esophagus (BE), a premalignant lesion associated with abdominal obesity. METHODS: We collected data from non-Hispanic white participants in 8 studies in the Barrett's and Esophageal Adenocarcinoma Consortium. We compared measures of hip circumference (as a proxy for gluteofemoral obesity) from cases of BE (n = 1559) separately with 2 control groups: 2557 population-based controls and 2064 individuals with gastroesophageal reflux disease (GERD controls). Study-specific odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using individual participant data and multivariable logistic regression and combined using a random-effects meta-analysis. RESULTS: We found an inverse relationship between hip circumference and BE (OR per 5-cmincrease, 0.88; 95% CI, 0.81-0.96), compared with population-based controls in a multivariable model that included waist circumference. This association was not observed in models that did not include waist circumference. Similar results were observed in analyses stratified by frequency of GERD symptoms. The inverse association with hip circumference was statistically significant only among men (vs population-based controls: OR, 0.85; 95% CI, 0.76-0.96 for men; OR, 0.93; 95% CI, 0.74-1.16 for women). For men, within each category of waist circumference, a larger hip circumference was associated with a decreased risk of BE. Increasing waist circumference was associated with an increased risk of BE in the mutually adjusted population-based and GERD control models. CONCLUSIONS: Although abdominal obesity is associated with an increased risk of BE, there is an inverse association between gluteofemoral obesity and BE, particularly among men. C1 [Kendall, Bradley J.; Whiteman, David C.] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia. [Kendall, Bradley J.] Univ Queensland, Sch Med, Brisbane, Qld, Australia. [Rubenstein, Joel H.] Ann Arbor Vet Affairs Med Ctr, Ctr Clin Management Res, Ann Arbor, MI USA. [Rubenstein, Joel H.] Univ Michigan, Sch Med, Dept Internal Med, Barretts Esophagus Program,Div Gastroenterol, Ann Arbor, MI USA. [Cook, Michael B.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Vaughan, Thomas L.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. [Anderson, Lesley A.; Murray, Liam J.] Queens Univ Belfast, Ctr Publ Hlth, Belfast, Antrim, North Ireland. [Shaheen, Nicholas J.] Univ N Carolina, Sch Med, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. [Corley, Douglas A.] Kaiser Permanente, Div Res, Oakland, CA USA. [Corley, Douglas A.] San Francisco Med Ctr, San Francisco, CA USA. [Chandar, Apoorva K.; Greer, Katarina B.; Chak, Amitabh] Case Western Reserve Univ, Div Gastroenterol & Liver Dis, Cleveland, OH 44106 USA. [Li, Li] Case Western Reserve Univ, Swetland Ctr Environm Hlth, Dept Family Med, Cleveland, OH 44106 USA. [El-Serag, Hashem B.] Michael E DeBakey VA Med Ctr, Ctr Innovat Qual Effectiveness & Safety, Houston VA Hlth Serv Res & Dev, Dept Med, Houston, TX USA. [Whiteman, David C.; Thrift, Aaron P.] Baylor Coll Med, Dept Med, Sect Gastroenterol & Hepatol, Houston, TX 77030 USA. [Thrift, Aaron P.] Baylor Coll Med, Dan L Duncan Comprehens Canc Ctr, One Baylor Plaza,MS BCM305, Houston, TX 77030 USA. RP Thrift, AP (reprint author), Baylor Coll Med, Dept Med, Sect Gastroenterol & Hepatol, Houston, TX 77030 USA.; Thrift, AP (reprint author), Baylor Coll Med, Dan L Duncan Comprehens Canc Ctr, One Baylor Plaza,MS BCM305, Houston, TX 77030 USA. EM aaron.thrift@bcm.edu OI Anderson, Lesley/0000-0002-1000-3649; Whiteman, David/0000-0003-2563-9559 FU National Institutes of Health [RO1 DK63616, 1R21DK077742, K23DK59311, R03 DK75842, K23DK079291, R01 CA116845, K24-04-107]; NCI [U54CA163060]; Intramural Program of the National Institutes of Health; Ireland-Northern Ireland cooperation research project grant - Northern Ireland Research and Development Office; Health Research Board, Ireland [RES/1699/01N/S]; Study of Digestive Health grant [NCI RO1 CA 001833]; Study of Reflux Disease grant [NCI R01 CA72866]; Established Investigator Award in Cancer Prevention and Control grant [K05 CA124911]; US Department of Veterans Affairs [I01-CX000899]; US Public Health Service [R21 CA135692] FX This work was supported by the National Institutes of Health RO1 DK63616 (D.A.C.), 1R21DK077742 (N.J.S. and D.A.C.), K23DK59311 (N.J.S.), R03 DK75842 (N.J.S.), K23DK079291 (J.H.R.), R01 CA116845 (H.B.E.-S.), K24-04-107 (H.B.E.-S.); NCI grant U54CA163060 (A.C.); the Intramural Program of the National Institutes of Health (M.B.C.); an Ireland-Northern Ireland cooperation research project grant sponsored by the Northern Ireland Research and Development Office and the Health Research Board, Ireland (Factors Influencing the Barrett's/Adenocarcinoma Relationship) (RES/1699/01N/S to L.J.M.); the Study of Digestive Health grant NCI RO1 CA 001833 (D.C.W.); the Study of Reflux Disease grant NCI R01 CA72866 (T.L.V.); the Established Investigator Award in Cancer Prevention and Control grant K05 CA124911 (T.L.V.); the US Department of Veterans Affairs grant CSRD Merit I01-CX000899 (J.H.R.); and US Public Health Service research grant R21 CA135692 (A.C.). NR 37 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 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD OCT PY 2016 VL 14 IS 10 BP 1412 EP + DI 10.1016/j.cgh.2016.05.032 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA EA6SO UT WOS:000386759500011 PM 27264393 ER PT J AU Papadakis, GZ Millo, C Stratakis, CA AF Papadakis, Georgios Z. Millo, Corina Stratakis, Constantine A. TI Benign hormone-secreting adenoma within a larger adrenocortical mass showing intensely increased activity on F-18-FDG PET/CT SO ENDOCRINE LA English DT Article DE F-18-FDG PET/CT; Computed Tomography (CT); Adrenal glands; Adenoma(s) ID LESIONS AB Adrenal adenomas usually show F-18-FDG activity less than that of the liver parenchyma. However, lipid-poor and hormone-secreting adenomas have been reported to show mild F-18-FDG avidity. We report on a 51-year-old female with clinical symptoms of hypercortisolemia and a large right adrenal mass detected on CT. Post-contrast CT images showed an enhancing focus in the lower pole of the mass, with corresponding markedly increased activity on F-18-FDG PET/CT. Right adrenalectomy was performed and histology revealed a benign adenoma, indicating that functioning benign adenomas can show intensely increased metabolic activity on F-18-FDG mimicking malignancy. C1 [Papadakis, Georgios Z.] NIH, Radiol & Imaging Sci, Warren Grant Magnuson Clin Ctr CC, Bldg 10, Bethesda, MD 20892 USA. [Millo, Corina] RAD&IS, Div Nucl Med, Bethesda, MD 20892 USA. [Millo, Corina] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, CRC, Bldg 10,Room 1-3330,MSC1103, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, CRC, Bldg 10,Room 1-3330,MSC1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov FU Intramural NIH HHS [ZIA HD008920-04] NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-008X EI 1559-0100 J9 ENDOCRINE JI Endocrine PD OCT PY 2016 VL 54 IS 1 BP 269 EP 270 DI 10.1007/s12020-016-0969-7 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EA4WL UT WOS:000386616300031 PM 27154873 ER PT J AU Chang, FE Beall, SA Cox, JM Richter, KS DeCherney, AH Levy, MJ AF Chang, Frank E. Beall, Stephanie A. Cox, Jeris M. Richter, Kevin S. DeCherney, Alan H. Levy, Michael J. TI Assessing the adequacy of gonadotropin-releasing hormone agonist leuprolide to trigger oocyte maturation and management of inadequate response SO FERTILITY AND STERILITY LA English DT Article DE Gonadotropin-releasing hormone (GnRH) agonist; leuprolide acetate; human chorionic gonadotropin (hCG); retrigger; in vitro fertilization (IVF) ID OVARIAN HYPERSTIMULATION SYNDROME; IN-VITRO FERTILIZATION; HIGH-RISK PATIENTS; GNRH AGONIST; PREGNANCY RATES; LUTEAL SUPPORT; HCG; ANTAGONIST; MULTICENTER; COTREATMENT AB Objective: To compare outcomes of in vitro fertilization (IVF) cycles with adequate versus inadequate response to the gonadotropin-releasing hormone (GnRH) agonist trigger rescued with the use of human chorionic gonadotropin (hCG) retrigger, and to identify risk factors associated with an inadequate trigger. Design: Retrospective cohort study. Setting: Private practice. Patient(s): Women at high risk for ovarian hyperstimulation syndrome who underwent an autologous IVF cycle and used GnRH agonist to trigger oocyte maturation before oocyte retrieval. Intervention(s): Patients were triggered with GnRH agonist for final oocyte maturation before retrieval. Patients with an inadequate response, defined by low post-trigger serum LH and P concentrations or failure to recover oocytes after aspiration of several follicles, were retriggered with hCG. Main Outcome Measure(s): Number of oocytes retrieved, fertilization rate, clinical pregnancy, and live birth. Result(s): Two percent of patients triggered with GnRH agonist had an inadequate response and were retriggered with hCG. There was no statistically significant difference in clinical outcomes between the cycles that were retriggered with hCG and successful GnRH agonist triggers. Low body mass index, low baseline LH, and higher total dosage of gonadotropins required for stimulation were associated with an increased risk of having an inadequate response to the GnRH agonist trigger. Conclusion(s): A small minority of patients triggered with GnRH agonist had an inadequate response. Rescheduling of oocyte retrieval after hCG retrigger yielded similar IVF outcomes. Evaluation of trigger response based on serum LH and P concentrations is time dependent. Patient characteristics suggestive of hypothalamic hypofunction were predictive of an inadequate response to the GnRH agonist trigger. (C) 2016 by American Society for Reproductive Medicine. C1 [Chang, Frank E.; Beall, Stephanie A.; Richter, Kevin S.; Levy, Michael J.] Shady Grove Fertil Reprod Sci Ctr, 15001 Shady Grove Rd, Rockville, MD 20850 USA. [Beall, Stephanie A.; Cox, Jeris M.; DeCherney, Alan H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. RP Chang, FE (reprint author), Shady Grove Fertil Reprod Sci Ctr, 15001 Shady Grove Rd, Rockville, MD 20850 USA. EM frank.chang@integramed.com NR 21 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2016 VL 106 IS 5 BP 1093 EP + DI 10.1016/j.fertnstert.2016.06.013 PG 11 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA EA7RG UT WOS:000386828800022 PM 27341988 ER PT J AU Owen, CM Pal, L Mumford, SL Freeman, R Isaac, B McDonald, L Santoro, N Taylor, HS Wolff, EF AF Owen, Carter M. Pal, Lubna Mumford, Sunni L. Freeman, Ruth Isaac, Barbara McDonald, Linda Santoro, Nanette Taylor, Hugh S. Wolff, Erin F. TI Effects of hormones on skin wrinkles and rigidity vary by race/ethnicity: four-year follow-up from the ancillary skin study of the Kronos Early Estrogen Prevention Study SO FERTILITY AND STERILITY LA English DT Article DE Menopause; hormone therapy; skin wrinkles; skin rigidity; race ID POSTMENOPAUSAL WOMEN; ETHNIC-DIFFERENCES; COLLAGEN CONTENT; THERAPY; ESTRADIOL AB Objective: To measure skin wrinkles and rigidity in menopausal women of varying race/ethnicity with or without hormone therapy (HT) for up to four years. Design: Randomized, double-blind, placebo-controlled trial. Setting: Academic medical centers. Patient(s): Women (42-58 years of age) within 36 months of last menstrual period and enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). Intervention(s): Treatment with 0.45 mg oral conjugated equine estrogens (CEE), transdermal E-2 (50 mu g/d) with micronized P (200 mg daily), or placebo for 4 years. Main Outcome Measure(s): Skin wrinkles were assessed at 11 locations on the face and neck, and skin rigidity was assessed at the forehead and cheek at baseline and yearly for 4 years. Result(s): Neither total wrinkle score nor total rigidity score was significantly different at baseline or over the 4-year follow-up among patients randomized to CEE, E-2, or placebo. Skin wrinkle and rigidity scores were primarily affected by race/ethnicity, with scores being significantly different between races for almost all of the wrinkle parameters and for all of the rigidity measures. There was no association between race and response to HT for total wrinkle or rigidity scores. Black women had the lowest wrinkle scores compared with white women across all 4 years. In general, skin rigidity decreased in all groups over time, but black women had significantly reduced total facial rigidity compared with white women after 4 years. Conclusion(s): Race is the strongest predictor of the advancement of skin aging in the 4 years following menopause. HT does not appear to affect skin wrinkles or rigidity at most facial locations. Clinical Trial Registration Number: NCT00154180. (Fertil Steril (R) 2016;106:1170-5. (C) 2016 by American Society for Reproductive Medicine.) C1 [Owen, Carter M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. [Pal, Lubna; McDonald, Linda; Taylor, Hugh S.] Yale Univ, Dept Obstet Gynecol & Reprod Sci, New Haven, CT USA. [Mumford, Sunni L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Bethesda, MD USA. [Freeman, Ruth; Isaac, Barbara] Albert Einstein Coll Med, Obstet & Gynecol & Womens Hlth, Div Reprod Endocrinol & Infertil, Bronx, NY 10467 USA. [Santoro, Nanette] Univ Colorado, Dept Obstet & Gynecol & Womens Hlth, Denver Sch Med, Aurora, CO USA. [Wolff, Erin F.] Celmatix, New York, NY USA. RP Owen, CM (reprint author), Program Reprod & Adult Endocrinol, 10 CRC,Room 1E-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM carter.owen@mail.nih.gov FU Bayer Women's Healthcare; Pfizer; Bayer; Abbvie; Euroscreen; Kronos Longevity Research Institute Reproductive Scientist Development Program [NIH K12HD00849]; Berlex Foundation; National Institutes of Health [U54 HD052668]; Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland FX C.M.O. has nothing to disclose. L.P. has nothing to disclose. S.L.M. has nothing to disclose. R.F. has nothing to disclose. B.I. has nothing to disclose. L.M. has nothing to disclose. N.S. reports stock options in Menogenix and investigator-initiated grant support from Bayer Women's Healthcare. H.S.T. reports grants and personal fees from Pfizer, Bayer, and Abbvie and personal fees from Euroscreen. E.F.W. has nothing to disclose.; Supported by the Kronos Longevity Research Institute Reproductive Scientist Development Program (NIH K12HD00849) and the Berlex Foundation (E.F.W.), the National Institutes of Health (U54 HD052668, H.S.T.), and the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland. NR 17 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2016 VL 106 IS 5 BP 1170 EP + DI 10.1016/j.fertnstert.2016.06.023 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA EA7RG UT WOS:000386828800033 PM 27393520 ER PT J AU Rupert, CB Heltzel, JMH Taylor, DJ Rusche, LN AF Rupert, Christopher B. Heltzel, Justin M. H. Taylor, Derek J. Rusche, Laura N. TI Sporadic Gene Loss After Duplication Is Associated with Functional Divergence of Sirtuin Deacetylases Among Candida Yeast Species SO G3-GENES GENOMES GENETICS LA English DT Article DE Sir2; Hst1; specifically retained ancestral gene; CTG clade ID SACCHAROMYCES-CEREVISIAE; PHYLOGENETIC ANALYSIS; ALBICANS; EXPRESSION; SIR2; DNA; HETEROCHROMATIN; BIODIVERSITY; SELECTION; GENOMICS AB Gene duplication promotes the diversification of protein functions in several ways. Ancestral functions can be partitioned between the paralogs, or a new function can arise in one paralog. These processes are generally viewed as unidirectional. However, paralogous proteins often retain related functions and can substitute for one another. Moreover, in the event of gene loss, the remaining paralog might regain ancestral functions that had been shed. To explore this possibility, we focused on the sirtuin deacetylase SIR2 and its homolog HST1 in the CTG clade of yeasts. HST1 has been consistently retained throughout the clade, whereas SIR2 is only present in a subset of species. These NAD(+)-dependent deacetylases generate condensed chromatin that represses transcription and stabilizes tandemly repeated sequences. By analyzing phylogenetic trees and gene order, we found that a single duplication of the SIR2/HST1 gene occurred, likely prior to the emergence of the CTG clade. This ancient duplication was followed by at least two independent losses of SIR2. Functional characterization of Sir2 and Hst1 in three species revealed that these proteins have not maintained consistent functions since the duplication. In particular, the rDNA locus is deacetylated by Sir2 in Candida albicans, by Hst1 in C. lusitaniae, and by neither paralog in C. parapsilosis. In addition, the subtelomeres in C. albicans are deacetylated by Sir2 rather than by Hst1, which is orthologous to the sirtuin associated with Saccharomyces cerevisiae subtelomeres. These differences in function support the model that sirtuin deacetylases can regain ancestral functions to compensate for gene loss. C1 [Rupert, Christopher B.; Heltzel, Justin M. H.; Taylor, Derek J.; Rusche, Laura N.] SUNY Buffalo, Dept Biol Sci, 109 Cooke Hall, Buffalo, NY 14260 USA. [Heltzel, Justin M. H.] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA. RP Rusche, LN (reprint author), SUNY Buffalo, Dept Biol Sci, 109 Cooke Hall, Buffalo, NY 14260 USA. EM lrusche@buffalo.edu FU National Science Foundation [MCB-1121569, ARC-1023334] FX We thank G. Butler and S. Noble for strains and plasmids, and the members of the Rusche lab for helpful discussion. This research was supported by grants from the National Science Foundation to L.N.R. (MCB-1121569) and D.J.T. (ARC-1023334). NR 48 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2016 VL 6 IS 10 BP 3297 EP 3305 DI 10.1534/g3.116.033845 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA EA4KM UT WOS:000386581200023 PM 27543294 ER PT J AU Bolte, FJ O'Keefe, A Serti, E Rivera, E Liang, TJ Ghany, MG Rehermann, B AF Bolte, Fabian J. O'Keefe, Ashley Serti, Elisavet Rivera, Elenita Liang, T. Jake Ghany, Marc G. Rehermann, Barbara TI Monocyte-dependent activation of intrahepatic mucosal associated invariant T cells resolves within weeks of antiviral therapy for hepatitis C SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Bolte, Fabian J.; O'Keefe, Ashley; Serti, Elisavet; Rivera, Elenita; Liang, T. Jake; Ghany, Marc G.; Rehermann, Barbara] NIDDK, Liver Dis Branch, NIH, DHHS, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 10 BP 5A EP 5A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493800011 ER PT J AU Uchida, T Walsh, K Hiraga, N Imamura, M Koh, C Glenn, J Uprichard, SL Heller, T Dahari, H Chayama, K AF Uchida, Takuro Walsh, Kevin Hiraga, Nobuhiko Imamura, Michio Koh, Christopher Glenn, Jeffrey Uprichard, Susan L. Heller, Theo Dahari, Harel Chayama, Kazuaki TI Characterization of HDV and HBV kinetics during acute co-infection and interferon-alpha treatment in uPA/SCID chimeric mice with humanized livers SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Walsh, Kevin; Uprichard, Susan L.; Dahari, Harel] Loyola Univ, Med Ctr, Program Expt & Theoret Modeling, Div Hepatol,Dept Med, 2160 S 1st Ave, Maywood, IL 60153 USA. [Uchida, Takuro; Hiraga, Nobuhiko; Imamura, Michio; Chayama, Kazuaki] Hiroshima Univ, Inst Biomed & Hlth Sci, Dept Gastroenterol & Metab, Appl Life Sci, Hiroshima, Japan. [Koh, Christopher; Heller, Theo] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Glenn, Jeffrey] Stanford Univ, Sch Med, Div Gastroenterol & Hepatol, Stanford, CA USA. [Uprichard, Susan L.] Loyola Univ, Med Ctr, Dept Microbiol & Immunol, 2160 S 1st Ave, Maywood, IL 60153 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 18 BP 9A EP 10A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493800019 ER PT J AU Emmanuel, B Gross, C Masur, H Kottilil, S Kattakuzhy, S AF Emmanuel, Benjamin Gross, Chloe Masur, Henry Kottilil, Shyam Kattakuzhy, Sarah TI High Efficacy in Real-World Treatment of Cirrhotic Patients by Non-Specialist Providers SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Emmanuel, Benjamin; Gross, Chloe; Kottilil, Shyam; Kattakuzhy, Sarah] Univ Maryland, Sch Med, Inst Human Virol, Div Clin Care & Res, Baltimore, MD 21201 USA. [Masur, Henry] NIH, Crit Care, Bldg 10, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 22 BP 11A EP 12A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493800023 ER PT J AU Ajmera, VH Belt, PH Wilson, L Gill, RM Loomba, R Kleiner, DE Tetri, BA Terrault, N AF Ajmera, Veeral H. Belt, Patricia H. Wilson, Laura Gill, Ryan M. Loomba, Rohit Kleiner, David E. Tetri, Brent A. Terrault, Norah TI No Benefit from Modest Alcohol Use in Nonalcoholic Fatty Liver Disease (NAFLD) SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Ajmera, Veeral H.; Terrault, Norah] UCSF, Gastroenterol, San Francisco, CA USA. [Belt, Patricia H.; Wilson, Laura] Johns Hopkins Univ, Baltimore, MD USA. [Gill, Ryan M.] UCSF, Pathol, San Francisco, CA USA. [Loomba, Rohit] Univ Calif San Diego, San Diego, CA USA. [Kleiner, David E.] NCI, Pathol, Bethesda, MD 20892 USA. [Tetri, Brent A.] St Luis Univ, St Louis, MO 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 31 BP 16A EP 16A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493800032 ER PT J AU Kleiner, DE Brunt, EM Belt, PH Wilson, L Guy, CD Yeh, MM Gill, RM Kowdley, KV Tetri, BA Sanyal, AJ AF Kleiner, David E. Brunt, Elizabeth M. Belt, Patricia H. Wilson, Laura Guy, Cynthia D. Yeh, Matthew M. Gill, Ryan M. Kowdley, Kris V. Tetri, Brent A. Sanyal, Arun J. TI Diagnostic Pattern and Disease Activity Are Related To Disease Progression and Regression in Nonalcoholic Fatty Liver Disease SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Sanyal, Arun J.] Virginia Commonwealth Univ, Richmond, VA USA. [Kleiner, David E.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Brunt, Elizabeth M.] Washington Univ, St Louis, MO USA. [Belt, Patricia H.; Wilson, Laura] Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. [Guy, Cynthia D.] Duke Univ, Durham, NC USA. [Yeh, Matthew M.] Univ Washington, Seattle, WA USA. [Gill, Ryan M.] Univ Calif San Francisco, San Francisco, CA USA. [Kowdley, Kris V.] Swedish Med Ctr, Seattle, WA USA. [Tetri, Brent A.] St Louis Univ, St Louis, MO 63103 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 BP 19A EP 19A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493800038 ER PT J AU Puri, P Mirshahi, F Daita, K Vincent, R Liangpunsakul, S Chalasani, NP Crabb, DW Shah, V Kamath, PS Gores, GJ Katz, BP Radaeva, S Sanyal, AJ AF Puri, Puneet Mirshahi, Faridoddin Daita, Kalyani Vincent, Robert Liangpunsakul, Suthat Chalasani, Naga P. Crabb, David W. Shah, Vijay Kamath, Patrick S. Gores, Gregory J. Katz, Barry P. Radaeva, Svetlana Sanyal, Arun J. TI Quantitative and Qualitative Changes in the Circulating Microbiome Are Associated With the Development and Severity of Alcoholic Hepatitis SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Puri, Puneet; Mirshahi, Faridoddin; Daita, Kalyani; Vincent, Robert; Sanyal, Arun J.] Virginia Commonwealth Univ, Richmond, VA USA. [Liangpunsakul, Suthat; Chalasani, Naga P.; Crabb, David W.; Katz, Barry P.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Shah, Vijay; Kamath, Patrick S.; Gores, Gregory J.] Mayo Clin, Rochester, MN USA. [Radaeva, Svetlana] NIAAA, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 48 BP 25A EP 25A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493800049 ER PT J AU Alao, H Cam, M Zhang, F Suarez, DF Henderson, WA Fourie, NI Li, QS Liang, TJ Ghany, MG AF Alao, Hawwa Cam, Margaret Zhang, Fang Suarez, Daniel F. Henderson, Wendy A. Fourie, N. I. Li, Qisheng Liang, T. Jake Ghany, Marc G. TI Role Of MiRNAs In Hepatitis C Virus Clearance In Prior Non-Responders During Therapy With DAAs SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Alao, Hawwa; Zhang, Fang; Suarez, Daniel F.; Li, Qisheng; Liang, T. Jake; Ghany, Marc G.] NIDDK, NIH, Baltimore, MD USA. [Cam, Margaret] NCI, NIH, Bethesda, MD 20892 USA. [Henderson, Wendy A.; Fourie, N. I.] NINR, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 66 BP 34A EP 35A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493800067 ER PT J AU Asselah, T Shiha, G Feld, JJ Abergel, A Kohli, A Kottilil, S Ruane, PJ Naggie, S Letterio, C Hahambis, TA Llewellyn, J Natha, M Kersey, K McNally, J Brainard, DM Esmat, GE AF Asselah, Tarik Shiha, Gamal Feld, Jordan J. Abergel, Armando Kohli, Anita Kottilil, Shyam Ruane, Peter J. Naggie, Susanna Letterio, Cathleen Hahambis, Thomas A. Llewellyn, Joseph Natha, Macky Kersey, Kathryn McNally, John Brainard, Diana M. Esmat, Gamal E. TI Integrated Analysis of SOF plus RBV, LDV/SOF or SOF/VEL for the Treatment of Genotype 4 Chronic HCV Infection SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Letterio, Cathleen; Hahambis, Thomas A.; Llewellyn, Joseph; Natha, Macky; Kersey, Kathryn; McNally, John; Brainard, Diana M.] Gilead Sci, Foster City, CA USA. [Kohli, Anita] Creighton Univ, Sch Med, Phoenix, AZ USA. [Feld, Jordan J.] Toronto Western Hosp, Toronto, ON, Canada. [Ruane, Peter J.] Ruane Med & Liver Hlth Inst, Los Angeles, CA USA. [Shiha, Gamal] Almansoura Univ Hosp, Mansoura, Egypt. [Abergel, Armando] Beaujon Hosp, Clermont Ferrand, France. [Asselah, Tarik] Hop Beaujon, Serv Hepatol, Clichy, France. [Asselah, Tarik] Hop Beaujon, INSERM, U773, CRB3, Clichy, France. [Naggie, Susanna] Duke Clin Res Inst, Durham, NC USA. [Kottilil, Shyam] NIAID, Baltimore, MD USA. [Esmat, Gamal E.] Cairo Univ, Cairo, Egypt. 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 75 BP 40A EP 41A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493800076 ER PT J AU Alonso, EM Ye, W Hawthorne, K Venkat, VL Loomes, KM Mack, CL Hertel, PM Karpen, SJ Kerkar, N Molleston, JP Murray, KF Romero, R Rosenthal, P Schwarz, KB Shneider, B Suchy, FJ Turmelle, YP Wang, KS Whitington, PF Sherker, AH Sokol, RJ Bezerra, JA Magee, JC AF Alonso, Estella M. Ye, Wen Hawthorne, Kieran Venkat, Veena L. Loomes, Kathleen M. Mack, Cara L. Hertel, Paula M. Karpen, Saul J. Kerkar, Nanda Molleston, Jean P. Murray, Karen F. Romero, Rene Rosenthal, Phil Schwarz, Kathleen B. Shneider, Benjamin Suchy, Frederick J. Turmelle, Yumirle P. Wang, Kasper S. Whitington, Peter F. Sherker, Averell H. Sokol, Ronald J. Bezerra, Jorge A. Magee, John C. TI Impact of Steroid Therapy on Early Growth in Infants with Biliary Atresia SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Alonso, Estella M.; Whitington, Peter F.] Ann & Robert H Lurie Childrens Hosp, Div Pediat Gastroenterol Hepatol & Nutr, Chicago, IL USA. [Ye, Wen] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Hawthorne, Kieran] Arbor Res Collaborat Hlth, Ann Arbor, MI USA. [Venkat, Veena L.] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. [Loomes, Kathleen M.] Childrens Hosp Philadelphia, Pediat Gastroenterol Hepatol & Nutr, Philadelphia, PA 19104 USA. [Mack, Cara L.; Suchy, Frederick J.; Sokol, Ronald J.] Univ Colorado, Sch Med, Sect Pediat Gastroenterol Hepatol & Nutr, Aurora, CO USA. [Hertel, Paula M.; Shneider, Benjamin] Baylor Coll Med, Pediat Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA. [Karpen, Saul J.; Romero, Rene] Emory Univ, Sch Med, Childrens Healthcare Atlanta, Pediat Gastroenterol Hepatol & Nutr, Atlanta, GA USA. [Kerkar, Nanda; Wang, Kasper S.] Childrens Hosp Los Angeles, Div Pediat Surg, Los Angeles, CA 90027 USA. [Molleston, Jean P.] Indiana Univ Sch Med, Riley Hosp Children, Pediat Gastroenterol Hepatol & Nutr, Indianapolis, IN 46202 USA. [Murray, Karen F.] Univ Washington, Med Ctr, Seattle Childrens, Div Gastroenterol & Hepatol, Seattle, WA 98195 USA. [Rosenthal, Phil] Univ Calif San Francisco, Dept Pediat, Div Gastroenterol Hepatol & Nutr, San Francisco, CA USA. [Schwarz, Kathleen B.] Johns Hopkins Sch Med, Baltimore, MD USA. [Turmelle, Yumirle P.] Washington Univ, Sch Med, St Louis, MO USA. [Sherker, Averell H.] NIDDKD, NIH, Bethesda, MD USA. [Bezerra, Jorge A.] Cincinnati Childrens Hosp Med, Div Pediat Gastroenterol Hepatol & Nutr, Cincinnati, OH USA. [Magee, John C.] Univ Michigan, Sch Med, Ann Arbor, MI 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 79 BP 43A EP 43A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493800080 ER PT J AU Murray, KF Rodriguez-Baez, N Kleiner, DE Shaffer, M Cooper, KL Ling, SC Rosenthal, P Schwarz, KB Schwarzenberg, SJ AF Murray, Karen F. Rodriguez-Baez, Norberto Kleiner, David E. Shaffer, Michele Cooper, Kara L. Ling, Simon C. Rosenthal, Philip Schwarz, Kathleen B. Schwarzenberg, Sarah J. TI Liver Histology in North American Children with Immune-active Chronic Hepatitis B Infection SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Murray, Karen F.; Shaffer, Michele; Cooper, Kara L.] Univ Washington, Med Ctr, Div Pediat GI & Hepatol, Seattle, WA 98195 USA. [Rodriguez-Baez, Norberto] Univ Texas Dallas, Pediatr Gastroenterol, Dallas, TX USA. [Kleiner, David E.] NCI, Pathol, Washington, DC USA. [Ling, Simon C.] Hosp Sick Kids, Pediat Gastroenterol & Hepatol, Toronto, ON, Canada. [Rosenthal, Philip] Univ Calif San Fransisco, Pediat Gastroenterol, San Francisco, CA USA. [Schwarz, Kathleen B.] Johns Hopkins Sch Med, Pediat Gastroenterol, Baltimore, MD USA. [Schwarzenberg, Sarah J.] Univ Minnesota, Pediat Gastroenterol, Minneapolis, MN 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 105 BP 57A EP 57A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493800106 ER PT J AU Chalasani, NP Ghabril, M Fontana, RJ Barnhart, HX Hayashi, PH Ahmad, J Stolz, A Navarro, VJ Hoofnagle, JH AF Chalasani, Naga P. Ghabril, Marwan Fontana, Robert J. Barnhart, Huiman X. Hayashi, Paul H. Ahmad, Jawad Stolz, Andrew Navarro, Victor J. Hoofnagle, Jay H. TI Idiosyncratic drug induced liver injury in African Americans: Causes, Clinical Features and Outcomes SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Chalasani, Naga P.; Ghabril, Marwan] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Fontana, Robert J.] Univ Michigan, Ann Arbor, MI 48109 USA. [Barnhart, Huiman X.] Duke Univ, Med Ctr, Durham, NC USA. [Hayashi, Paul H.] Univ N Carolina, Chapel Hill, NC USA. [Ahmad, Jawad] Icahn Sch Med Mt Sinai, Med Ctr, New York, NY 10029 USA. [Stolz, Andrew] Univ Southern Calif, Los Angeles, CA USA. [Navarro, Victor J.] Einstein Healthcare Network, Philadelphia, PA USA. [Hoofnagle, Jay H.] NIDDK, NIH, Bethesda, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 116 BP 64A EP 64A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493800117 ER PT J AU Ahmad, J Rossi, S Rodgers, SK Fontana, RJ Chalasani, NP Stolz, A Hayashi, PH Barnhart, HX Kleiner, DE Bjornsson, E AF Ahmad, Jawad Rossi, Simona Rodgers, Shuchi K. Fontana, Robert J. Chalasani, Naga P. Stolz, Andrew Hayashi, Paul H. Barnhart, Huiman X. Kleiner, David E. Bjornsson, Einar TI Drug Induced Liver Injury Associated with Sclerosing Cholangitis Like Changes on Magnetic Resonance Cholangiography Imaging SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Ahmad, Jawad] Icahn Sch Med Mt Sinai, Div Liver Dis, New York, NY 10029 USA. [Rossi, Simona] Einstein Med Ctr, Philadelphia, PA USA. [Rodgers, Shuchi K.] Einstein Med Ctr, Dept Radiol, Philadelphia, PA USA. [Fontana, Robert J.] Univ Michigan, Ann Arbor, MI 48109 USA. [Chalasani, Naga P.] Indiana Univ, Indianapolis, IN 46204 USA. [Stolz, Andrew] Univ Southern Calif, Los Angeles, CA USA. [Hayashi, Paul H.] Univ N Carolina, Chapel Hill, NC USA. [Barnhart, Huiman X.] Duke Univ, Durham, NC USA. [Kleiner, David E.] NCI, Bethesda, MD 20892 USA. [Bjornsson, Einar] Landspitali Univ Hosp, Reykjavik, Iceland. 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 118 BP 65A EP 65A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493800119 ER PT J AU Chalasani, NP Xu, YF de Boer, YS Raman, I Lian, Y Eckert, G Li, QZ Hoofnagle, JH AF Chalasani, Naga P. Xu, Yuanfang de Boer, Ynto S. Raman, Indu Lian, Yun Eckert, George Li, Quanzhen Hoofnagle, Jay H. TI Serum Ig M autoantibody profiling using autoantigen arrays identifies Histone H4 Ig M antibody as highly specific to patients with autoimmune like drug induced liver injury SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Chalasani, Naga P.; Xu, Yuanfang; Eckert, George] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Raman, Indu; Lian, Yun; Li, Quanzhen] Univ Texas Southwestern Med Ctr Dallas, Dallas, TX 75390 USA. [de Boer, Ynto S.] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [Hoofnagle, Jay H.] NIDDK, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 119 BP 65A EP 66A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493800120 ER PT J AU Gawrieh, S Karns, R Kleiner, DE Goldblatt, MI Olivier, M Chalasani, NP Xanthakos, S AF Gawrieh, Samer Karns, Rebekah Kleiner, David E. Goldblatt, Matthew I. Olivier, Michael Chalasani, Naga P. Xanthakos, Stavra TI Comparative analysis of global hepatic gene expression profiles in adolescents and adults with NAFLD SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Gawrieh, Samer; Chalasani, Naga P.] Indiana Univ Sch Med, Div Gastroenterol & Hepatol, Indianapolis, IN 46202 USA. [Olivier, Michael] Texax Biomed Inst, Genet, San Antonio, TX USA. [Karns, Rebekah] Cincinnati Children Hosp, Bioinformat, Cincinnati, OH USA. [Kleiner, David E.] NCI, Pathol Lab, Bldg 10, Bethesda, MD 20892 USA. [Goldblatt, Matthew I.] Med Coll Wisconsin, Surg, Milwaukee, WI 53226 USA. [Xanthakos, Stavra] Cincinnati Children Hosp, Div Gastroenterol & Hepatol, Cincinnati, OH 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 199 BP 105A EP 105A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493800200 ER PT J AU Chen, JG Odena, G Xu, MJ Rodrigo, D Altamirano, J Massey, VL Affo, S Cabezas, J Gines, P Caballeria, J Sancho-Bru, P Gao, B Bataller, R AF Chen, Jiegen Odena, Gemma Xu, Ming-Jiang Rodrigo, Daniel Altamirano, Jose Massey, Veronica L. Affo, Silvia Cabezas, Joaquin Gines, Pere Caballeria, Juan Sancho-Bru, Pau Gao, Bin Bataller, Ramon TI Lipocalin-2 overexpression is mediated by LPS-TL4 pathway and mediates liver fibrosis in alcoholic hepatitis SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Chen, Jiegen; Odena, Gemma; Massey, Veronica L.; Cabezas, Joaquin; Bataller, Ramon] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Chen, Jiegen; Odena, Gemma; Massey, Veronica L.; Cabezas, Joaquin; Bataller, Ramon] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. [Chen, Jiegen; Odena, Gemma; Massey, Veronica L.; Cabezas, Joaquin; Bataller, Ramon] Univ N Carolina, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. [Xu, Ming-Jiang; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA. [Rodrigo, Daniel; Affo, Silvia; Gines, Pere; Caballeria, Juan; Sancho-Bru, Pau] CIBER Enfermedades Hepat & Digest CIBERehd, Inst INvest Biomed August Pi & Sunyer IDIBAPS, Hosp Clin, Barcelona, Spain. [Altamirano, Jose] Univ Autonoma Barcelona, Vall dHebron Hosp, Dept Internal Med, Liver Unit, Barcelona, Spain. [Altamirano, Jose] Univ Autonoma Barcelona, Vall dHebron Inst Recerca VHIR, Barcelona, Spain. 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 219 BP 116A EP 116A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493800220 ER PT J AU Han, MAT Samala, N Rizvi, BS Etzion, O Wright, EC Patel, R Samala-Venkata, V Kleiner, DE Koh, C Pavletic, S Williams, K Heller, T AF Han, Ma Ai Thanda Samala, Niharika Rizvi, Bisharah S. Etzion, Ohad Wright, Elizabeth C. Patel, Ruchi Samala-Venkata, Vikramaditya Kleiner, David E. Koh, Christopher Pavletic, Steven Williams, Kirsten Heller, Theo TI Abnormal Liver Tests Are Inaccurate For Diagnosis Of Chronic Hepatic Graft Versus Host Disease In Critically Ill Patients SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Han, Ma Ai Thanda; Samala, Niharika; Rizvi, Bisharah S.; Etzion, Ohad; Patel, Ruchi; Samala-Venkata, Vikramaditya; Koh, Christopher; Heller, Theo] NIDDK, Liver Dis Branch, NIH, Rockville, MD USA. [Wright, Elizabeth C.] NIDDK, NIH, Bethesda, MD 20892 USA. [Kleiner, David E.; Pavletic, Steven; Williams, Kirsten] NCI, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 356 BP 182A EP 182A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493801098 ER PT J AU Bae, H Hodge, D Yang, GX Leung, PS Valencia, J Tsuneyama, K Gershwin, ME Young, HA AF Bae, Heekyong Hodge, Deborah Yang, Guo-Xiang Leung, Patrick S. Valencia, Julio Tsuneyama, Koichi Gershwin, M. Eric Young, Howard A. TI The interplay of type I and type II interferons in murine autoimmune cholangitis as a basis for sex-biased autoimmunity SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Bae, Heekyong; Hodge, Deborah; Valencia, Julio; Young, Howard A.] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA. [Yang, Guo-Xiang; Leung, Patrick S.; Gershwin, M. Eric] Univ Calif Davis, Sch Med, Div Rheumatol Allergy & Clin Immunol, Davis, CA 95616 USA. [Tsuneyama, Koichi] Univ Tokushima, Grad Sch, Dept Pathol & Lab Med, Tokushima, Japan. 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 364 BP 186A EP 186A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493801106 ER PT J AU Roberts, LR Farshidfar, F Zheng, SY Gingras, MC Newton, Y Shih, J Robertson, AG Hinoue, T Hoadley, KA Gibbs, R Roszik, J Covington, K Wu, CC Shinbrot, E Stransky, N Hegde, AM Yang, JD Reznik, E Sadeghi, S Pedamallu, CS Ojesina, AI Hess, J Auman, JT Rhie, SK Bowlby, R Borad, MJ Stuart, J Sander, C Akbani, R Cherniack, AD Laird, PW Deshpande, V Mounajjed, T Foo, WC Torbenson, M Kleiner, DE Wheeler, DA Mcree, AJ Bathe, OF Andersen, JB Bardeesy, N Kwong, LN AF Roberts, Lewis R. Farshidfar, Farshad Zheng, Siyuan Gingras, Marie-Claude Newton, Yulia Shih, Juliann Robertson, A. Gordon Hinoue, Toshinori Hoadley, Katherine A. Gibbs, Richard Roszik, Jason Covington, Kyle Wu, Chia-Chin Shinbrot, Eve Stransky, Nicolas Hegde, Apurva M. Yang, Ju Dong Reznik, Ed Sadeghi, Sara Pedamallu, Chandra Sekhar Ojesina, Akinyemi I. Hess, Julian Auman, J. Todd Rhie, Suhn K. Bowlby, Reanne Borad, Mitesh J. Stuart, Josh Sander, Chris Akbani, Rehan Cherniack, Andrew D. Laird, Peter W. Deshpande, Vikram Mounajjed, Taofic Foo, Wai Chin Torbenson, Michael Kleiner, David E. Wheeler, David A. Mcree, Autumn J. Bathe, Oliver F. Andersen, Jesper B. Bardeesy, Nabeel Kwong, Lawrence N. TI Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Roberts, Lewis R.; Yang, Ju Dong; Mounajjed, Taofic; Torbenson, Michael] Mayo Clin, Coll Med, Rochester, MN USA. [Farshidfar, Farshad] Univ Calgary, Calgary, AB, Canada. [Zheng, Siyuan; Roszik, Jason; Wu, Chia-Chin; Hegde, Apurva M.; Akbani, Rehan; Foo, Wai Chin; Kwong, Lawrence N.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Gingras, Marie-Claude; Gibbs, Richard; Covington, Kyle; Shinbrot, Eve; Wheeler, David A.] Baylor Coll Med, Houston, TX 77030 USA. [Newton, Yulia; Stuart, Josh] Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA. [Shih, Juliann; Cherniack, Andrew D.] Eli & Edythe L Broad Inst Massachusetts Inst Tech, Cambridge, MA USA. [Robertson, A. Gordon; Sadeghi, Sara; Bowlby, Reanne] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC, Canada. [Hinoue, Toshinori; Laird, Peter W.] Van Andel Res Inst, Grand Rapids, MI USA. [Hoadley, Katherine A.; Auman, J. Todd; Mcree, Autumn J.] Univ North Carolina Chapel Hill, Chapel Hill, NC USA. [Stransky, Nicolas] Blueprint Med, Cambridge, MA USA. [Reznik, Ed] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Pedamallu, Chandra Sekhar; Sander, Chris] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ojesina, Akinyemi I.] Univ Alabama Birmingham, Birmingham, AL USA. [Rhie, Suhn K.] Univ Southern Calif, Los Angeles, CA USA. [Borad, Mitesh J.] Mayo Clin, Scottsdale, AZ USA. [Kleiner, David E.] NCI, Bethesda, MD 20892 USA. [Bathe, Oliver F.] Tom Baker Canc Clin, Calgary, AB, Canada. [Andersen, Jesper B.] Univ Copenhagen, DK-1168 Copenhagen, Denmark. [Bardeesy, Nabeel] Harvard Med Sch, Ctr Canc, Gen Hosp 1Massachusetts, Boston, MA USA. [Hess, Julian] Broad Inst, Cambridge, MA USA. [Deshpande, Vikram] Massachusetts Gen Hosp, Boston, MA 02114 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 447 BP 227A EP 227A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493801189 ER PT J AU Castven, D Czauderna, C Becker, D Worns, MA Grimminger, P Lang, H Thorgeirsson, SS Galle, PR Marquardt, JU AF Castven, Darko Czauderna, Carolin Becker, Diana Worns, Marcus A. Grimminger, Peter Lang, Hauke Thorgeirsson, Snorri S. Galle, Peter R. Marquardt, Jens U. TI Importance of Stem-like Tumor-initiating Cells for the Development of Chemoresistance During Anti-angiogenic Therapies in Hepatocellular Carcinoma SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Castven, Darko; Czauderna, Carolin; Becker, Diana; Worns, Marcus A.; Galle, Peter R.; Marquardt, Jens U.] Johannes Gutenberg Univ Mainz, Dept Internal Med, Mainz, Germany. [Thorgeirsson, Snorri S.] NCI, CCR, NIH, Bethesda, MD 20892 USA. [Grimminger, Peter] Johannes Gutenberg Univ Mainz, Dept Surg, Mainz, Germany. 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 494 BP 250A EP 250A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493801236 ER PT J AU An, P Zeng, Z Winkler, CA AF An, Ping Zeng, Zheng Winkler, Cheryl A. TI The loss-of-function S267F variant in the HBV receptor NTCP reduces human risk to HBV infection SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [An, Ping; Winkler, Cheryl A.] NCI, Basic Res Lab, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA. [Zeng, Zheng] Peking Univ, Dept Infect Dis, Hosp 1, Beijing, Peoples R China. 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 602 BP 300A EP 300A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493801342 ER PT J AU Zhang, Q Matsuura, K Kleiner, DE Zamboni, F Alter, HJ Farci, P AF Zhang, Quan Matsuura, Kentaro Kleiner, David E. Zamboni, Fausto Alter, Harvey J. Farci, Patrizia TI Identification of Long Noncoding RNA Associated with Hepatocellular Carcinoma of Different Viral Etiology SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Zhang, Quan; Farci, Patrizia] NIH, Infect Dis Lab, Bldg 10, Bethesda, MD 20892 USA. [Matsuura, Kentaro; Alter, Harvey J.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Kleiner, David E.] NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. [Zamboni, Fausto] Brotzu Hosp, Liver Transplantat Ctr, Cagliari, Italy. 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 609 BP 303A EP 304A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493801349 ER PT J AU Townsend, EC Moon, MS Zhang, G Firke, M Han, MAT Kleiner, DE Koh, C Heller, T AF Townsend, Elizabeth C. Moon, Mi Sun Zhang, Grace Firke, Marian Han, Ma Ai Thanda Kleiner, David E. Koh, Christopher Heller, Theo TI Microbial Translocation in the Context of Hepatitis B and Hepatitis D infection SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Townsend, Elizabeth C.; Moon, Mi Sun; Zhang, Grace; Firke, Marian; Han, Ma Ai Thanda; Koh, Christopher; Heller, Theo] NIH, Liver Dis Branch, Bldg 10, Bethesda, MD 20892 USA. [Kleiner, David E.] NCI, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 627 BP 312A EP 313A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493801367 ER PT J AU Tillmann, HL Barnhart, HX Serrano, J Rockey, DC AF Tillmann, Hans L. Barnhart, Huiman X. Serrano, Jose Rockey, Don C. TI A Novel Computerized Drug Induced Liver Injury Causality Assessment Tool (DILI-CAT) SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Tillmann, Hans L.] East Carolina Univ, Dept Med, Div Gastroenterol Hepatol & Nutr, Greenville, NC USA. [Barnhart, Huiman X.] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Serrano, Jose] NIDDK, Digest Dis Branch, Bethesda, DC USA. [Rockey, Don C.] Med Univ South Carolina, Med, Charleston, SC 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 645 BP 320A EP 321A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493801385 ER PT J AU Amet, T Li, W Yang, D Liangpunsakul, S Puri, P Kamath, PS Sanyal, AJ Shah, V Radaeva, S Crabb, DW Chalasani, NP Yu, QA AF Amet, Tohti Li, Wei Yang, Dennis Liangpunsakul, Suthat Puri, Puneet Kamath, Patrick S. Sanyal, Arun J. Shah, Vijay Radaeva, Svetlana Crabb, David W. Chalasani, Naga P. Yu, Qigui A. TI Profiles of inflammatory cytokines/chemokines and immune cell activation in patients with alcoholic hepatitis SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Amet, Tohti; Li, Wei; Yang, Dennis; Yu, Qigui A.] Indiana Univ Sch Med, Microbiol & Immunol, Indianapolis, IN 46202 USA. [Liangpunsakul, Suthat; Crabb, David W.; Chalasani, Naga P.] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA. [Puri, Puneet; Sanyal, Arun J.] Virginia Commonwealth Univ, Richmond, VA USA. [Kamath, Patrick S.; Shah, Vijay] Mayo Clin, Rochester, MN USA. [Radaeva, Svetlana] NIAAA, Bethesda, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 689 BP 341A EP 342A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493801429 ER PT J AU Vatsalya, V Song, M Schwandt, M Cave, M Barve, S George, D Ramchandani, VA McClain, C AF Vatsalya, Vatsalya Song, Ming Schwandt, Melanie Cave, Matthew Barve, Shirish George, David Ramchandani, Vijay A. McClain, Craig TI Effects of sex, drinking history and omega-3 and omega-6 fatty acids dysregulation on the onset of liver injury in very heavy drinking alcohol dependent patients SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Vatsalya, Vatsalya; Song, Ming; Cave, Matthew; Barve, Shirish; McClain, Craig] Univ Louisville, Med, Louisville, KY 40292 USA. [Schwandt, Melanie; George, David; Ramchandani, Vijay A.] NIAAA, DICBR LCTS, Bethesda, MD 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 688 BP 341A EP 341A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493801428 ER PT J AU Li, W Amet, T Yang, K Liangpunsakul, S Puri, P Kamath, PS Sanyal, AJ Shah, V Radaeva, S Crabb, DW Chalasani, NP Yu, QA AF Li, Wei Amet, Tohti Yang, Kai Liangpunsakul, Suthat Puri, Puneet Kamath, Patrick S. Sanyal, Arun J. Shah, Vijay Radaeva, Svetlana Crabb, David W. Chalasani, Naga P. Yu, Qigui A. TI Monocyte/macrophage activation and IL-22 dysregulation in patients with alcoholic hepatitis SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Li, Wei; Amet, Tohti; Yang, Kai; Yu, Qigui A.] Indiana Univ Sch Med, Microbiol & Immunol, Indianapolis, IN 46202 USA. [Liangpunsakul, Suthat; Crabb, David W.; Chalasani, Naga P.] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA. [Puri, Puneet; Sanyal, Arun J.] Virginia Commonwealth Univ, Richmond, VA USA. [Kamath, Patrick S.; Shah, Vijay] Mayo Clin, Rochester, MN USA. [Radaeva, Svetlana] NIAAA, Bethesda, MD 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 696 BP 344A EP 345A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493801436 ER PT J AU Etzion, O Ali, R Koh, C Levy, E Kleiner, DE Rampertaap, S Rosenzweig, S Takyar, VK Han, MAT Lingala, S Fryzek, N Haynes-Williams, V Heller, T AF Etzion, Ohad Ali, Rabab Koh, Christopher Levy, Elliot Kleiner, David E. Rampertaap, Shakuntala Rosenzweig, Sergio Takyar, Varun K. Han, Ma Ai Thanda Lingala, Shilpa Fryzek, Nancy Haynes-Williams, Vanessa Heller, Theo TI Disparate Changes in Adaptive Immunity in Systemic vs. Portal Venous Circulation, Across the Spectrum of HCV Associated Liver Disease SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Kleiner, David E.] NCI, Pathol Lab, Bldg 10, Bethesda, MD 20892 USA. [Etzion, Ohad; Ali, Rabab; Koh, Christopher; Levy, Elliot; Kleiner, David E.; Rampertaap, Shakuntala; Rosenzweig, Sergio; Takyar, Varun K.; Han, Ma Ai Thanda; Lingala, Shilpa; Fryzek, Nancy; Haynes-Williams, Vanessa; Heller, Theo] NIH, Bldg 10, Bethesda, MD 20892 USA. [Etzion, Ohad; Ali, Rabab; Koh, Christopher; Takyar, Varun K.; Han, Ma Ai Thanda; Lingala, Shilpa; Fryzek, Nancy; Haynes-Williams, Vanessa; Heller, Theo] NIDDK, Liver Dis Branch, Bethesda, MD 20892 USA. [Levy, Elliot] Ctr Clin, Intervent Radiol, Bethesda, MD USA. [Rampertaap, Shakuntala; Rosenzweig, Sergio] Ctr Clin, Immunol Serv, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 731 BP 362A EP 362A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493802003 ER PT J AU Unalp-Arida, A Ruhl, CE AF Unalp-Arida, Aynur Ruhl, Constance E. TI The Burden of Viral Hepatitis B and C Infection in the United States Population SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Unalp-Arida, Aynur] NIDDK, Bethesda, MD 20892 USA. [Ruhl, Constance E.] Social & Sci Syst Inc, Silver Spring, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 793 BP 391A EP 391A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493802062 ER PT J AU Naggie, S Rosenthal, E Kattakuzhy, S McGinnis, J Naik, S Natha, M Llewellyn, J Haubrich, R Osinusi, AO Stamm, LM Cooper, C Dieterich, DT Sulkowski, MS AF Naggie, Susanna Rosenthal, Eric Kattakuzhy, Sarah McGinnis, Justin Naik, Sarjita Natha, Macky Llewellyn, Joseph Haubrich, Richard Osinusi, Anu O. Stamm, Luisa M. Cooper, Curtis Dieterich, Douglas T. Sulkowski, Mark S. TI Real World Effectiveness of Ledipasvir/Sofosbuvir (LDV/SOF) in Patients Coinfected With HCV and HIV-1: A Comparative Analysis of Clinical Trials with Four Real World Cohorts SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Naggie, Susanna] Duke Univ, Durham, NC USA. [Rosenthal, Eric] Univ Hosp Archet, Nice, France. [Kattakuzhy, Sarah] NIH, Rockville, MD USA. [McGinnis, Justin] Univ Southern Calif, Los Angeles, CA USA. [Naik, Sarjita; Natha, Macky; Llewellyn, Joseph; Haubrich, Richard; Osinusi, Anu O.; Stamm, Luisa M.] Gilead Sci, Foster City, CA USA. [Cooper, Curtis] Ottawa Hosp, Ottawa, ON, Canada. [Dieterich, Douglas T.] Mt Sinai Sch Med, New York, NY USA. [Sulkowski, Mark S.] Johns Hopkins Univ, Baltimore, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 892 BP 445A EP 445A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493802159 ER PT J AU Tran, NJQ Kovalic, AJ Kleiner, DE Bridges, D Satapathy, SK AF Tran, Nhu Josephine Q. Kovalic, Alexander J. Kleiner, David E. Bridges, Dave Satapathy, Sanjaya K. TI The use of calcineurin inhibitors post-liver transplantation and the donor SOD2 C47T polymorphism influence recurrent NAFLD after liver transplantation SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Tran, Nhu Josephine Q.] Univ Tennessee, Ctr Hlth Sci, Prevent Med, Memphis, TN 38163 USA. [Bridges, Dave] Univ Tennessee, Ctr Hlth Sci, Physiol, Memphis, TN 38163 USA. [Satapathy, Sanjaya K.] Univ Tennessee, Ctr Hlth Sci, Surg, Memphis, TN 38163 USA. [Satapathy, Sanjaya K.] Methodist Univ Hosp, Transplant Inst, Memphis, TN USA. [Kovalic, Alexander J.] Univ Tennessee, Ctr Hlth Sci, Med, Memphis, TN 38163 USA. [Kleiner, David E.] NIH, Baltimore, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 990 BP 502A EP 502A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493802257 ER PT J AU Bolte, FJ O'Keefe, A Etzion, O Ali, R Serti, E Liang, TJ Heller, T Rehermann, B AF Bolte, Fabian J. O'Keefe, Ashley Etzion, Ohad Ali, Rabab Serti, Elisavet Liang, T. Jake Heller, Theo Rehermann, Barbara TI Innate immune cell phenotype and function in different compartments of the gut-liver-axis in chronic liver diseas SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Bolte, Fabian J.; O'Keefe, Ashley; Etzion, Ohad; Ali, Rabab; Serti, Elisavet; Liang, T. Jake; Heller, Theo; Rehermann, Barbara] NIDDK, Liver Dis Branch, NIH, DHHS, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1029 BP 520A EP 520A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493802296 ER PT J AU Ouyang, XS Han, SN Lau, G Feng, DC Cardone, R Cai, SY Hoque, R Chen, YL Yang, WH Garcia-Martinez, I Wang, FS Gao, B Torok, NJ Kibbey, R Mehal, WZ AF Ouyang, Xinshou Han, Sheng-Na Lau, George Feng, Dechun Cardone, Rebecca Cai, Shi-Ying Hoque, Rafaz Chen, Yonglin Yang, Wei-Hong Garcia-Martinez, Irma Wang, Fu-Sheng Gao, Bin Torok, Natalie J. Kibbey, Richard Mehal, Wajahat Z. TI Digoxin protects from sterile inflammation in the liver by targeting pyruvate kinase M2 (PKM2) promoted HIF-1 alpha transactivation SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Ouyang, Xinshou; Han, Sheng-Na; Lau, George; Cardone, Rebecca; Cai, Shi-Ying; Hoque, Rafaz; Chen, Yonglin; Yang, Wei-Hong; Garcia-Martinez, Irma; Kibbey, Richard; Mehal, Wajahat Z.] Yale Univ, New Haven, CT USA. [Feng, Dechun; Gao, Bin] NIAAA, NIH, Bethesda, MD USA. [Wang, Fu-Sheng] Beijing 302 Hosp, Inst Translat Hepatol, Beijing, Peoples R China. [Torok, Natalie J.] Univ Calif Davis, Dept Med, Sacramento, CA 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1035 BP 522A EP 523A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493802302 ER PT J AU Samala, N Hallinan, EK Kleiner, DE Hoofnagle, JH Loomba, R AF Samala, Niharika Hallinan, Erin K. Kleiner, David E. Hoofnagle, Jay H. Loomba, Rohit TI Race and Ethnicity in Patients with Nonalcoholic Fatty Liver Disease SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Hoofnagle, Jay H.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Samala, Niharika] Indiana Univ Sch Med, Med, Indianapolis, IN 46202 USA. [Hallinan, Erin K.] John Hopkins Univ Bloomberg Sch Publ Hlth, Stat, Indianapolis, IN USA. [Kleiner, David E.] NCI, Pathol, NIH, Indianapolis, IN USA. [Loomba, Rohit] Univ Calif San Diego, Med, Indianapolis, IN 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1055 BP 532A EP 532A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493802322 ER PT J AU Unalp-Arida, A Ruhl, CE AF Unalp-Arida, Aynur Ruhl, Constance E. TI The US Fatty Liver Index and Fatty Liver Index as Potential Steatosis Markers Predict Liver Disease Mortality in the US Population SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Unalp-Arida, Aynur] NIDDK, Bethesda, MD 20892 USA. [Ruhl, Constance E.] Social & Sci Syst Inc, Silver Spring, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1059 BP 533A EP 534A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493802326 ER PT J AU Unalp-Arida, A Ruhl, CE AF Unalp-Arida, Aynur Ruhl, Constance E. TI The Burden of Liver Disease in the United States Population SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Unalp-Arida, Aynur] NIDDK, Bethesda, MD 20892 USA. [Ruhl, Constance E.] Social & Sci Syst Inc, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1115 BP 563A EP 563A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493802382 ER PT J AU Rotman, Y Lingala, S Morris, N AF Rotman, Yaron Lingala, Shilpa Morris, Nevitt TI Subtle Iron Deficiency is Common During Vitamin E Treatment For NAFLD SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Rotman, Yaron; Lingala, Shilpa; Morris, Nevitt] NIDDK, Liver & Energy Metab Unit, Liver Dis Branch, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1133 BP 571A EP 572A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493802400 ER PT J AU Takyar, VK Nath, A Beri, A Rotman, Y AF Takyar, Varun K. Nath, Anand Beri, Andrea Rotman, Yaron TI How Healthy are "Healthy Volunteers"? Prevalence and Potential Impact of Fatty Liver Disease in Volunteers to Clinical Trials SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Takyar, Varun K.; Nath, Anand; Rotman, Yaron] NIDDK, Liver & Energy Metab Unit, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Nath, Anand] Georgetown Univ, Sch Med, Medstar Washington Hosp Ctr, Dept Internal Med, Washington, DC USA. [Beri, Andrea] NIH, BTRIS, Lab Informat Dev, Ctr Clin, Bldg 10, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1157 BP 583A EP 583A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493802424 ER PT J AU Serti, E Werner, JM Keane, M Bolte, FJ Lingala, S Morris, N Liang, TJ Rotman, Y Rehermann, B AF Serti, Elisavet Werner, Jens M. Keane, Meghan Bolte, Fabian J. Lingala, Shilpa Morris, Nevitt Liang, T. Jake Rotman, Yaron Rehermann, Barbara TI Natural killer T cells and mucosal associated invariant T cells share phenotypic and functional alterations in patients with non-alcoholic fatty liver disease SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Serti, Elisavet; Werner, Jens M.; Keane, Meghan; Bolte, Fabian J.; Lingala, Shilpa; Morris, Nevitt; Liang, T. Jake; Rotman, Yaron; Rehermann, Barbara] NIDDK, Liver Dis Branch, NIH, DHHS, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1160 BP 584A EP 584A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493802427 ER PT J AU Sampaziotis, F de Brito, MC Sawiak, S Gomez-Vazquez, MJ Berntsen, NL Tysoe, OC Ortmann, D Bertero, A Bargehr, J Zonneveld, MC Pedersen, MT Pawlowski, M Georgakopoulos, N Yiangou, L Godfrey, EM Upponi, SS Gieseck, R Rimland, C Simonic, I Davies, S Jensen, KB Sinha, S Gelson, W Alexander, GJ Melum, E Hannan, NR Saeb-Parsy, K Vallier, L AF Sampaziotis, Fotios de Brito, Miguel Cardoso Sawiak, Steve Gomez-Vazquez, Maria J. Berntsen, Natalie L. Tysoe, Olivia C. Ortmann, Daniel Bertero, Alessandro Bargehr, Johannes Zonneveld, Marielle C. Pedersen, Marianne T. Pawlowski, Matthias Georgakopoulos, Nikitas Yiangou, Loukia Godfrey, Edmund M. Upponi, Sara S. Gieseck, Richard Rimland, Casey Simonic, Ingrid Davies, Susan Jensen, Kim B. Sinha, Sanjay Gelson, William Alexander, Graeme J. Melum, Espen Hannan, Nicholas R. Saeb-Parsy, Kourosh Vallier, Ludovic TI Reconstruction of the biliary tree using primary in vitro propagated extra-hepatic cholangiocytes and biode-gradable scaffolds SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Sampaziotis, Fotios] Cambridge Univ Hosp NHS Fdn Trust, Hepatol, Hitchin, England. [Sampaziotis, Fotios; de Brito, Miguel Cardoso; Tysoe, Olivia C.; Ortmann, Daniel; Bertero, Alessandro; Zonneveld, Marielle C.; Georgakopoulos, Nikitas; Yiangou, Loukia; Rimland, Casey; Saeb-Parsy, Kourosh; Vallier, Ludovic] Univ Cambridge, Surg, Cambridge, England. [Sawiak, Steve] Univ Cambridge, Clin Neurosci, Cambridge, England. [Gomez-Vazquez, Maria J.] Univ Cambridge, Pathol, Cambridge, England. [Bargehr, Johannes; Pawlowski, Matthias; Sinha, Sanjay; Alexander, Graeme J.] Univ Cambridge, Med, Cambridge, England. [Pedersen, Marianne T.; Jensen, Kim B.] Univ Copenhagen, Biotech Res & Innovat Ctr, Copenhagen, Denmark. [Godfrey, Edmund M.; Upponi, Sara S.] Cambridge Univ Hosp NHS Fdn Trust, Radiol, Cambridge, England. [Gieseck, Richard] NIAID, Parasit Dis Lab, Bethesda, MD USA. [Simonic, Ingrid] Cambridge Univ Hosp NHS Fdn Trust, Med Genet Labs, Cambridge, England. [Davies, Susan] Cambridge Univ Hosp NHS Fdn Trust, Histopathol, Cambridge, England. [Gelson, William] Cambridge Univ Hosp NHS Fdn Trust, Hepatol, Cambridge, England. [Melum, Espen] Natl Hosp Norway, Oslo Univ Hosp, Clin Specialized Med & Surg, Norwegian PSC Res Ctr, Oslo, Norway. [Hannan, Nicholas R.] Univ Nottingham, Ctr Biomol Sci, Nottingham, England. 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1187 BP 597A EP 598A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493802454 ER PT J AU Puri, P Daita, K Mirshahi, F Liangpunsakul, S Chalasani, NP Crabb, DW Shah, V Kamath, PS Gores, GJ Katz, BP Sikaroodi, M Radaeva, S Gillevet, PM Sanyal, AJ AF Puri, Puneet Daita, Kalyani Mirshahi, Faridoddin Liangpunsakul, Suthat Chalasani, Naga P. Crabb, David W. Shah, Vijay Kamath, Patrick S. Gores, Gregory J. Katz, Barry P. Sikaroodi, Masoumeh Radaeva, Svetlana Gillevet, Patrick M. Sanyal, Arun J. TI Alcoholic Hepatitis and Disease Severity Are Associated With Distinct Shifts in Fecal Microbial Ecology SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Puri, Puneet; Daita, Kalyani; Mirshahi, Faridoddin; Sanyal, Arun J.] Virginia Commonwealth Univ, Richmond, VA USA. [Liangpunsakul, Suthat; Chalasani, Naga P.; Crabb, David W.; Katz, Barry P.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Shah, Vijay; Kamath, Patrick S.; Gores, Gregory J.] Mayo Clin, Rochester, MN USA. [Sikaroodi, Masoumeh; Gillevet, Patrick M.] George Mason Univ, Manassas, VA USA. [Radaeva, Svetlana] NIAAA, Bethesda, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1212 BP 609A EP 609A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493803019 ER PT J AU Unalp-Arida, A Ruhl, CE AF Unalp-Arida, Aynur Ruhl, Constance E. TI The Burden of Liver Cancer in the United States Population SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Unalp-Arida, Aynur] NIDDK, Bethesda, MD 20892 USA. [Ruhl, Constance E.] Social & Sci Syst Inc, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1278 BP 641A EP 642A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493803085 ER PT J AU Tang, MM Alao, H Morris, N Walter, M Rolman, Y AF Tang, Michele M. Alao, Hawwa Morris, Nevitt Walter, Mary Rolman, Yaron TI The Fatigue of Chronic Liver Disease is Associated with Altered Circadian Rhythm of Cortisol SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Tang, Michele M.; Alao, Hawwa; Morris, Nevitt; Rolman, Yaron] NIDDK, Liver & Energy Metab Unit, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Tang, Michele M.] Univ Calif San Francisco, Dept Med, Div Gastroenterol, San Francisco, CA USA. [Tang, Michele M.] Univ Calif San Francisco, UCSF Liver Transplant Ctr, San Francisco, CA 94143 USA. [Walter, Mary] NIDDK, Clin Res Core 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1446 BP 723A EP 724A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493803253 ER PT J AU Ramirez, T Lie, YM Yin, S Xu, MJ Feng, DC Zang, MW Pacher, P Gao, B Wang, H AF Ramirez, Teresa Lie, Yongmei Yin, Shi Xu, Ming-Jiang Feng, Dechun Zang, Mengwei Pacher, Pal Gao, Bin Wang, Hua TI Aging aggravates alcoholic liver injury and fibrosis in mice by downregulating Sirtuin 1 expressionin the liver SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Wang, Hua] Anhui Med Univ, Affiliated Prov Hosp, Dept Oncol, Hefei, Anhui, Peoples R China. [Ramirez, Teresa; Lie, Yongmei; Yin, Shi; Xu, Ming-Jiang; Feng, Dechun; Gao, Bin; Wang, Hua] NIAAA, Lab Liver Dis, NIH, Rockville, MD 20852 USA. [Zang, Mengwei] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Pacher, Pal] NIAAA, Lab Cardiovasc Physiol & Tissue Injury, Rockville, MD 20852 USA. RI Zhou, Zhou/R-7788-2016 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1513 BP 755A EP 755A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493803320 ER PT J AU Chen, HQ Li, Y Sherban, A Nocon, A Luo, T Wang, H Bin Gao, Zang, MW AF Chen, Hanqing Li, Yu Sherban, Alex Nocon, Allison Luo, Ting Wang, Hua Bin Gao Zang, Mengwei TI Pharmacological and Molecular inhibition of mTORC1 Activation Reduces Ethanol-Induced ER Stress and Ameliorates Alcoholic Liver Injury in Mice SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Chen, Hanqing; Li, Yu; Sherban, Alex; Nocon, Allison; Luo, Ting] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Wang, Hua; Bin Gao] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA. [Chen, Hanqing; Zang, Mengwei] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, Ctr Hlth Aging, San Antonio, TX 78229 USA. [Chen, Hanqing; Zang, Mengwei] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. [Zang, Mengwei] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1515 BP 756A EP 756A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493803322 ER PT J AU Abdelmegeed, M Choi, YS Song, BJ AF Abdelmegeed, Mohamed Choi, Youngshim Song, Byoung-Joon TI The role of cytochrome P450-2E1 in fast food-induced hepatic fibrosis SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Abdelmegeed, Mohamed; Choi, Youngshim; Song, Byoung-Joon] NIH, Membrane Biochem & Biophys, Rockville, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1546 BP 769A EP 770A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493803353 ER PT J AU Naguib, G Morris, N Bernstein, S Rotman, Y AF Naguib, Gihan Morris, Nevitt Bernstein, Shanna Rotman, Yaron TI NAFLD is Associated with Decreased Oxidation of Orally-Delivered Fatty Acids - a Palmitate Breath Test Study SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Naguib, Gihan; Morris, Nevitt; Rotman, Yaron] NIDDK, Liver & Energy Metab Unit, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Naguib, Gihan] Univ Maryland, Pediat Gastroenterol, Baltimore, MD 21201 USA. [Bernstein, Shanna] NIH, Dept Nutr, Ctr Clin, Bldg 10, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1562 BP 776A EP 776A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493803369 ER PT J AU Samala, N Ted, H Maloney, D Nadler, JL Chalasani, NP Mirmira, R Anderson, R AF Samala, Niharika Ted, Holman Maloney, David Nadler, Jerry L. Chalasani, Naga P. Mirmira, Raghavendra Anderson, Ryan TI Role of 12-Lipoxygenase in a Zebrafish Model of Non Alcoholic Fatty Liver Disease (NAFLD) SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Samala, Niharika; Chalasani, Naga P.; Mirmira, Raghavendra] Indiana Univ Sch Med, Med, Indianapolis, IN 46202 USA. [Ted, Holman] Univ Calif Santa Cruz, PBSci Chem & Biochem, Santa Cruz, CA 95064 USA. [Maloney, David] NIH, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA. [Anderson, Ryan] Indiana Univ Sch Med, Pediat, Indianapolis, IN 46202 USA. [Nadler, Jerry L.] Eastern Virginia Med Sch, Internal Med, Norfolk, VA 23501 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1566 BP 778A EP 778A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493803373 ER PT J AU Suarez, DF Loria, A Ferreira, M Raziuddin, A Ghany, MG AF Suarez, Daniel F. Loria, Anthony Ferreira, Michelle Raziuddin, Arati Ghany, Marc G. TI Proportion of Pre-Core Mutation Determines HBV Phenotype after HBeAg Seroconversion SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Suarez, Daniel F.; Loria, Anthony; Ferreira, Michelle; Ghany, Marc G.] NIH, Liver Dis Branch, Bldg 10, Bethesda, MD 20892 USA. [Raziuddin, Arati] NCI, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1831 BP 903A EP 903A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493804192 ER PT J AU Yurdaydin, C Idilman, R Kalkan, C Karakaya, F Kartal, AC Keskin, O Karatayli, E Karatayli, SC Bozdayi, AM Koh, C Heller, T Glenn, J AF Yurdaydin, Cihan Idilman, Ramazan Kalkan, Cagdas Karakaya, Fatih Kartal, Aysun Caliskan Keskin, Onur Karatayli, Ersin Karatayli, Senem C. Bozdayi, A. Mithat Koh, Christopher Heller, Theo Glenn, Jeffrey TI Exploring Optimal Dosing Of Lonafarnib With Ritonavir For The Treatment Of Chronic Delta Hepatitis-Interim Results From The Lowr Hdv-2 Study SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Yurdaydin, Cihan; Idilman, Ramazan; Kalkan, Cagdas; Karakaya, Fatih; Kartal, Aysun Caliskan; Keskin, Onur; Karatayli, Ersin; Karatayli, Senem C.; Bozdayi, A. Mithat] Ankara Univ, Sch Med, Gastroenterol Sect, Ankara, Turkey. [Koh, Christopher; Heller, Theo] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Glenn, Jeffrey] Stanford Univ, Sch Med, Div Gastroenterol & Hepatol, Stanford, 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1845 BP 910A EP 911A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493804206 ER PT J AU Li, Y Xia, YC Han, MF Chen, G Zhang, DK Thasler, WE Protzer, U Ning, Q AF Li, Yong Xia, Yuchen Han, Meifang Chen, Guang Zhang, Dake Thasler, Wolfgang E. Protzer, Ulrike Ning, Qin TI IFN-alpha-mediated Base Excision Repair Pathway Correlates with Antiviral Response Against Hepatitis B Virus Infection SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Li, Yong; Han, Meifang; Chen, Guang; Ning, Qin] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Wuhan, Peoples R China. [Xia, Yuchen; Protzer, Ulrike] Tech Univ Munich, Helmholtz Zentrum Munchen, Inst Virol, D-81675 Munich, Germany. [Xia, Yuchen] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. [Zhang, Dake] Chinese Acad Sci, Beijing Inst Genom, Key Lab Genom & Precis Med, Beijing, Peoples R China. [Thasler, Wolfgang E.] Univ Munich, Dept Gen Visceral Transplantat Vasc Surg Grossula, Munich, Germany. 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1864 BP 921A EP 921A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493804225 ER PT J AU Yurdaydin, C Idilman, R Kalkan, C Karakaya, F Kartal, AC Keskin, O Karatayli, E Karatayli, SC Bozdayi, AM Koh, C Heller, T Glenn, J AF Yurdaydin, Cihan Idilman, Ramazan Kalkan, Cagdas Karakaya, Fatih Kartal, Aysun Caliskan Keskin, Onur Karatayli, Ersin Karatayli, Senem C. Bozdayi, A. Mithat Koh, Christopher Heller, Theo Glenn, Jeffrey TI The Prenylation Inhibitor Lonafarnib Can Induce Post-Treatment Alt Flares With Viral Clearance In Patients With Chronic Delta Hepatitis SO HEPATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 11-15, 2016 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Yurdaydin, Cihan; Idilman, Ramazan; Kalkan, Cagdas; Karakaya, Fatih; Kartal, Aysun Caliskan; Keskin, Onur; Karatayli, Ersin; Karatayli, Senem C.; Bozdayi, A. Mithat] Ankara Univ, Sch Med, Gastroenterol Sect, Ankara, Turkey. [Koh, Christopher; Heller, Theo] NIDDK, Liver Dis Branch, Bethesda, MD USA. [Glenn, Jeffrey] Stanford Univ, Sch Med, Div Gastroenterol & Hepatol, Stanford, CA 94305 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 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 SU 1 MA 1875 BP 927A EP 927A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DY9YT UT WOS:000385493804236 ER PT J AU Haut, LH Gill, AL Kurupati, RK Bian, A Li, Y Giles-Davis, W Xiang, ZQ Zhou, XY Ertl, HCJ AF Haut, Larissa H. Gill, Amanda L. Kurupati, Raj K. Bian, Ang Li, Yan Giles-Davis, Wynetta Xiang, Zhiquan Zhou, Xiang Yang Ertl, Hildegund C. J. TI A Partial E3 Deletion in Replication-Defective Adenoviral Vectors Allows for Stable Expression of Potentially Toxic Transgene Products SO HUMAN GENE THERAPY METHODS LA English DT Article DE HIV-1; vaccine; genetic stability; immune responses ID CD8(+) T-CELLS; CHIMPANZEE ADENOVIRUS; PROTECTIVE EFFICACY; TRANSCRIPTION UNIT; NONHUMAN-PRIMATES; RHESUS MACAQUES; FUSION PROTEIN; DOUBLE-BLIND; VACCINE; HIV-1 AB Adenovirus (Ad) is used extensively for construction of viral vectors, most commonly with deletion in its E1 and/or E3 genomic regions. Previously, our attempts to insert envelope proteins (Env) of HIV-1 into such vectors based on chimpanzee-derived Ad (AdC) viruses were thwarted. Here, we describe that genetic instability of an E1- and E3-deleted AdC vector of serotype C6 expressing Env of HIV-1 can be overcome by reinsertion of E3 sequences with anti-apoptotic activities. This partial E3 deletion presumably delays premature death of HEK-293 packaging cell lines due to Env-induced cell apoptosis. The same partial E3 deletion also allows for the generation of stable glycoprotein 140 (gp140)- and gp160-expressing Ad vectors based on AdC7, a distinct AdC serotype. Env-expressing AdC vectors containing the partial E3 deletion are genetically stable upon serial cell culture passaging, produce yields comparable to those of other AdC vectors, and induce transgene product-specific antibody responses in mice. A partial E3 deletion thereby allows expansion of the repertoire of transgenes that can be expressed by Ad vectors. C1 [Haut, Larissa H.; Gill, Amanda L.; Kurupati, Raj K.; Bian, Ang; Li, Yan; Giles-Davis, Wynetta; Xiang, Zhiquan; Zhou, Xiang Yang; Ertl, Hildegund C. J.] Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA. [Gill, Amanda L.] NIAID, Clin Mol Regulat Sect, Immunoregulat Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Ertl, HCJ (reprint author), Wistar Inst Anat & Biol, Dept Immunol, 3601 Spruce St,Room 283, Philadelphia, PA 19104 USA. EM ertl@wistar.upenn.edu FU NIAID/IPCAVD [U19 AI074078] FX We wish to thank C. Cole for help with preparing the manuscript. Funding for this project was provided by the NIAID/IPCAVD U19 AI074078. NR 44 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1946-6536 EI 1946-6544 J9 HUM GENE THER METHOD JI Hum. Gene Ther. Methods PD OCT PY 2016 VL 27 IS 5 BP 187 EP 196 DI 10.1089/hgtb.2016.044 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA EA6YT UT WOS:000386775800003 PM 27604324 ER PT J AU Teratani-Ota, Y Yamamizu, K Piao, Y Sharova, L Amano, M Yu, H Schlessinger, D Ko, MSH Sharov, AA AF Teratani-Ota, Yusuke Yamamizu, Kohei Piao, Yulan Sharova, Lioudmila Amano, Misa Yu, Hong Schlessinger, David Ko, Minoru S. H. Sharov, Alexei A. TI Induction of specific neuron types by overexpression of single transcription factors SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE GABAergic neurons; Dopaminergic neurons; Cholinergic neurons; Ascl1; ESCs; Gene expression profiling; miRNA ID EMBRYONIC STEM-CELLS; DOPAMINERGIC-NEURONS; HUMAN FIBROBLASTS; IN-VIVO; CORTICOFUGAL NEURONS; PARKINSONS-DISEASE; TISSUE-SPECIFICITY; FUNCTIONAL-NEURONS; GABAERGIC NEURONS; DIRECT CONVERSION AB Specific neuronal types derived from embryonic stem cells (ESCs) can facilitate mechanistic studies and potentially aid in regenerative medicine. Existing induction methods, however, mostly rely on the effects of the combined action of multiple added growth factors, which generally tend to result in mixed populations of neurons. Here, we report that overexpression of specific transcription factors (TFs) in ESCs can rather guide the differentiation of ESCs towards specific neuron lineages. Analysis of data on gene expression changes 2 d after induction of each of 185 TFs implicated candidate TFs for further ESC differentiation studies. Induction of 23 TFs (out of 49 TFs tested) for 6 d facilitated neural differentiation of ESCs as inferred from increased proportion of cells with neural progenitor marker PSA-NCAM. We identified early activation of the Notch signaling pathway as a common feature of most potent inducers of neural differentiation. The majority of neuron-like cells generated by induction of Ascl1, Smad7, Nr2f1, Dlx2, Dlx4, Nr2f2, Barhl2, and Lhx1 were GABA-positive and expressed other markers of GABAergic neurons. In the same way, we identified Lmx1a and Nr4a2 as inducers for neurons bearing dopaminergic markers and Isl1, Fezf2, and St18 for cholinergic motor neurons. A time-course experiment with induction of Ascl1 showed early upregulation of most neural-specific messenger RNA (mRNA) and microRNAs (miRNAs). Sets of Ascl1-induced mRNAs and miRNAs were enriched in Ascl1 targets. In further studies, enrichment of cells obtained with the induction of Ascl1, Smad7, and Nr2f1 using microbeads resulted in essentially pure population of neuron-like cells with expression profiles similar to neural tissues and expressed markers of GABAergic neurons. In summary, this study indicates that induction of transcription factors is a promising approach to generate cultures that show the transcription profiles characteristic of specific neural cell types. C1 [Teratani-Ota, Yusuke; Yamamizu, Kohei; Piao, Yulan; Sharova, Lioudmila; Amano, Misa; Yu, Hong; Schlessinger, David; Sharov, Alexei A.] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. [Teratani-Ota, Yusuke] Univ Calif Davis, Dept Psychol, Ctr Neurosci, Davis, CA 95616 USA. [Yamamizu, Kohei] Kyoto Univ, Ctr iPS Cell Res & Applicat CiRA, Lab Stem Cell Differentiat, Kyoto 6068507, Japan. [Amano, Misa; Yu, Hong] Elixirgen LLC, Baltimore, MD 21205 USA. [Ko, Minoru S. H.] Keio Univ, Dept Syst Med, Sakaguchi Lab, Sch Med, Tokyo 1608582, Japan. RP Sharov, AA (reprint author), NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. EM sharoval@mail.nih.gov FU Intramural Research Program of the NIH, National Institute on Aging [Z01 AG000656-09]; Post-Baccalaureate Intramural Research Training Award; Kanae Foundation, Japan; Uehara Memorial Foundation, Japan; Naito Foundation, Japan; Japan Society for Promotion of Science (JSPS); Japan Science and Technology Agency (JST), CREST program FX This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging, project Z01 AG000656-09. Y.T-O. was funded by Post-Baccalaureate Intramural Research Training Award. K.Y. was supported by the postdoctoral fellowships from the Kanae Foundation, Japan, Uehara Memorial Foundation, Japan, Naito Foundation, Japan, and the Japan Society for Promotion of Science (JSPS). This research was also supported in part by the Japan Science and Technology Agency (JST), CREST program. The authors declare no competing financial interests. Y.T-O., K.Y., Y.P., and L.S. performed experiments; M.A. made new ES clones; H.Y. carried out vector construction for ES clones and synthetic mRNA; D.S. and M.S.H.K supervised the project and edited the manuscript; and A.A.S. performed statistical analysis and wrote the manuscript. NR 74 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-2690 EI 1543-706X J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD OCT PY 2016 VL 52 IS 9 BP 961 EP 973 DI 10.1007/s11626-016-0056-7 PG 13 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA EA5KE UT WOS:000386658200008 PM 27251161 ER PT J AU Park, YM Steck, SE Fung, TT Zhang, J Hazlett, LJ Han, K Merchant, AT AF Park, Y-M Steck, S. E. Fung, T. T. Zhang, J. Hazlett, L. J. Han, K. Merchant, A. T. TI Mediterranean diet and mortality risk in metabolically healthy obese and metabolically unhealthy obese phenotypes SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article ID NUTRITION EXAMINATION SURVEY; CORONARY-HEART-DISEASE; KOREA NATIONAL-HEALTH; CARDIOVASCULAR-DISEASE; RECOVERY BIOMARKERS; ALCOHOL-CONSUMPTION; PHYSICAL-ACTIVITY; ADIPOSE-TISSUE; US POPULATION; WEIGHT-LOSS AB BACKGROUND: The Mediterranean diet has been consistently associated with reduced mortality risk. Few prospective studies have examined whether the benefits from a Mediterranean diet are equally shared by obese individuals with varying metabolic health. OBJECTIVE: The objective of this study was to investigate the association between Mediterranean diet, metabolic phenotypes and mortality risk in a representative obese US population. METHODS: Data from 1739 adults aged 20-88 years were analyzed from participants of the National Health and Nutrition Examination Survey III, 1988-1994 followed up for deaths until 31 December 2011 in a prospective cohort analysis. Mediterranean Diet Scores (MDS) were created to assess the adherence to Mediterranean diet. Participants were classified as metabolically healthy obese (MHO) phenotype (0 or 1 metabolic abnormality) or metabolically unhealthy obese (MUO) phenotype (two or more metabolic abnormalities), based on high glucose, insulin resistance, blood pressure, triglycerides, C-reactive protein and low high-density lipoprotein cholesterol. RESULTS: The MHO phenotype (n = 598) was observed in 34.8% (s.e., 1.7%) of those who were obese (mean body mass index was 33.4 and 34.8 in MHO and MUO phenotypes, respectively). During a median follow-up of 18.5 years, there were 77 (12.9%) and 309 (27.1%) deaths in MHO and MUO individuals, respectively. In MHO individuals, the multivariable-adjusted hazard ratio (HR) of all-cause mortality in the highest tertile compared with the first tertile of MDS was 0.44 (95% confidence interval (CI), 0.26-0.75; P for trend < 0.001), after adjustment for potential confounders. A five-point (1 s.d.) increment in the adherence to MDS was associated with a 41% reduction in the risk of all-cause mortality (HR, 0.59; 95% CI, 0.37-0.94). Similar findings were obtained when we restricted our analyses to those with or without prevalent diabetes mellitus and hypertension. We did not observe mortality risk reduction in either individuals with MUO phenotype or all obese participants combined. CONCLUSIONS: Adherence to a Mediterranean dietary pattern appears to reduce mortality in the MHO phenotype, but not among the MUO phenotype in an obese population. C1 [Park, Y-M; Steck, S. E.; Zhang, J.; Hazlett, L. J.; Merchant, A. T.] Univ South Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, 915 Greene St, Columbia, SC 29208 USA. [Park, Y-M] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Fung, T. T.] Simmons Coll, Dept Nutr, Boston, MA 02115 USA. [Fung, T. T.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Han, K.] Catholic Univ Korea, Coll Med, Dept Biostat, Seoul, South Korea. RP Merchant, AT (reprint author), Univ South Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, 915 Greene St, Columbia, SC 29208 USA. EM merchant@mailbox.sc.edu OI PARK, YONG-MOON/0000-0002-5879-6879 NR 54 TC 1 Z9 1 U1 3 U2 3 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 OCT PY 2016 VL 40 IS 10 BP 1541 EP 1549 DI 10.1038/ijo.2016.114 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA EA4JZ UT WOS:000386579500011 PM 27339604 ER PT J AU Zhang, Y Ji, G Xu, M Cai, W Zhu, Q Qian, L Zhang, YE Yuan, K Liu, J Li, Q Cui, G Wang, H Zhao, Q Wu, K Fan, D Gold, MS Tian, J Tomasi, D Liu, Y Nie, Y Wang, GJ AF Zhang, Y. Ji, G. Xu, M. Cai, W. Zhu, Q. Qian, L. Zhang, Y. E. Yuan, K. Liu, J. Li, Q. Cui, G. Wang, H. Zhao, Q. Wu, K. Fan, D. Gold, M. S. Tian, J. Tomasi, D. Liu, Y. Nie, Y. Wang, G-J TI Recovery of brain structural abnormalities in morbidly obese patients after bariatric surgery SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article ID GASTRIC BYPASS-SURGERY; FOOD ADDICTION SCALE; HIGH-CALORIE FOODS; BODY-MASS INDEX; WEIGHT-LOSS; COGNITIVE CONTROL; FUTURE INCREASES; NETWORK; MRI; ACTIVATION AB BACKGROUND/OBJECTIVES: Obesity-related brain structural abnormalities have been reported extensively, and bariatric surgery (BS) is currently the most effective intervention to produce sustained weight reduction in overtly obese (OB) people. It is unknown whether BS can repair the brain circuitry abnormalities concomitantly with long-term weight loss. SUBJECTS/ METHODS: In order to investigate whether BS promotes neuroplastic structural recovery in morbidly OB patients, we quantified fractional anisotropy (FA), mean diffusivity (MD) and gray (GM) and white (WM) matter densities in 15 morbidly OB patients and in 18 normal weight (NW) individuals. OB patients were studied at baseline and also 1 month after laparoscopic sleeve gastrectomy surgery. RESULTS: Two-sample t-test between OB (baseline) and NW groups showed decreased FA values, GM/WM densities and increased MD value in brain regions associated with food intake control (that is, caudate, orbitofrontal cortex, body and genu of corpus callosum) and cognitive-emotion regulation (that is, inferior frontal gyrus, hippocampus, insula, external capsule) (P < 0.05, familywise error correction). Paired t-test in the OB group between before and after surgery showed that BS generated partial neuroplastic structural recovery in the OB group, but the differences had relative less strength and smaller volume (P < 0.001). CONCLUSIONS: This study provides the first anatomical evidence for BS-induced acute neuroplastic recovery that might in part mediate the long-term benefit of BS in weight reduction. It also highlights the importance of this line of gut-brain axis research employing the combined BS and neuroimaging model for identifying longitudinal changes in brain structure that correlated with obesity status. C1 [Zhang, Y.; Cai, W.; Zhu, Q.; Yuan, K.; Liu, J.; Tian, J.] Xidian Univ, Sch Life Sci & Technol, Ctr Brain Imaging, Xian 710071, Shaanxi, Peoples R China. [Zhang, Y.; Zhang, Y. E.; Gold, M. S.; Liu, Y.] Univ Florida, Dept Psychiat, Gainesville, FL 32611 USA. [Zhang, Y.; Zhang, Y. E.; Gold, M. S.; Liu, Y.] Univ Florida, McKnight Brain Inst, Gainesville, FL USA. [Ji, G.; Zhao, Q.; Wu, K.; Fan, D.; Nie, Y.] Fourth Mil Med Univ, Xijing Gastrointestinal Hosp, 127 Changle West Rd, Xian 710032, Shaanxi, Peoples R China. [Xu, M.; Qian, L.; Liu, Y.] Peking Univ, Dept Biomed Engn, Beijing, Peoples R China. [Zhang, Y. E.] Malcom Randall Vet Affairs Med Ctr, Gainesville, FL USA. [Li, Q.; Cui, G.] Fourth Mil Med Univ, Tangdu Hosp, Dept Radiol, Xian, Peoples R China. [Wang, H.] Fourth Mil Med Univ, Xijing Hosp, Dept Psychiat, Xian, Peoples R China. [Tian, J.] Chinese Acad Sci, Inst Automat, Beijing, Peoples R China. [Tomasi, D.; Wang, G-J] NIAAA, Lab Neuroimaging, 10 Ctr Dr,MSC1013,Bldg 10,Room B2L304, Bethesda, MD 20892 USA. RP Zhang, Y (reprint author), Xidian Univ, Sch Life Sci & Technol, Ctr Brain Imaging, Xian 710071, Shaanxi, Peoples R China.; Nie, Y (reprint author), Fourth Mil Med Univ, Xijing Gastrointestinal Hosp, 127 Changle West Rd, Xian 710032, Shaanxi, Peoples R China.; Wang, GJ (reprint author), NIAAA, Lab Neuroimaging, 10 Ctr Dr,MSC1013,Bldg 10,Room B2L304, Bethesda, MD 20892 USA. EM zhangyiuf@gmail.com; yongznie@fmmu.edu.cn; gene-jack.wang@nih.gov FU National Natural Science Foundation of China [81271549, 81470816, 61131003, 61431013, 81201081, 81227901, 81120108005, 81501543, 81371530, 81571751, 81571753]; Shaanxi Provincial Natural Science Foundation [2015JM3117]; Project for the National Key Basic Research and Development Program (973) [2011CB707700] FX This work is supported by the National Natural Science Foundation of China under Grant Nos. 81271549, 81470816, 61131003, 61431013, 81201081, 81227901, 81120108005, 81501543, 81371530, 81571751 and 81571753; the Shaanxi Provincial Natural Science Foundation under Grant No. 2015JM3117; and the Project for the National Key Basic Research and Development Program (973) under Grant No. 2011CB707700. We thank Dr Samantha Cunningham of NIAAA and Dr Jiayu Liu of Yale University for proofreading. NR 46 TC 0 Z9 0 U1 4 U2 4 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 OCT PY 2016 VL 40 IS 10 BP 1558 EP 1565 DI 10.1038/ijo.2016.98 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA EA4JZ UT WOS:000386579500013 PM 27200505 ER PT J AU Wu, J Peters, BA Dominianni, C Zhang, YL Pei, ZH Yang, LY Ma, YF Purdue, MP Jacobs, EJ Gapstur, SM Li, HL Alekseyenko, AV Hayes, RB Ahn, JY AF Wu, Jing Peters, Brandilyn A. Dominianni, Christine Zhang, Yilong Pei, Zhiheng Yang, Liying Ma, Yingfei Purdue, Mark P. Jacobs, Eric J. Gapstur, Susan M. Li, Huilin Alekseyenko, Alexander V. Hayes, Richard B. Ahn, Jiyoung TI Cigarette smoking and the oral microbiome in a large study of American adults SO ISME JOURNAL LA English DT Article ID CANCER SCREENING TRIAL; POLYMORPHONUCLEAR LEUKOCYTES; TOBACCO SMOKING; PERIODONTITIS; CESSATION; BACTERIA; SMOKERS; SALIVA; LUNG; METAANALYSIS AB Oral microbiome dysbiosis is associated with oral disease and potentially with systemic diseases; however, the determinants of these microbial imbalances are largely unknown. In a study of 1204 US adults, we assessed the relationship of cigarette smoking with the oral microbiome. 16S rRNA gene sequencing was performed on DNA from oral wash samples, sequences were clustered into operational taxonomic units (OTUs) using QIIME and metagenomic content was inferred using PICRUSt. Overall oral microbiome composition differed between current and non-current (former and never) smokers (Po0.001). Current smokers had lower relative abundance of the phylum Proteobacteria (4.6%) compared with never smokers (11.7%) (false discovery rate q= 5.2 x 10(-7)), with no difference between former and never smokers; the depletion of Proteobacteria in current smokers was also observed at class, genus and OTU levels. Taxa not belonging to Proteobacteria were also associated with smoking: the genera Capnocytophaga, Peptostreptococcus and Leptotrichia were depleted, while Atopobium and Streptococcus were enriched, in current compared with never smokers. Functional analysis from inferred metagenomes showed that bacterial genera depleted by smoking were related to carbohydrate and energy metabolism, and to xenobiotic metabolism. Our findings demonstrate that smoking alters the oral microbiome, potentially leading to shifts in functional pathways with implications for smoking-related diseases. C1 [Wu, Jing; Peters, Brandilyn A.; Dominianni, Christine; Hayes, Richard B.; Ahn, Jiyoung] NYU, Sch Med, Dept Populat Hlth, Div Epidemiol, New York, NY USA. [Wu, Jing; Pei, Zhiheng; Hayes, Richard B.; Ahn, Jiyoung] NYU, Perlmutter Canc Ctr, New York, NY USA. [Zhang, Yilong; Li, Huilin] NYU, Sch Med, Dept Populat Hlth, Div Biostat, New York, NY USA. [Pei, Zhiheng; Ma, Yingfei] NYU, Sch Med, Dept Pathol, New York, NY USA. [Pei, Zhiheng] New York Harbor Healthcare Syst, Dept Vet Affairs, New York, NY USA. [Yang, Liying] NYU, Sch Med, Dept Med, Div Translat Med, New York, NY USA. [Purdue, Mark P.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Purdue, Mark P.] Ontario Inst Canc Res, Toronto, ON, Canada. [Jacobs, Eric J.; Gapstur, Susan M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Alekseyenko, Alexander V.] Med Univ South Carolina, Biomed Informat Ctr, Charleston, SC 29425 USA. [Alekseyenko, Alexander V.] Med Univ South Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Alekseyenko, Alexander V.] Med Univ South Carolina, Dept Oral Hlth Sci, Charleston, SC 29425 USA. RP Ahn, JY (reprint author), NYU, Sch Med, Dept Populat Hlth, 650 Ist Ave,5th Floor, New York, NY 10016 USA. EM Jiyoung.Ahn@nyumc.org OI Alekseyenko, Alexander/0000-0002-5748-2085; Yang, Liying/0000-0003-1442-4915; Peters, Brandilyn/0000-0002-1534-2578; Pei, Zhiheng/0000-0001-8570-6747; Hayes, Richard/0000-0002-0918-661X FU US National Cancer Institute [R01CA159036, U01CA182370, U01CA170948-01A1, R01CA164964, R03CA159414, P30CA016087, R21CA183887]; AACR/Pancreas Cancer Action Network Career Development Award; American Cancer Society (ACS) FX Research reported in this publication was supported in part by the US National Cancer Institute under award numbers R01CA159036, U01CA182370, U01CA170948-01A1, R01CA164964, R03CA159414, P30CA016087, R21CA183887, and by AACR/Pancreas Cancer Action Network Career Development Award. ZP is a Staff Physician at the Department of Veterans Affairs New York Harbor Healthcare System. The American Cancer Society (ACS) funds the creation, maintenance and updating of the Cancer Prevention Study II cohort. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the US Department of Veterans Affairs or the United States Government. NR 55 TC 3 Z9 3 U1 17 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1751-7362 EI 1751-7370 J9 ISME J JI ISME J. PD OCT PY 2016 VL 10 IS 10 BP 2435 EP 2446 DI 10.1038/ismej.2016.37 PG 12 WC Ecology; Microbiology SC Environmental Sciences & Ecology; Microbiology GA EB0LN UT WOS:000387035400008 PM 27015003 ER PT J AU Maas, P Barrdahl, M Joshi, AD Auer, PL Gaudet, MM Milne, RL Schumacher, FR Anderson, WF Check, D Chattopadhyay, S Baglietto, L Berg, CD Chanock, SJ Cox, DG Figueroa, JD Gail, MH Graubard, BI Haiman, CA Hankinson, SE Hoover, RN Isaacs, C Kolonel, LN Le Marchand, L Lee, IM Lindstrom, S Overvad, K Romieu, I Sanchez, MJ Southey, MC Stram, DO Tumino, R VanderWeele, TJ Willett, WC Zhang, SM Buring, JE Canzian, F Gapstur, SM Henderson, BE Hunter, DJ Giles, GG Prentice, RL Ziegler, RG Kraft, P Garcia-Closas, M Chatterjee, N AF Maas, Paige Barrdahl, Myrto Joshi, Amit D. Auer, Paul L. Gaudet, Mia M. Milne, Roger L. Schumacher, Fredrick R. Anderson, William F. Check, David Chattopadhyay, Subham Baglietto, Laura Berg, Christine D. Chanock, Stephen J. Cox, David G. Figueroa, Jonine D. Gail, Mitchell H. Graubard, Barry I. Haiman, Christopher A. Hankinson, Susan E. Hoover, Robert N. Isaacs, Claudine Kolonel, Laurence N. Le Marchand, Loic Lee, I-Min Lindstrom, Sara Overvad, Kim Romieu, Isabelle Sanchez, Maria-Jose Southey, Melissa C. Stram, Daniel O. Tumino, Rosario VanderWeele, Tyler J. Willett, Walter C. Zhang, Shumin Buring, Julie E. Canzian, Federico Gapstur, Susan M. Henderson, Brian E. Hunter, David J. Giles, Graham G. Prentice, Ross L. Ziegler, Regina G. Kraft, Peter Garcia-Closas, Montse Chatterjee, Nilanjan TI Breast Cancer Risk From Modifiable and Nonmodifiable Risk Factors Among White Women in the United States SO JAMA ONCOLOGY LA English DT Article ID GENOME-WIDE ASSOCIATION; SINGLE-NUCLEOTIDE POLYMORPHISMS; GENE-ENVIRONMENT INTERACTIONS; SUSCEPTIBILITY LOCI; COHORT CONSORTIUM; MODELS; PREDICTION; INDIVIDUALS; INFORMATION; VARIANTS AB IMPORTANCE An improved model for risk stratification can be useful for guiding public health strategies of breast cancer prevention. OBJECTIVE To evaluate combined risk stratification utility of common low penetrant single nucleotide polymorphisms (SNPs) and epidemiologic risk factors. DESIGN, SETTING, AND PARTICIPANTS Using a total of 17 171 cases and 19 862 controls sampled from the Breast and Prostate Cancer Cohort Consortium (BPC3) and 5879 women participating in the 2010 National Health Interview Survey, a model for predicting absolute risk of breast cancer was developed combining information on individual level data on epidemiologic risk factors and 24 genotyped SNPs from prospective cohort studies, published estimate of odds ratios for 68 additional SNPs, population incidence rate from the National Cancer Institute-Surveillance, Epidemiology, and End Results Program cancer registry and data on risk factor distribution from nationally representative health survey. The model is used to project the distribution of absolute risk for the population of white women in the United States after adjustment for competing cause of mortality. EXPOSURES Single nucleotide polymorphisms, family history, anthropometric factors, menstrual and/ or reproductive factors, and lifestyle factors. MAIN OUTCOMES AND MEASURES Degree of stratification of absolute risk owing to nonmodifiable (SNPs, family history, height, and some components of menstrual and/ or reproductive history) and modifiable factors (body mass index [BMI; calculated as weight in kilograms divided by height in meters squared], menopausal hormone therapy [MHT], alcohol, and smoking). RESULTS The average absolute risk for a 30-year-old white woman in the United States developing invasive breast cancer by age 80 years is 11.3%. A model that includes all risk factors provided a range of average absolute risk from 4.4% to 23.5% for women in the bottom and top deciles of the risk distribution, respectively. For women who were at the lowest and highest deciles of nonmodifiable risks, the 5th and 95th percentile range of the risk distribution associated with 4 modifiable factors was 2.9% to 5.0% and 15.5% to 25.0%, respectively. For women in the highest decile of risk owing to nonmodifiable factors, those who had low BMI, did not drink or smoke, and did not use MHT had risks comparable to an average woman in the general population. CONCLUSIONS AND RELEVANCE This model for absolute risk of breast cancer including SNPs can provide stratification for the population of white women in the United States. The model can also identify subsets of the population at an elevated risk that would benefit most from risk-reduction strategies based on altering modifiable factors. The effectiveness of this model for individual risk communication needs further investigation. C1 [Maas, Paige; Anderson, William F.; Check, David; Chattopadhyay, Subham; Chanock, Stephen J.; Figueroa, Jonine D.; Gail, Mitchell H.; Graubard, Barry I.; Hoover, Robert N.; Ziegler, Regina G.; Garcia-Closas, Montse; Chatterjee, Nilanjan] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Barrdahl, Myrto] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Joshi, Amit D.; Lindstrom, Sara; Hunter, David J.; Kraft, Peter] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Program Genet Epidemiol & Stat Genet, Boston, MA USA. [Auer, Paul L.; Prentice, Ross L.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Auer, Paul L.] Univ Wisconsin, Sch Publ Hlth, Milwaukee, WI 53201 USA. [Gaudet, Mia M.; Gapstur, Susan M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Milne, Roger L.; Baglietto, Laura; Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Milne, Roger L.; Baglietto, Laura; Giles, Graham G.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia. [Schumacher, Fredrick R.; Haiman, Christopher A.; Stram, Daniel O.; Henderson, Brian E.] Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. [Berg, Christine D.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Cox, David G.] Ctr Leon Berard, INSERM, U1052, Canc Res Ctr Lyon, Lyon, France. [Cox, David G.] Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. [Hankinson, Susan E.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Dept Biostat & Epidemiol, Amherst, MA 01003 USA. [Hankinson, Susan E.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Hankinson, Susan E.; Lee, I-Min; Zhang, Shumin; Buring, Julie E.] Harvard Med Sch, Boston, MA USA. [Isaacs, Claudine] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Kolonel, Laurence N.] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA. [Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA. [Lee, I-Min; Zhang, Shumin; Buring, Julie E.] Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA. [Overvad, Kim] Aarhus Univ, Dept Publ Hlth, Aarhus, Denmark. [Romieu, Isabelle] Int Agcy Res Canc, Nutr & Metab Sect, Lyon, France. [Sanchez, Maria-Jose] Univ Granada, Hosp Univ Granada, Inst Invest Biosanitaria Ibs GRANADA, Escuela Andaluza Salud Publ, Granada, Spain. [Sanchez, Maria-Jose] CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain. [Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic, Australia. [Tumino, Rosario] Civ MP Arezzo Hosp, ASP Ragusa, Canc Registry & Histopathol Unit, Ragusa, Italy. [VanderWeele, Tyler J.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [VanderWeele, Tyler J.] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Willett, Walter C.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Canzian, Federico] German Canc Res Ctr, Heidelberg, Germany. [Giles, Graham G.] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic, Australia. [Prentice, Ross L.] Univ Washington, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. [Garcia-Closas, Montse] Inst Canc Res, Breakthrough Breast Canc Res Ctr, Div Genet & Epidemiol, London, England. [Chatterjee, Nilanjan] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, 615 N Wolfe St, Baltimore, MD 21205 USA. [Chatterjee, Nilanjan] Johns Hopkins Univ, Sch Med, Dept Oncol, 615 N Wolfe St, Baltimore, MD 21205 USA. RP Chatterjee, N (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, 615 N Wolfe St, Baltimore, MD 21205 USA. EM nilanjan@jhu.edu FU US National Institutes of Health, National Cancer Institute [U01-CA98233-07, U01-CA98710-06, U01-CA98216-06, U01-CA98758-07]; Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services; National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; Hellenic Health Association; Stavros Niarchos Foundation FX Design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication was supported by US National Institutes of Health, National Cancer Institute (cooperative agreements U01-CA98233-07 to Dr Hunter, U01-CA98710-06 to M.J.T., U01-CA98216-06 to E.R. and R.K., and U01-CA98758-07 to Dr Henderson) and Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services. The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. EPIC Greece is funded by the Hellenic Health Association and the Stavros Niarchos Foundation. NR 37 TC 6 Z9 6 U1 9 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA EI 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD OCT 1 PY 2016 VL 2 IS 10 BP 1295 EP 1302 DI 10.1001/jamaoncol.2016.1025 PG 8 WC Oncology SC Oncology GA EA3GB UT WOS:000386488600012 PM 27228256 ER PT J AU Journy, NMY Morton, LM Kleinerman, RA Bekelman, JE de Gonzalez, AB AF Journy, Neige M. Y. Morton, Lindsay M. Kleinerman, Ruth A. Bekelman, Justin E. de Gonzalez, Amy Berrington TI Second Primary Cancers After Intensity-Modulated vs 3-Dimensional Conformal Radiation Therapy for Prostate Cancer SO JAMA ONCOLOGY LA English DT Letter C1 [Journy, Neige M. Y.; Morton, Lindsay M.; Kleinerman, Ruth A.; de Gonzalez, Amy Berrington] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Room 7E556,MSC 9778,9609 Med Ctr Dr, Bethesda, MD 20892 USA. [Bekelman, Justin E.] Abramson Canc Ctr, Dept Radiat Oncol, Philadelphia, PA USA. [Bekelman, Justin E.] Univ Penn, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Bekelman, Justin E.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Journy, NMY (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Room 7E556,MSC 9778,9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM neige.journy@nih.gov NR 6 TC 0 Z9 0 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA EI 2374-2445 J9 JAMA ONCOL JI JAMA Oncol. PD OCT 1 PY 2016 VL 2 IS 10 BP 1368 EP 1370 DI 10.1001/jamaoncol.2016.1368 PG 3 WC Oncology SC Oncology GA EA3GB UT WOS:000386488600024 PM 27415446 ER PT J AU Quinn, GE Ying, GS Repka, MX Siatkowski, RM Hoffman, R Mills, MD Morrison, D Daniel, E Baumritter, A Hildebrand, PL Schron, EB Ells, AL Wade, K Kemper, AR AF Quinn, Graham E. Ying, Gui-shuang Repka, Michael X. Siatkowski, R. Michael Hoffman, Robert Mills, Monte D. Morrison, David Daniel, Ebenezer Baumritter, Agnieshka Hildebrand, P. Lloyd Schron, Eleanor B. Ells, Anna L. Wade, Kelly Kemper, Alex R. TI Timely implementation of a retinopathy of prematurity telemedicine system SO JOURNAL OF AAPOS LA English DT Article ID ACUTE-PHASE RETINOPATHY; INFANTS; CARE; ROP AB PURPOSE To examine the feasibility of a retinopathy of prematurity (ROP) telemedicine evaluation system of providing timely feedback to a neonatal intensive care unit (NICU) with at-risk premature infants. METHODS This was a prospective observational study of premature infants with birth weights of <1251 g in five NICUs in the United States. Infants scheduled for clinically indicated ROP evaluations underwent indirect ophthalmoscopic examinations and digital imaging on the same day. Imaging was performed by nonphysician retinal imagers. Times required were determined from obtaining digital images of both eyes to submission via web-based system to a secure server for grading by trained readers at a central reading center to sending back grading results to the clinical center. RESULTS A total of 1,642 image sets of eyes of 292 infants were obtained, from 823 imaging sessions. The mean turnaround time from submission of image sets of both eyes to return of the grading results to the clinical center was 10.1 +/- 11.3 hours (standard deviation), with a median of 12.0 hours (1st quartile, 0.9 hours; 3rd quartile, 16 hours). Overall, 95.5% of gradings (95% CI, 93.9%-96.7%) were returned within 24 hours. Subgroup analyses found, for image sets submitted to the reading center before 2 p.m. Eastern Standard Time, median time to report was 1.7 hours (1st quartile, 0.7 hours; 3rd quartile, 15.5 hours) compared with those submitted after 2pm (median, 14.1 hours; 1st quartile, 11.2, hours; 3rd quartile, 16.3 hours). CONCLUSIONS An ROP telemedicine approach can provide timely feedback to the NICU regarding the detection of potentially serious ROP and thus referral to an ophthalmologist for examination and consideration of treatment. C1 [Quinn, Graham E.; Ying, Gui-shuang; Mills, Monte D.; Daniel, Ebenezer; Wade, Kelly] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA. [Quinn, Graham E.; Mills, Monte D.; Baumritter, Agnieshka; Wade, Kelly] Childrens Hosp Philadelphia, Div Pediat Ophthalmol, Philadelphia, PA 19104 USA. [Repka, Michael X.; Hildebrand, P. Lloyd] Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA. [Siatkowski, R. Michael] Univ Oklahoma, Dean McGee Eye Inst, Oklahoma City, OK USA. [Hoffman, Robert] Univ Utah, Dept Ophthalmol, Salt Lake City, UT USA. [Morrison, David] Vanderbilt Univ, Dept Ophthalmol, 221 Kirkland Hall, Nashville, TN 37235 USA. [Schron, Eleanor B.] NEI, Bethesda, MD 20892 USA. [Ells, Anna L.] Univ Calgary, Dept Ophthalmol, Calgary, AB T2N 1N4, Canada. [Kemper, Alex R.] Duke Univ, Dept Pediat, Sch Med, Durham, NC 27706 USA. RP Quinn, GE (reprint author), Childrens Hosp Philadelphia, Div Ophthalmol, Wood Ctr, 1st Floor, Philadelphia, PA 19104 USA. EM quinn@email.chop.edu FU National Eye Institute of the National Institutes of Health, Department of Health and Human Services [U10 EY017014] FX Funded by National Eye Institute of the National Institutes of Health, Department of Health and Human Services. U10 EY017014. NR 13 TC 0 Z9 0 U1 2 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-8531 EI 1528-3933 J9 J AAPOS JI J. AAPOS PD OCT PY 2016 VL 20 IS 5 BP 425 EP 430 DI 10.1016/j.jaapos.2016.06.007 PG 6 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA EA5FL UT WOS:000386644700010 PM 27651231 ER PT J AU Revell, AD Wang, DC Wood, R Morrow, C Tempelman, H Hamers, RL Reiss, P van Sighem, AI Nelson, M Montaner, JSG Lane, HC Larder, BA AF Revell, Andrew D. Wang, Dechao Wood, Robin Morrow, Carl Tempelman, Hugo Hamers, Raph L. Reiss, Peter van Sighem, Ard I. Nelson, Mark Montaner, Julio S. G. Lane, H. Clifford Larder, Brendan A. CA RDI Data Study Grp TI An update to the HIV-TRePS system: the development and evaluation of new global and local computational models to predict HIV treatment outcomes, with or without a genotype SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article ID RESOURCE-LIMITED SETTINGS; ANTIRETROVIRAL THERAPY; GUIDELINES; RESISTANCE; ADULTS AB Optimizing antiretroviral drug combination on an individual basis in resource-limited settings is challenging because of the limited availability of drugs and genotypic resistance testing. Here, we describe our latest computational models to predict treatment responses, with or without a genotype, and compare the potential utility of global and local models as a treatment tool for South Africa. Global random forest models were trained to predict the probability of virological response to therapy following virological failure using 29aEuroS574 treatment change episodes (TCEs) without a genotype, 3179 of which were from South Africa and were used to develop local models. In addition, 15aEuroS130 TCEs including genotypes were used to develop another set of models. The 'no-genotype' models were tested with an independent global test set (naEuroS=aEuroS1700) plus a subset from South Africa (naEuroS=aEuroS222). The genotype models were tested with 750 independent cases. The global no-genotype models achieved area under the receiver-operating characteristic curve (AUC) values of 0.82 and 0.79 with the global and South African tests sets, respectively, and the South African models achieved AUCs of 0.70 and 0.79. The genotype models achieved an AUC of 0.84. The global no-genotype models identified more alternative, locally available regimens that were predicted to be effective for cases that failed their new regimen in the South African clinics than the local models. Both sets of models were significantly more accurate predictors of outcomes than genotyping with rules-based interpretation. These latest global models predict treatment responses accurately even without a genotype, out-performed the local South African models and have the potential to help optimize therapy, particularly in resource-limited settings. C1 [Revell, Andrew D.; Wang, Dechao; Larder, Brendan A.] HIV Resistance Response Database Initiat RDI, London, England. [Wood, Robin; Morrow, Carl] Univ Cape Town, Desmond Tutu HIV Ctr, Cape Town, South Africa. [Tempelman, Hugo] Ndlovu Care Grp, Elandsdoorn, South Africa. [Hamers, Raph L.; Reiss, Peter] Univ Amsterdam, Amsterdam Inst Global Hlth & Dev, Acad Med Ctr, Dept Internal Med, Amsterdam, Netherlands. [Hamers, Raph L.; Reiss, Peter] Univ Amsterdam, Amsterdam Inst Global Hlth & Dev, Acad Med Ctr, Dept Global Hlth, Amsterdam, Netherlands. [Reiss, Peter; van Sighem, Ard I.] Stichting HIV Monitoring, Amsterdam, Netherlands. [Nelson, Mark] Chelsea & Westminster Hosp, London, England. [Montaner, Julio S. G.] BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada. [Lane, H. Clifford] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Revell, AD (reprint author), HIV Resistance Response Database Initiat RDI, London, England. EM andrewrevell@hivrdi.org FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; National Institute of Allergy and Infectious Diseases 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. This research was supported by the National Institute of Allergy and Infectious Diseases. NR 14 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2016 VL 71 IS 10 BP 2928 EP 2937 DI 10.1093/jac/dkw217 PG 10 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA EA2VO UT WOS:000386453900030 PM 27330070 ER PT J AU Aresh, W Liu, Y Sine, J Thayer, D Puri, A Huang, YK Wang, Y Nieh, MP AF Aresh, Wafa Liu, Ying Sine, Jessica Thayer, Derek Puri, Anu Huang, Yike Wang, Yong Nieh, Mu-Ping TI The Morphology of Self-Assembled Lipid-Based Nanoparticles Affects Their Uptake by Cancer Cells SO JOURNAL OF BIOMEDICAL NANOTECHNOLOGY LA English DT Article DE Cancer Cellular Internalization; Spontaneous Formation; Morphology-Targeting; Bicelles; Vesicles; SANS ID FORMED UNILAMELLAR VESICLES; CELLULAR UPTAKE; ENGINEERED NANOPARTICLES; MAMMALIAN-CELLS; DRUG-DELIVERY; SIZE; SHAPE; LIPOSOMES; NANODISCS; INTERNALIZATION AB The morphology of nanoparticles (NPs) has been presumed to play an important role in cellular uptake and in vivo stability. This report experimentally demonstrates such dependence by using two types of uniform-sized self-assembled lipid-based NPs, namely nanodiscs and nanovesicles, composed of identical lipid composition. The morphology is characterized by small angle neutron scattering, dynamic light scattering and transmission electron microscopy. Both NPs have similar bio-stability in serum and cellular cytotoxicity. However, cellular uptake of the nanodiscs at 37 degrees C is consistently and significantly higher than that of the vesicles according to the uptake results of several human cancer cell lines, i.e., CCRF-CEM, KB, and OVCAR-8, indicating a strong morphological dependence of cellular internalization. Further studies on such morphological dependence using CCRF-CEM reveals that vesicles only use Clathrin-and caveolae-mediated endocytic pathways, while nanodiscs also take the additional routes of macropinocytosis and microtubule-mediated endocytosis. C1 [Aresh, Wafa; Nieh, Mu-Ping] Univ Connecticut, Dept Biomed Engn, Storrs, CT 06269 USA. [Liu, Ying; Nieh, Mu-Ping] Univ Connecticut, Dept Chem & Biomol Engn, Storrs, CT 06269 USA. [Sine, Jessica; Thayer, Derek; Puri, Anu] NCI, Basic Res Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. [Huang, Yike; Wang, Yong] Penn State Univ, Dept Biomed Engn, University Pk, PA 16802 USA. [Nieh, Mu-Ping] Univ Connecticut, Inst Mat Sci, Polymer Program, Storrs, CT 06269 USA. RP Nieh, MP (reprint author), Univ Connecticut, Dept Biomed Engn, Storrs, CT 06269 USA.; Nieh, MP (reprint author), Univ Connecticut, Dept Chem & Biomol Engn, Storrs, CT 06269 USA.; Nieh, MP (reprint author), Univ Connecticut, Inst Mat Sci, Polymer Program, Storrs, CT 06269 USA. EM mu-ping.nieh@uconn.edu FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; [NSF-CMMI 1131587] FX Mu-Ping Nieh, Yong Wang, Ying Liu, and Yike Huang would like to acknowledge the financial support by NSF-CMMI 1131587 and the assistance from the staff and scientist at the Spallation Neutron Source at the Oak Ridge National Laboratory. This research was also supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. We would like to thank Mr. Patrick Hall and Mr. Joseph Bergman for their assistance in the stability of the nanoparticles. We also thank Dr. Carol Norris for the training and her assistance in the use of Flow Cytometry/Confocal Microscope at the UConn Biotechnology-Bioservice Center as well as Dr. William Heller for his help with the experiment on EQ-SANS. NR 42 TC 0 Z9 0 U1 8 U2 8 PU AMER SCIENTIFIC PUBLISHERS PI VALENCIA PA 26650 THE OLD RD, STE 208, VALENCIA, CA 91381-0751 USA SN 1550-7033 EI 1550-7041 J9 J BIOMED NANOTECHNOL JI J. Biomed. Nanotechnol. PD OCT PY 2016 VL 12 IS 10 BP 1852 EP 1863 DI 10.1166/jbn.2016.2292 PG 12 WC Nanoscience & Nanotechnology; Materials Science, Biomaterials SC Science & Technology - Other Topics; Materials Science GA EA3FN UT WOS:000386486800002 ER PT J AU Ostrom, QT Gittleman, H Kruchko, C Louis, DN Brat, DJ Gilbert, MR Petkov, VI Barnholtz-Sloan, JS AF Ostrom, Quinn T. Gittleman, Haley Kruchko, Carol Louis, David N. Brat, Daniel J. Gilbert, Mark R. Petkov, Valentina I. Barnholtz-Sloan, Jill S. TI Completeness of required site-specific factors for brain and CNS tumors in the Surveillance, Epidemiology and End Results (SEER) 18 database (2004-2012, varying) SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE WHO grade; Brain tumors; Cancer registration; MGMT methylation; 1p/19q codeletion ID MGMT PROMOTER METHYLATION; CENTRAL-NERVOUS-SYSTEM; DNA-REPAIR GENE; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; ANAPLASTIC OLIGODENDROGLIOMAS; GRADE GLIOMAS; TEMOZOLOMIDE; MUTATIONS; CLASSIFICATION; TRIAL AB Cancer registries are an important source of population-level information on brain tumor incidence and survival. Surveillance, Epidemiology, and End Results (SEER) registries currently collect data on specific required factors related to brain tumors as defined by the American Joint Commission on Cancer, including World Health Organization (WHO) grade, MGMT methylation and 1p/19q codeletion status. We assessed 'completeness', defined as having valid values over the time periods that they have been collected, overall, by year, histology, and registry. Data were obtained through a SEER custom data request for four factors related to brain tumors for the years 2004-2012 (3/4 factors were collected only from 2010 to 2012). SEER*Stat was used to generate frequencies of 'completeness' for each factor overall, and by year, histology and registry. The four factors varied in completeness, but increased over time. WHO grade has been collected the longest, and showed significant increases in completeness. Completeness of MGMT and 1p/19q codeletion was highest for glioma subtypes for which testing is recommended by clinical practice guidelines. Completeness of all factors varied by histology and cancer registry. Overall, several of the factors had high completeness, and all increased in completeness over time. With increasing focus on 'precision medicine' and the incorporation of molecular parameters into the 2016 WHO CNS tumor classification, it is critical that the data are complete, and factors collected at the population level are fully integrated into cancer reporting. It is critical that cancer registries continue to collect established and emerging prognostic and predictive factors. C1 [Ostrom, Quinn T.; Gittleman, Haley; Barnholtz-Sloan, Jill S.] Case Western Reserve Univ, Case Comprehens Canc Ctr, Sch Med, 11100 Euclid Ave,Wearn 152, Cleveland, OH 44106 USA. [Ostrom, Quinn T.; Gittleman, Haley; Kruchko, Carol; Barnholtz-Sloan, Jill S.] CBTRUS, Hinsdale, IL 60521 USA. [Louis, David N.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. [Brat, Daniel J.] Emory Univ, Dept Pathol & Lab Med, Winship Canc Inst, Atlanta, GA 30322 USA. [Gilbert, Mark R.] NIH, Neurooncol Branch, Bldg 10, Bethesda, MD 20892 USA. [Petkov, Valentina I.] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Barnholtz-Sloan, JS (reprint author), Case Western Reserve Univ, Case Comprehens Canc Ctr, Sch Med, 11100 Euclid Ave,Wearn 152, Cleveland, OH 44106 USA.; Barnholtz-Sloan, JS (reprint author), CBTRUS, Hinsdale, IL 60521 USA. EM jsb42@case.edu FU National Cancer Institute Case Comprehensive Cancer Center [P30CA043703]; CBTRUS database: the Centers for Disease Control and Prevention (CDC) [5U58DP00383]; Sontag Foundation, Genentech, Novocure, Inc; Celldex Therapeutics, Inc; AbbVie, Inc; Musella Foundation; Voices Against Brain Cancer, Elekta FX QTO, HG, and JSB-S were supported by the National Cancer Institute Case Comprehensive Cancer Center Support Grant (P30CA043703). CBTRUS is honored to be included among the research grant recipients of the following organizations, which have contributed to the maintenance of the CBTRUS database: the Centers for Disease Control and Prevention (CDC) under Agreement 5U58DP00383, the Sontag Foundation, Genentech, Novocure, Inc., Celldex Therapeutics, Inc., AbbVie, Inc., along with the Musella Foundation, Voices Against Brain Cancer, Elekta, the Zelda Dorin Memorial Fund, as well as private and in kind donations. NR 42 TC 0 Z9 0 U1 3 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD OCT PY 2016 VL 130 IS 1 BP 31 EP 42 DI 10.1007/s11060-016-2217-7 PG 12 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA EA4FH UT WOS:000386565200004 PM 27418206 ER PT J AU Nesvick, CL Zhang, C Edwards, NA Montgomery, BK Lee, M Yang, CZ Wang, HR Zhu, DW Heiss, JD Merrill, MJ Ray-Chaudhury, A Zhuang, ZP AF Nesvick, Cody L. Zhang, Chao Edwards, Nancy A. Montgomery, Blake K. Lee, Michaela Yang, Chunzhang Wang, Herui Zhu, Dongwang Heiss, John D. Merrill, Marsha J. Ray-Chaudhury, Abhik Zhuang, Zhengping TI ZEB1 expression is increased in IDH1-mutant lower-grade gliomas SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE IDH; Lower-grade glioma; Epithelial-mesenchymal transition; ZEB1 ID EPITHELIAL-MESENCHYMAL TRANSITION; INTEGRATED GENOMIC ANALYSIS; GENE-EXPRESSION; GLIOBLASTOMA-MULTIFORME; TUMOR INITIATION; STEM-CELLS; MUTATIONS; INVASION; IDH1; TRANSCRIPTION AB Transcription factors that induce epithelial-mesenchymal transition (EMT) promote invasion, chemoresistance and a stem-cell phenotype in epithelial tumors, but their roles in central nervous system tumors are not well-understood. We hypothesized these transcription factors have a functional impact in grades II-III gliomas. Using the National Cancer Institute (NCI) Repository for Molecular Brain Neoplasia Data (REMBRANDT) and the Cancer Genome Atlas (TCGA) Lower-Grade Glioma (LGG) data, we determined the impact of EMT-promoting transcription factors (EMT-TFs) on overall survival in grades II-III gliomas, compared their expression across common genetic subtypes and subsequently validated these findings in a set of 31 tumors using quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry. Increased expression of the gene coding for the transcriptional repressor Zinc Finger E box-binding Homeobox 1 (ZEB1) was associated with a significant increase in overall survival (OS) on Kaplan-Meier analysis. Genetic subtype analysis revealed that ZEB1 expression was relatively increased in IDH1/2-mutant gliomas, and IDH1/2-mutant gliomas expressed significantly lower levels of many ZEB1 transcriptional targets. Similarly, IDH1/2-mutant tumors expressed significantly higher levels of targets of microRNA 200C (MIR200C), a key regulator of ZEB1. In a validation study, ZEB1 mRNA was significantly increased in IDH1-mutant grades II-III gliomas, and ZEB1 protein expression was more pronounced in these tumors. Our findings demonstrate a novel relationship between IDH1/2 mutations and expression of ZEB1 and its transcriptional targets. Therapy targeting ZEB1-associated pathways may represent a novel therapeutic avenue for this class of tumors. C1 [Nesvick, Cody L.; Zhang, Chao; Edwards, Nancy A.; Montgomery, Blake K.; Lee, Michaela; Yang, Chunzhang; Wang, Herui; Zhu, Dongwang; Heiss, John D.; Merrill, Marsha J.; Ray-Chaudhury, Abhik; Zhuang, Zhengping] NINDS, Surg Neurol Branch, 9000 Rockville Pike,Bldg 10 Room 3D17, Bethesda, MD 20892 USA. [Nesvick, Cody L.] Mayo Clin, Dept Neurol Surg, 200 1st St SW, Rochester, MN 55905 USA. [Montgomery, Blake K.] Stanford Univ, Dept Orthopaed Surg, 450 Broadway St,Pavil C,4th Floor, Redwood City, CA 94063 USA. [Lee, Michaela] George Washington Univ, Dept Neurol Surg, 2150 Penn Ave NW,Suite 7-420, Washington, DC 20037 USA. [Yang, Chunzhang] NCI, Neurooncol Branch, Bldg 37,Room 1142E, Bethesda, MD 20892 USA. RP Nesvick, CL; Zhuang, ZP (reprint author), NINDS, Surg Neurol Branch, 9000 Rockville Pike,Bldg 10 Room 3D17, Bethesda, MD 20892 USA.; Nesvick, CL (reprint author), Mayo Clin, Dept Neurol Surg, 200 1st St SW, Rochester, MN 55905 USA. EM Cody.Nesvick@gmail.com; ZhuangP@ninds.nih.gov FU Intramural Research Program at the National Institute of Neurological Disorders and Stroke; National Institutes of Health Medical Research Scholars Program FX This research was supported by the Intramural Research Program at the National Institute of Neurological Disorders and Stroke and the National Institutes of Health Medical Research Scholars Program. NR 56 TC 1 Z9 1 U1 3 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD OCT PY 2016 VL 130 IS 1 BP 111 EP 122 DI 10.1007/s11060-016-2240-8 PG 12 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA EA4FH UT WOS:000386565200012 PM 27568035 ER PT J AU Jacobson, KA Civan, MM AF Jacobson, Kenneth A. Civan, Mortimer M. TI Ocular Purine Receptors as Drug Targets in the Eye SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Review DE adenosine receptor; P2Y receptor; P2X receptor; ATP ID RETINAL GANGLION-CELLS; DIQUAFOSOL OPHTHALMIC SOLUTION; A(3) ADENOSINE RECEPTOR; MOUSE INTRAOCULAR-PRESSURE; TRAUMATIC OPTIC NEUROPATHY; TRABECULAR MESHWORK CELLS; AQUEOUS-HUMOR; DRY-EYE; A(2A) RECEPTOR; GLAUCOMA TREATMENT AB Agonists and antagonists of various subtypes of G protein coupled adenosine receptors (ARs), P2Y receptors (P2YRs), and ATP-gated P2X receptor ion channels (P2XRs) are under consideration as agents for the treatment of ocular diseases, including glaucoma and dry eye. Numerous nucleoside and nonnucleoside modulators of the receptors are available as research tools and potential therapeutic molecules. Three of the 4 subtypes of ARs have been exploited with clinical candidate molecules for treatment of the eye: A(1), A(2A), and A(3). An A(1)AR agonist is in clinical trials for glaucoma, A(2A)AR reduces neuroinflammation, A(3)AR protects retinal ganglion cells from apoptosis, and both A(3)AR agonists and antagonists had been reported to lower intraocular pressure (IOP). Extracellular concentrations of endogenous nucleotides, including dinucleoside polyphosphates, are increased in pathological states, activating P2Y and P2XRs throughout the eye. P2YR agonists, including P2Y(2) and P2Y(6), lower IOP. Antagonists of the P2X7R prevent the ATP-induced neuronal apoptosis in the retina. Thus, modulators of the purinome in the eye might be a source of new therapies for ocular diseases. C1 [Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Civan, Mortimer M.] Univ Penn, Dept Physiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Civan, Mortimer M.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM kennethj@helix.nih.gov FU NIDDK, NIH Intramural Research Program FX K.A.J. thanks the NIDDK, NIH Intramural Research Program for support. NR 123 TC 0 Z9 0 U1 4 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1080-7683 EI 1557-7732 J9 J OCUL PHARMACOL TH JI J. Ocular Pharmacol. Ther. PD OCT PY 2016 VL 32 IS 8 SI SI BP 534 EP 547 DI 10.1089/jop.2016.0090 PG 14 WC Ophthalmology; Pharmacology & Pharmacy SC Ophthalmology; Pharmacology & Pharmacy GA EA4NJ UT WOS:000386589200011 PM 27574786 ER PT J AU Louis, GMB Backonja, U Schliep, KC Sun, LP Peterson, CM Chen, Z AF Louis, Germaine M. Buck Backonja, Uba Schliep, Karen C. Sun, Liping Peterson, C. Matthew Chen, Zhen TI Women's Reproductive History Before the Diagnosis of Incident Endometriosis SO JOURNAL OF WOMENS HEALTH LA English DT Article DE endometriosis; epidemiology; fertility ID PREDICTIVE-VALUE; INFERTILE WOMEN; BODY-SIZE; PREGNANCY; POPULATION; RISK; RECURRENCE; CLASSIFICATION; ASSOCIATION; PERFORMANCE AB Background: Endometriosis is a gynecologic disease reported to be associated with infertility and, possibly, adverse pregnancy outcomes. While considerable research focuses on pregnancy outcomes following diagnosis and/or treatment, few data actually describe women's reproductive history before diagnosis for a more complete understanding of endometriosis and reproduction. Materials and Methods: The study sample comprised 473 women (aged 18-44 years) undergoing laparoscopies or laparotomies, irrespective of surgical indication at 14 clinical sites, during the period 2007-2009. Upon enrollment and before surgery, women were queried about pregnancy intentions and the time required to become pregnant for planned pregnancies. Endometriosis was defined as surgically visualized disease. Using discrete time survival analysis, we estimated fecundability odds ratios (FORs) and 95% confidence intervals (CIs) to assess time to pregnancy (TTP) after adjusting for potential confounders (age, body composition, cigarette smoking, site). Generalized estimating equations accounted for multiple pregnancy attempts per woman. FORs <1.0 denote a longer TTP or diminished fecundity. Results: Approximately 66% and 69% of women with and without endometriosis, respectively, reported having a planned pregnancy before surgery, respectively. After adjustment, an endometriosis diagnosis was associated with approximate to 29% reduction in fecundity or a longer TTP across all pregnancy-trying attempts (adjusted FOR=0.71; 95% CI 0.46-1.10). While FORs were consistently <1.0, irrespective of endometriosis staging, CIs included 1. Conclusions: Women with endometriosis had a longer TTP than unaffected women, irrespective of disease severity, although the findings did not achieve significance. Prior reproductive history may be informative for predicting fecundity and pregnancy outcomes following diagnosis/treatment. C1 [Louis, Germaine M. Buck; Backonja, Uba] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth, Rockville, MD USA. [Backonja, Uba] Univ Washington, Sch Med, Dept Biomed Informat & Med Educ, Div Biomed & Hlth Informat, Seattle, WA USA. [Schliep, Karen C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth, Rockville, MD USA. [Schliep, Karen C.] Univ Utah, Sch Med, Dept Family & Prevent Med, Div Publ Hlth, Salt Lake City, UT 84112 USA. [Sun, Liping] Glotech Corp, Rockville, MD USA. [Peterson, C. Matthew] Univ Utah, Sch Med, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Salt Lake City, UT 84132 USA. [Chen, Zhen] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth, Rockville, MD USA. RP Louis, GMB (reprint author), 6710B Rockledge Blvd, Rockville, MD 20852 USA. EM louisg@mail.nih.gov OI Buck Louis, Germaine/0000-0002-1774-4490 FU Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development [NO1-DK-6-3428, NO1-DK-6-3427, 10001406-02]; National Institutes of Health, National Library of Medicine (NLM) Biomedical and Health Informatics Training Program at the University of Washington [T15LM007442] FX This research was supported by the Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development (contracts NO1-DK-6-3428; NO1-DK-6-3427; 10001406-02). Dr. U.B. was supported as a predoctoral fellow by the National Institute for Nursing Research's Graduate Partnership Program during the course of this research and is now supported, in part, by the National Institutes of Health, National Library of Medicine (NLM) Biomedical and Health Informatics Training Program at the University of Washington (Grant Nr. T15LM007442). NR 52 TC 0 Z9 0 U1 3 U2 3 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 OCT PY 2016 VL 25 IS 10 BP 1021 EP 1029 DI 10.1089/jwh.2015.5712 PG 9 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 EA3BH UT WOS:000386472300008 ER PT J AU Lerin, C Goldfine, AB Boes, T Liu, M Kasif, S Dreyfuss, JM De Sousa-Coelho, AL Daher, G Manoli, I Sysol, JR Isganaitis, E Jessen, N Goodyear, LJ Beebe, K Gall, W Venditti, CP Patti, ME AF Lerin, Carles Goldfine, Allison B. Boes, Tanner Liu, Manway Kasif, Simon Dreyfuss, Jonathan M. De Sousa-Coelho, Ana Luisa Daher, Grace Manoli, Irini Sysol, Justin R. Isganaitis, Elvira Jessen, Niels Goodyear, Laurie J. Beebe, Kirk Gall, Walt Venditti, Charles P. Patti, Mary-Elizabeth TI Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism SO MOLECULAR METABOLISM LA English DT Article DE Insulin sensitivity; BCAA; Fatty acid oxidation; TCA cycle ID TYPE-2 DIABETES-MELLITUS; VISCERAL ADIPOSE-TISSUE; CIRCULATING BCAA LEVELS; INSULIN-RESISTANCE; SKELETAL-MUSCLE; METHYLMALONIC ACIDEMIA; GENE-EXPRESSION; ENZYME-ACTIVITY; WEIGHT-LOSS; OBESITY AB Objective: Plasma levels of branched-chain amino acids (BCAA) are consistently elevated in obesity and type 2 diabetes (T2D) and can also prospectively predict T2D. However, the role of BCAA in the pathogenesis of insulin resistance and T2D remains unclear. Methods: To identify pathways related to insulin resistance, we performed comprehensive gene expression and metabolomics analyses in skeletal muscle from 41 humans with normal glucose tolerance and 11 with T2D across a range of insulin sensitivity (SI, 0.49 to 14.28). We studied both cultured cells and mice heterozygous for the BCAA enzyme methylmalonyl-CoA mutase (Mut) and assessed the effects of altered BCAA flux on lipid and glucose homeostasis. Results: Our data demonstrate perturbed BCAA metabolism and fatty acid oxidation in muscle from insulin resistant humans. Experimental alterations in BCAA flux in cultured cells similarly modulate fatty acid oxidation. Mut heterozygosity in mice alters muscle lipid metabolism in vivo, resulting in increased muscle triglyceride accumulation, increased plasma glucose, hyperinsulinemia, and increased body weight after high-fat feeding. Conclusions: Our data indicate that impaired muscle BCAA catabolism may contribute to the development of insulin resistance by perturbing both amino acid and fatty acid metabolism and suggest that targeting BCAA metabolism may hold promise for prevention or treatment of T2D. (C) 2016 The Authors. Published by Elsevier GmbH. C1 [Lerin, Carles; Goldfine, Allison B.; Boes, Tanner; Dreyfuss, Jonathan M.; De Sousa-Coelho, Ana Luisa; Daher, Grace; Isganaitis, Elvira; Jessen, Niels; Goodyear, Laurie J.; Patti, Mary-Elizabeth] Joslin Diabet Ctr, Res Div, Boston, MA 02215 USA. [Lerin, Carles; Goldfine, Allison B.; De Sousa-Coelho, Ana Luisa; Isganaitis, Elvira; Patti, Mary-Elizabeth] Harvard Med Sch, Boston, MA 02215 USA. [Lerin, Carles] Hosp St Joan Deu, Inst Recerca Pediat, Endocrinol Dept, Barcelona 08950, Spain. [Liu, Manway; Kasif, Simon; Dreyfuss, Jonathan M.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Manoli, Irini; Sysol, Justin R.; Venditti, Charles P.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Beebe, Kirk; Gall, Walt] Metabolon Inc, Durham, NC 27723 USA. [Gall, Walt] Saffron Technol, Cary, NC 27513 USA. RP Patti, ME (reprint author), Joslin Diabet Ctr, One Joslin Pl, Boston, MA 02215 USA.; Lerin, C (reprint author), Hosp St Joan Deu, Inst Recerca Pediat, Barcelona 08950, Spain. EM clerin@fsjd.org; mary.elizabeth.patti@joslin.harvard.edu OI Jessen, Niels/0000-0001-5613-7274 FU NICHD NIH HHS [K99 HD064793]; NIDDK NIH HHS [K23 DK002795, P30 DK036836, R01 DK101043]; NLM NIH HHS [U54 LM008748] NR 64 TC 0 Z9 0 U1 10 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2212-8778 J9 MOL METAB JI Mol. Metab. PD OCT PY 2016 VL 5 IS 10 BP 926 EP 936 DI 10.1016/j.molmet.2016.08.001 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EA8KC UT WOS:000386882700012 PM 27689005 ER PT J AU Bachis, A Wenzel, E Boelk, A Becker, J Mocchetti, I AF Bachis, Alessia Wenzel, Erin Boelk, Allyssia Becker, Jodi Mocchetti, Italo TI The neurotrophin receptor p75 mediates gp120-induced loss of synaptic spines in aging mice SO NEUROBIOLOGY OF AGING LA English DT Article DE Aging; Hippocampus; HIV; p75NTR; proBDNF; TrkB ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; ENVELOPE PROTEIN GP120; LONG-TERM POTENTIATION; ANTIRETROVIRAL THERAPY; HIPPOCAMPAL-NEURONS; ALZHEIMERS-DISEASE; HIV-1 ENCEPHALITIS; AXONAL-TRANSPORT; DENDRITIC GROWTH AB Human immunodeficiency virus 1 and its envelope protein gp120 reduce synaptodendritic complexity. However, the mechanisms contributing to this pathological feature are still not understood. The proneurotrophin brain-derived neurotrophic factor promotes synaptic simplification through the activation of the p75 neurotrophin receptor (p75NTR). Here, we have used gp120 transgenic (gp120tg) mice to investigate whether p75NTR has a role in gp120-mediated neurotoxicity. Old (similar to 10 months) gp120tg mice exhibited an increase in proneurotrophin brain-derived neurotrophic factor levels in the hippocampus as well as a decrease in the number of dendritic spines when compared to age-matched wild type. These effects were not observed in 3-or 6-month-old mice. To test if the reduction in spine density and morphology is caused by the activation of p75NTR, we crossed gp120tg mice with p75NTR null mice. We found that deletion of only 1 copy of the p75NTR gene in gp120tg mice is sufficient to normalize the number of hippocampal spines, strongly suggesting that the neurotoxic effect of gp120 is mediated by p75NTR. These data indicate that p75NTR antagonists could provide an adjunct therapy against synaptic simplification caused by human immunodeficiency virus 1. (C) 2016 Elsevier Inc. All rights reserved. C1 [Bachis, Alessia; Wenzel, Erin; Boelk, Allyssia; Mocchetti, Italo] Georgetown Univ, Med Ctr, Dept Neurosci, Lab Preclin Neurobiol, Washington, DC 20007 USA. [Wenzel, Erin] Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20007 USA. [Becker, Jodi] NCI, Ctr Canc Res, Frederick, MD 21701 USA. RP Mocchetti, I (reprint author), Georgetown Univ, Med Ctr, EP09 New Res Bldg,3970 Reservoir Rd NW, Washington, DC 20057 USA. EM moccheti@georgetown.edu FU HHS [NS079172, NS074916] FX This work was supported by HHS grants NS079172 and NS074916. Special thanks to Dr. Eliezer Masliah (University of California San Diego, San Diego, CA) for the breading pairs of gp120tg mice, to Dr. Bruce Carter (Vanderbilt University, Nashville, TE) for the gift of the p75NTR antibody, and Lino Tessarollo (NCI-Frederick, MD) for discussions and advice with the animal studies. The authors are grateful to the National NeuroAIDS Tissue Consortium for providing human brain tissues. NR 57 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD OCT PY 2016 VL 46 BP 160 EP 168 DI 10.1016/j.neurobiolaging.2016.07.001 PG 9 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA EA9OP UT WOS:000386973900017 PM 27498053 ER PT J AU Bras, J Djaldetti, R Alves, AM Mead, S Darwent, L Lleo, A Molinuevo, JL Blesa, R Singleton, A Hardy, J Clarimon, J Guerreiro, R AF Bras, Jose Djaldetti, Ruth Alves, Ana Margarida Mead, Simon Darwent, Lee Lleo, Alberto Luis Molinuevo, Jose Blesa, Rafael Singleton, Andrew Hardy, John Clarimon, Jordi Guerreiro, Rita TI Exome sequencing in a consanguineous family clinically diagnosed with early-onset Alzheimer's disease identifies a homozygous CTSF mutation SO NEUROBIOLOGY OF AGING LA English DT Article DE Early onset Alzheimer's disease; Kufs disease; Recessive; Exome sequencing; Homozygosity; CTSF ID NEURONAL CEROID-LIPOFUSCINOSIS; B KUFS-DISEASE; EXTENDED TRACTS; CANDIDATE GENES; GENOME ANALYSIS; FRAMEWORK; DEMENTIA AB We have previously reported the whole genome genotyping analysis of 2 consanguineous siblings clinically diagnosed with early onset Alzheimer's disease (AD). In this analysis, we identified several large regions of homozygosity shared between both affected siblings, which we suggested could be candidate loci for a recessive genetic lesion underlying the early onset AD in these cases. We have now performed exome sequencing in one of these siblings and identified the potential cause of disease: the CTSF c.1243G>A:p. Gly415Arg mutation in homozygosity. Biallelic mutations in this gene have been shown to cause Type B Kufs disease, an adult-onset neuronal ceroid lipofuscinosis with some cases resembling the impairment seen in AD. (C) 2016 Elsevier Inc. All rights reserved. C1 [Bras, Jose; Alves, Ana Margarida; Darwent, Lee; Hardy, John; Guerreiro, Rita] UCL, Inst Neurol, Dept Mol Neurosci, 1 Wakefield St 1st Floor, London WC1N 1PJ, England. [Bras, Jose; Guerreiro, Rita] Univ Aveiro, Dept Med Sci, Aveiro, Portugal. [Bras, Jose; Guerreiro, Rita] Univ Aveiro, Inst Biomed iBiMED, Aveiro, Portugal. [Djaldetti, Ruth] Rabin Med Ctr, Dept Neurol, Beilinson Campus, Petah Tiqwa, Israel. [Djaldetti, Ruth] Felsenstein Res Ctr, Petah Tiqwa, Israel. [Djaldetti, Ruth] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel. [Mead, Simon] UCL, Inst Neurol, Dept Neurodegenerat Dis, MRC Prion Unit, London, England. [Lleo, Alberto; Blesa, Rafael; Clarimon, Jordi] Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Neurol, Memory Unit, Barcelona, Spain. [Lleo, Alberto; Blesa, Rafael; Clarimon, Jordi] Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, St Pau Biomed Res Inst, Barcelona, Spain. [Lleo, Alberto] Ctr Networked Biomed Res Neurodegenerat Dis, CIBERNED, Madrid, Spain. [Luis Molinuevo, Jose] Hosp Clin Barcelona, Inst Neurosci, Dept Neurol, Alzheimers Dis & Other Cognit Disorders Unit, Barcelona, Spain. [Luis Molinuevo, Jose] Univ Barcelona, IDIBAPS, Barcelona, Spain. [Singleton, Andrew] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Guerreiro, R (reprint author), UCL, Inst Neurol, Dept Mol Neurosci, 1 Wakefield St 1st Floor, London WC1N 1PJ, England. EM r.guerreiro@ucl.ac.uk RI Hardy, John/C-2451-2009 FU Medical Research Council (UK); National Institute of Health Research's Biomedical Research Centre and Biomedical Research Unit (Dementia) at UCL Hospitals NHS Foundation Trust; Alzheimer's Society; European Grand Prix for Young Researcher-SCOR - Fondation pour la Recherche sur Alzheimer FX This work was supported in part by an anonymous donor; the Medical Research Council (UK) and by the National Institute of Health Research's Biomedical Research Centre and Biomedical Research Unit (Dementia) at UCL Hospitals NHS Foundation Trust; fellowships from the Alzheimer's Society to Jose Bras and Rita Guerreiro, and by the 2014 European Grand Prix for Young Researcher-SCOR awarded by the Fondation pour la Recherche sur Alzheimer to Rita Guerreiro. The authors would like to thank the Exome Aggregation Consortium and the groups that provided exome variant data for comparison. A full list of contributing groups can be found at http://exac.broadinstitute.org/about. NR 22 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD OCT PY 2016 VL 46 AR 236.e1 DI 10.1016/j.neurobiolaging.2016.06.018 PG 6 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA EA9OP UT WOS:000386973900025 PM 27524508 ER PT J AU Sassi, C Nalls, MA Ridge, PG Gibbs, JR Ding, JH Lupton, MK Troakes, C Lunnon, K Al-Sarraj, S Brown, KS Medway, C Clement, N Lord, J Turton, J Bras, J Almeida, MR Holstege, H Louwersheimer, E Van Der Flier, WM Scheltens, P Van Swieten, JC Santana, I Oliveira, C Morgan, K Powell, JF Kauwe, JS Cruchaga, C Goate, AM Singleton, AB Guerreiro, R Hardy, J AF Sassi, Celeste Nalls, Michael A. Ridge, Perry G. Gibbs, Jesse R. Ding, Jinhui Lupton, Michelle K. Troakes, Claire Lunnon, Katie Al-Sarraj, Safa Brown, Kristelle S. Medway, Christopher Clement, Naomi Lord, Jenny Turton, James Bras, Jose Almeida, Maria R. Holstege, Henne Louwersheimer, Eva van der Flier, Wiesje M. Scheltens, Philip Van Swieten, John C. Santana, Isabel Oliveira, Catarina Morgan, Kevin Powell, John F. Kauwe, John S. Cruchaga, Carlos Goate, Alison M. Singleton, Andrew B. Guerreiro, Rita Hardy, John CA ARUK Consortium TI ABCA7 p.G215S as potential protective factor for Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's disease (AD); Genome-wide association studies (GWASs); ABCA7; Whole exome sequencing (WES); Whole genome sequencing (WGS); Protective variant ID GENOME-WIDE ASSOCIATION; IDENTIFIES VARIANTS; APOLIPOPROTEIN-E; COMMON VARIANTS; SEQUENCING DATA; RARE VARIANTS; RISK; LOCI; EXPRESSION; SUSCEPTIBILITY AB Genome-wide association studies (GWASs) have been effective approaches to dissect common genetic variability underlying complex diseases in a systematic and unbiased way. Recently, GWASs have led to the discovery of over 20 susceptibility loci for Alzheimer's disease (AD). Despite the evidence showing the contribution of these loci to AD pathogenesis, their genetic architecture has not been extensively investigated, leaving the possibility that low frequency and rare coding variants may also occur and contribute to the risk of disease. We have used exome and genome sequencing data to analyze the single independent and joint effect of rare and low-frequency protein coding variants in 9 AD GWAS loci with the strongest effect sizes after APOE (BIN1, CLU, CR1, PICALM, MS4A6A, ABCA7, EPHA1, CD33, and CD2AP) in a cohort of 332 sporadic AD cases and 676 elderly controls of British and North-American ancestry. We identified coding variability in ABCA7 as contributing to AD risk. This locus harbors a low-frequency coding variant (p. G215S, rs72973581, minor allele frequency = 4.3%) conferring a modest but statistically significant protection against AD (p-value = 0.024, odds ratio = 0.57, 95% confidence interval = 0.41-0.80). Notably, our results are not driven by an enrichment of loss of function variants in ABCA7, recently reported as main pathogenic factor underlying AD risk at this locus. In summary, our study confirms the role of ABCA7 in AD and provides new insights that should address functional studies. (C) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license. C1 [Sassi, Celeste; Bras, Jose; Guerreiro, Rita; Hardy, John] UCL Inst Neurol, Dept Mol Neurosci, Weston Res Labs, Reta Lila, London, England. [Sassi, Celeste; Nalls, Michael A.; Gibbs, Jesse R.; Ding, Jinhui; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Sassi, Celeste] Charite, Ctr Stroke Res Berlin CSB, Dept Expt Neurol, Berlin, Germany. [Sassi, Celeste] German Ctr Neurodegenerat Dis DZNE, Berlin Site, Germany. [Ridge, Perry G.; Kauwe, John S.] Brigham Young Univ, Dept Biol, Provo, UT 84602 USA. [Lupton, Michelle K.; Troakes, Claire; Lunnon, Katie; Al-Sarraj, Safa; Powell, John F.] Kings Coll London, Inst Psychiat Psychol & Neurosci, London, England. [Lupton, Michelle K.] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia. [Lunnon, Katie] Univ Exeter, Sch Med, Inst Biomed & Clin Sci, Exeter, Devon, England. [Brown, Kristelle S.; Medway, Christopher; Clement, Naomi; Lord, Jenny; Turton, James; Morgan, Kevin] Univ Nottingham, Queens Med Ctr, Sch Life Sci, Translat Cell Sci Human Genet, Nottingham, England. [Almeida, Maria R.] Univ Coimbra, Ctr Neurosci & Cell Biol, Neurogenet Lab, Coimbra, Portugal. [Holstege, Henne; Louwersheimer, Eva; van der Flier, Wiesje M.; Scheltens, Philip; Van Swieten, John C.] Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Dept Neurol, Neurosci Campus Amsterdam, Amsterdam, Netherlands. [Van Swieten, John C.] Erasmus MC, Dept Neurol, Rotterdam, Netherlands. [Santana, Isabel] Ctr Hosp & Univ Coimbra, Neurol Dept, Coimbra, Portugal. [Santana, Isabel] Univ Coimbra, Fac Med, Coimbra, Portugal. [Oliveira, Catarina] Univ Coimbra, CNC Ctr Neurosci & Cell Biol, Coimbra, Portugal. [Oliveira, Catarina] Univ Coimbra, Fac Med, Biochem Lab, Coimbra, Portugal. [Powell, John F.] Brigham Young Univ, Dept Neurosci, Provo, UT 84602 USA. [Cruchaga, Carlos] Washington Univ, Div Biol & Biomed Sci, St Louis, MO USA. [Goate, Alison M.] Icahn Sch Med Mt Sinai, Icahn Med Inst, New York, NY 10029 USA. RP Hardy, J (reprint author), UCL Inst Neurol, Dept Mol Neurosci, Weston Res Labs, Reta Lila, London, England. EM j.hardy@ucl.ac.uk RI Powell, John/G-4412-2011; Hardy, John/C-2451-2009; OI Powell, John/0000-0001-6124-439X; Todd, Stephen/0000-0002-2312-9195 FU Alzheimer's Research UK; Medical Research Council (MRC); Wellcome Trust/MRC Joint Call in Neurodegeneration award [WT089698]; National Institute for Health Research Biomedical Research Unit in Dementia at University College London Hospitals, University College London; Intramural Research Programs of the National Institute on Aging; National Institute of Neurological Disease and Stroke; National Institutes of Health (Department of Health and Human Services) [ZO1 AG000950-10]; ARUK; AS; Intramural Research Program of the National Institute on Aging; National Institutes of Health; Department of Health and Human Services [ZO1 AG000950-10]; National Institute on Aging (NIA) [U24 AG21886]; NIH [R01 AG042611]; [P50 AG016574]; [U01 AG006786]; [R01 AG18023] FX This study was supported by the Alzheimer's Research UK, the Medical Research Council (MRC), the Wellcome Trust/MRC Joint Call in Neurodegeneration award (WT089698) to the UK Parkinson's Disease Consortium (whose members are from the University College London Institute of Neurology, the University of Sheffield, and the MRC Protein Phosphorylation Unit at the University of Dundee), grants (P50 AG016574, U01 AG006786, and R01 AG18023), the National Institute for Health Research Biomedical Research Unit in Dementia at University College London Hospitals, University College London; an anonymous donor, the Big Lottery (to Dr. Morgan); a fellowship from Alzheimer's Research UK (to Dr. Guerreiro); and the Intramural Research Programs of the National Institute on Aging and the National Institute of Neurological Disease and Stroke, National Institutes of Health (Department of Health and Human Services Project number, ZO1 AG000950-10). The MRC London Neurodegenerative Diseases Brain Bank and the Manchester Brain Bank from Brains for Dementia Research are jointly funded from ARUK and AS. This work was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services, project number ZO1 AG000950-10. Samples from the National Cell Repository for Alzheimer's Disease (NCRAD), which receives government support under a cooperative agreement grant (U24 AG21886) awarded by the National Institute on Aging (NIA), were used in this study. NIH grant R01 AG042611 to Kauwe J. NR 37 TC 0 Z9 0 U1 4 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 EI 1558-1497 J9 NEUROBIOL AGING JI Neurobiol. Aging PD OCT PY 2016 VL 46 AR 235.e1 DI 10.1016/j.neurobiolaging.2016.04.004 PG 9 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA EA9OP UT WOS:000386973900023 PM 27289440 ER PT J AU Knittel, G Liedgens, P Korovkina, D Seeger, JM Al-Baldawi, Y Al-Maarri, M Fritz, C Vlantis, K Bezhanova, S Scheel, AH Wolz, OO Reimann, M Moller, P Lopez, C Staudt, LM Ortmann, M Pasparakis, M Siebert, R Schmitt, CA Klatt, AR Wunderlich, FT Schafer, SC Persigehl, T Montesinos-Rongen, M Odenthal, M Buttner, R Frenzel, LP Kashkar, H Reinhardt, HC AF Knittel, G. Liedgens, P. Korovkina, D. Seeger, J. M. Al-Baldawi, Y. Al-Maarri, M. Fritz, C. Vlantis, K. Bezhanova, S. Scheel, A. H. Wolz, O. -O. Reimann, M. Moeller, P. Lopez, C. Staudt, L. M. Ortmann, M. Pasparakis, M. Siebert, R. Schmitt, C. A. Klatt, A. R. Wunderlich, F. T. Schaefer, S. C. Persigehl, T. Montesinos-Rongen, M. Odenthal, M. Buettner, R. Frenzel, L. P. Kashkar, H. Reinhardt, H. C. TI B cell-specific conditional expression of Myd88 p.L252P leads to the development of diffuse large B cell lymphoma in mice SO ONCOLOGY RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 [Knittel, G.; Liedgens, P.; Korovkina, D.; Fritz, C.; Frenzel, L. P.; Reinhardt, H. C.] Univ Hosp Cologne, Dept Internal Med 1, Cologne, Germany. [Seeger, J. M.; Kashkar, H.] Univ Hosp Cologne, Inst Microbiol & Hyg, Cologne, Germany. [Al-Baldawi, Y.; Persigehl, T.] Univ Hosp Cologne, Dept Radiol, Cologne, Germany. [Al-Maarri, M.; Wunderlich, F. T.] Max Planck Inst Metab Res, Cologne, Germany. [Vlantis, K.; Pasparakis, M.] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, Cologne, Germany. [Bezhanova, S.] NN Blokhin Russian Canc Res Ctr, Moscow, Russia. [Scheel, A. H.; Ortmann, M.; Schaefer, S. C.; Odenthal, M.; Buettner, R.] Univ Hosp Cologne, Inst Pathol, Cologne, Germany. [Wolz, O. -O.] Univ Tubingen, Interfac Inst Cell Biol, Dept Immunol, Tubingen, Germany. [Reimann, M.; Schmitt, C. A.] Charite Univ Med Ctr, Dept Hematol Oncol, Berlin, Germany. [Moeller, P.] Univ Ulm, Fac Med, Inst Pathol, Ulm, Germany. [Lopez, C.; Siebert, R.] Univ Kiel, Kiel, Germany. [Lopez, C.; Siebert, R.] Univ Hosp Schleswig Holstein, Inst Human Genet, Kiel, Germany. [Staudt, L. M.] NCI, NIH, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Klatt, A. R.] Univ Hosp Cologne, Inst Clin Chem, Cologne, Germany. [Montesinos-Rongen, M.] Univ Hosp Cologne, Inst Neuropathol, Cologne, Germany. NR 0 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 2296-5270 EI 2296-5262 J9 ONCOL RES TREAT JI Oncol. Res. Treat. PD OCT PY 2016 VL 39 SU 3 MA V717 BP 218 EP 219 PG 2 WC Oncology SC Oncology GA DZ2SK UT WOS:000385691300538 ER PT J AU Smit, RAJ Postmus, I Trompet, S Barnes, MR Warren, H Arsenault, BJ Chasman, DI Cupples, LA Hitman, GA Krauss, RM Li, XH Psaty, BM Stein, CM Rotter, JI Jukema, JW AF Smit, Roelof A. J. Postmus, Iris Trompet, Stella Barnes, Michael R. Warren, Helen Arsenault, Benoit J. Chasman, Daniel I. Cupples, L. Adrienne Hitman, Graham A. Krauss, Ronald M. Li, Xiaohui Psaty, Bruce M. Stein, Charles M. Rotter, Jerome I. Jukema, J. Wouter TI Rooted in risk: genetic predisposition for low-density lipoprotein cholesterol level associates with diminished low-density lipoprotein cholesterol response to statin treatment SO PHARMACOGENOMICS LA English DT Article DE MR-Egger; pharmacogenetics; statin therapy ID MENDELIAN RANDOMIZATION; LDL-CHOLESTEROL; HEART-DISEASE; NPC1L1; METAANALYSIS; EZETIMIBE; THERAPY; BIAS AB Aims: To utilize previously reported lead SNPs for low-density lipoprotein cholesterol (LDL-c) levels to find additional loci of importance to statin response, and examine whether genetic predisposition to LDL-c levels associates with differential statin response. Methods: We investigated effects on statin response of 59 LDL-c SNPs, by combining summary level statistics from the Global Lipids Genetics and Genomic Investigation of Statin Therapy consortia. Results: Lead SNPs for APOE, SORT1 and NPC1L1 were associated with a decreased LDL-c response to statin treatment, as was overall genetic predisposition for increased LDL-c levels as quantified with 59 SNPs, with a 5.4% smaller statin response per standard deviation increase in genetically raised LDL-c levels. Conclusion: Genetic predisposition for increased LDL-c level may decrease efficacy of statin therapy. C1 [Smit, Roelof A. J.; Trompet, Stella; Jukema, J. Wouter] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands. [Smit, Roelof A. J.; Postmus, Iris; Trompet, Stella] Leiden Univ, Med Ctr, Dept Internal Med, Sect Gerontol & Geriatr, Leiden, Netherlands. [Barnes, Michael R.; Warren, Helen] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med, London EC1M 6BQ, England. [Barnes, Michael R.; Warren, Helen] Queen Mary Univ London, Barts & London Sch Med, NIHR Barts Cardiovasc Biomed Res Unit, London EC1M 6BQ, England. [Arsenault, Benoit J.] Inst Univ Cardiol & Pneumol Quebec, Ctr Rech, Quebec City, PQ, Canada. [Chasman, Daniel I.] Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA. [Chasman, Daniel I.] Harvard Univ, Harvard Med Sch, Boston, MA 02115 USA. [Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Hitman, Graham A.] Queen Mary Univ London, Blizard Inst, Barts & London Sch Med & Dent, London EC1M 6BQ, England. [Krauss, Ronald M.] Childrens Hosp Oakland, Res Inst, Dept Atherosclerosis Res, Oakland, CA 94609 USA. [Li, Xiaohui; Rotter, Jerome I.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA. [Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98101 USA. [Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA 98101 USA. [Stein, Charles M.] Vanderbilt Univ, Dept Med, Nashville, TN 37232 USA. [Stein, Charles M.] Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37232 USA. [Jukema, J. Wouter] Leiden Univ, Med Ctr, Einthoven Lab Expt Vasc Med, Leiden, Netherlands. [Jukema, J. Wouter] Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands. RP Smit, RAJ (reprint author), Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.; Smit, RAJ (reprint author), Leiden Univ, Med Ctr, Dept Internal Med, Sect Gerontol & Geriatr, Leiden, Netherlands. EM r.a.j.smit@lumc.nl FU Steering Committee of the Yale Open Data Access Project by Johnson Johnson; JUPITER from AstraZeneca; Netherlands Heart Foundation [2001 D 032] FX BM Psaty serves on the Data and Safety Monitoring Board of a clinical trial funded by the manufacturer, and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. DI Chasman received research support for independent genetic analysis in JUPITER from AstraZeneca. JW Jukema is an Established Clinical Investigator of The Netherlands Heart Foundation (grant no. 2001 D 032). RM Krauss serves on the Merck Global Atherosclerosis Advisory Board. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 26 TC 0 Z9 0 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 EI 1744-8042 J9 PHARMACOGENOMICS JI Pharmacogenomics PD OCT PY 2016 VL 17 IS 15 BP 1621 EP 1628 DI 10.2217/pgs-2016-0091 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA EA3UD UT WOS:000386529900003 PM 27648687 ER PT J AU Pereira, TA Syn, WK Amancio, FF Cunha, PHD Caporali, JFM Trindade, GVD Santos, ET Souza, MM Andrade, ZA Witek, RP Secor, WE Pereira, FEL Lambertucci, JR Diehl, AM AF Pereira, Thiago Almeida Syn, Wing-Kin Amancio, Frederico Figueiredo Diniz Cunha, Pedro Henrique Morais Caporali, Julia Fonseca de Melo Trindade, Guilherme Vaz Santos, Elisangela Trindade Souza, Marcia Maria Andrade, Zilton Araujo Witek, Rafal P. Secor, William Evan Lima Pereira, Fausto Edmundo Lambertucci, Jose Roberto Diehl, Anna Mae TI Osteopontin Is Upregulated in Human and Murine Acute Schistosomiasis Mansoni SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID GRANULOMA-FORMATION; LIVER; INFLAMMATION; INFECTION; RESPONSES; FIBROSIS; INJURY; CELLS AB Background Symptomatic acute schistosomiasis mansoni is a systemic hypersensitivity reaction against the migrating schistosomula and mature eggs after a primary infection. The mechanisms involved in the pathogenesis of acute schistosomiasis are not fully elucidated. Osteopontin has been implicated in granulomatous reactions and in acute hepatic injury. Our aims were to evaluate if osteopontin plays a role in acute Schistosoma mansoni infection in both human and experimentally infected mice and if circulating OPN levels could be a novel biomarker of this infection. Methodology/Principal Findings Serum/plasma osteopontin levels were measured by ELISA in patients with acute (n = 28), hepatointestinal (n = 26), hepatosplenic (n = 39) schistosomiasis and in uninfected controls (n = 21). Liver osteopontin was assessed by immunohistochemistry in needle biopsies of 5 patients. Sera and hepatic osteopontin were quantified in the murine model of schistosomiasis mansoni during acute (7 and 8 weeks post infection, n = 10) and chronic (30 weeks post infection, n = 8) phase. Circulating osteopontin levels are increased in patients with acute schistosomiasis (p = 0.0001). The highest levels of OPN were observed during the peak of clinical symptoms (7-11 weeks post infection), returning to baseline level once the granulomas were modulated (>12 weeks post infection). The plasma levels in acute schistosomiasis were even higher than in hepatosplenic patients. The murine model mirrored the human disease. Macrophages were the major source of OPN in human and murine acute schistosomiasis, while the ductular reaction maintains OPN production in hepatosplenic disease. Soluble egg antigens from S. mansoni induced OPN expression in primary human kupffer cells. Conclusions/Significance S. mansoni egg antigens induce the production of OPN by macrophages in the necroticexudative granulomas characteristic of acute schistosomiasis mansoni. Circulating OPN levels are upregulated in human and murine acute schistosomiasis and could be a noninvasive biomarker of this form of disease. C1 [Pereira, Thiago Almeida; Diehl, Anna Mae] Duke Univ, Med Ctr, Dept Med, Div Gastroenterol, Durham, NC 27710 USA. [Pereira, Thiago Almeida; Amancio, Frederico Figueiredo; Diniz Cunha, Pedro Henrique; Morais Caporali, Julia Fonseca; de Melo Trindade, Guilherme Vaz; Lambertucci, Jose Roberto] Univ Fed Minas Gerais, Fac Med, Dept Clin Med, Lab Doencas Infecciosas & Parasitarias, Belo Horizonte, MG, Brazil. [Pereira, Thiago Almeida; Santos, Elisangela Trindade; Souza, Marcia Maria; Andrade, Zilton Araujo] Fundacao Oswaldo Cruz, Ctr Pesquisas Goncalo Moniz, Lab Patol Expt, Salvador, BA, Brazil. [Pereira, Thiago Almeida] NIAID, Immunopathogesis Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Syn, Wing-Kin] Ralph H Johnson Vet Affairs Med Ctr, Gastroenterol Sect, Charleston, SC USA. [Syn, Wing-Kin] Med Univ South Carolina, Div Gastroenterol & Hepatol, Charleston, SC USA. [Syn, Wing-Kin] Fdn Liver Res, Inst Hepatol, Liver Regenerat & Repair Res Grp, London, England. [de Melo Trindade, Guilherme Vaz] Natl Univ Ireland, Sch Med, Dept Physiol, Galway, Ireland. [Witek, Rafal P.] Thermo Fisher Sci, Frederick, MD USA. [Secor, William Evan] Ctr Dis Control & Prevent, Atlanta, GA USA. [Lima Pereira, Fausto Edmundo] Univ Fed Espirito Santo, Nucleo Doencas Infecciosas, Vitoria, ES, Brazil. RP Diehl, AM (reprint author), Duke Univ, Med Ctr, Dept Med, Div Gastroenterol, Durham, NC 27710 USA.; Lambertucci, JR (reprint author), Univ Fed Minas Gerais, Fac Med, Dept Clin Med, Lab Doencas Infecciosas & Parasitarias, Belo Horizonte, MG, Brazil. EM jrlambertu@gmail.com; annamae.diehl@duke.edu FU National Institutes of Health [R01-DK-077794]; National Institutes of Health (Division of Intramural Research, NIAID, NIH); Duke University; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Ministry of Science, Technology and Innovation of Brazil (CNPq); Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) FX This work was supported by National Institutes of Health (grant number R01-DK-077794 (to AMD); Division of Intramural Research, NIAID, NIH (to TAP)); the Duke University Endowment (the Florence McAlister Professorship) (to AMD), the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Ministry of Science, Technology and Innovation of Brazil (CNPq) (to TAP, FELP, JRL and ZAA); and Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) (to JRL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2016 VL 10 IS 10 AR e0005057 DI 10.1371/journal.pntd.0005057 PG 13 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA EA5QH UT WOS:000386676200038 PM 27755536 ER PT J AU Tomashek, KM Rivera, A Torres-Velasquez, B Hunsperger, EA Munoz-Jordan, JL Sharp, TM Rivera, I Sanabria, D Blau, DM Galloway, R Torres, J Rodriguez, R Serrano, J Chavez, C Davila, F Perez-Padilla, J Ellis, EM Caballero, G Wright, L Zaki, SR Deseda, C Rodriguez, E Margolis, HS AF Tomashek, Kay M. Rivera, Aidsa Torres-Velasquez, Brenda Hunsperger, Elizabeth A. Munoz-Jordan, Jorge L. Sharp, Tyler M. Rivera, Irma Sanabria, Dario Blau, Dianna M. Galloway, Renee Torres, Jose Rodriguez, Rosa Serrano, Javier Chavez, Carlos Davila, Francisco Perez-Padilla, Janice Ellis, Esther M. Caballero, Gladys Wright, Laura Zaki, Sherif R. Deseda, Carmen Rodriguez, Edda Margolis, Harold S. TI Enhanced Surveillance for Fatal Dengue-Like Acute Febrile Illness in Puerto Rico, 2010-2012 SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; CONSENSUS CONFERENCE; HEMORRHAGIC-FEVER; CASE-MANAGEMENT; SHOCK SYNDROME; PCR ASSAY; RT-PCR; DIAGNOSIS; VIRUS; EPIDEMIC AB Background Dengue is a leading cause of morbidity throughout the tropics; however, accurate population- based estimates of mortality rates are not available. Methods/Principal Findings We established the Enhanced Fatal Acute Febrile Illness Surveillance System (EFASS) to estimate dengue mortality rates in Puerto Rico. Healthcare professionals submitted serum and tissue specimens from patients who died from a dengue-like acute febrile illness, and death certificates were reviewed to identify additional cases. Specimens were tested for markers of dengue virus (DENV) infection by molecular, immunologic, and immunohistochemical methods, and were also tested for West Nile virus, Leptospira spp., and other pathogens based on histopathologic findings. Medical records were reviewed and clinical data abstracted. A total of 311 deaths were identified, of which 58 (19%) were DENV laboratory-positive. Dengue mortality rates were 1.05 per 100,000 population in 2010, 0.16 in 2011 and 0.36 in 2012. Dengue mortality was highest among adults 19-64 years and seniors >= 65 years (1.17 and 1.66 deaths per 100,000, respectively). Other pathogens identified included 34 Leptospira spp. cases and one case of Burkholderia pseudomallei and Neisseria meningitidis. Conclusions/Significance EFASS showed that dengue mortality rates among adults were higher than reported for influenza, and identified a leptospirosis outbreak and index cases of melioidosis and meningitis. C1 [Tomashek, Kay M.; Rivera, Aidsa; Torres-Velasquez, Brenda; Hunsperger, Elizabeth A.; Munoz-Jordan, Jorge L.; Sharp, Tyler M.; Perez-Padilla, Janice; Ellis, Esther M.; Margolis, Harold S.] Ctr Dis Control & Prevent CDC, Dengue Branch, Div Vector Borne Dis, San Juan, PR 00920 USA. [Rivera, Irma; Sanabria, Dario; Torres, Jose; Rodriguez, Rosa; Serrano, Javier; Chavez, Carlos; Davila, Francisco; Rodriguez, Edda] Puerto Rico Inst Forens Sci, San Juan, PR USA. [Blau, Dianna M.; Zaki, Sherif R.] CDC, Infect Dis Pathol Branch, Div High Consequence Pathogens & Pathol, Atlanta, GA 30333 USA. [Galloway, Renee] CDC, Bacterial Special Pathogens Branch, Div High Consequence Pathogens, Atlanta, GA 30333 USA. [Caballero, Gladys] Demog Registry Puerto Rico, San Juan, PR USA. [Wright, Laura] ATSDR, Geospatial Res Anal & Serv Program, Div Toxicol & Human Hlth Sci, Atlanta, GA USA. [Deseda, Carmen] Puerto Rico Dept Hlth, San Juan, PR USA. [Tomashek, Kay M.] NIAID, Off Clin Res Resources, Div Microbiol & Infect Dis, NIH, Rockville, MD USA. RP Tomashek, KM (reprint author), Ctr Dis Control & Prevent CDC, Dengue Branch, Div Vector Borne Dis, San Juan, PR 00920 USA.; Tomashek, KM (reprint author), NIAID, Off Clin Res Resources, Div Microbiol & Infect Dis, NIH, Rockville, MD USA. EM kay.tomashek@nih.gov FU CDC Dengue Branch programmatic FX The authors received CDC Dengue Branch programmatic funding for this project. No additional sources of funding were received. The funders had no role in the system design, data collection and analysis, decision to publish or preparation of the manuscript. NR 61 TC 0 Z9 0 U1 3 U2 3 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 OCT PY 2016 VL 10 IS 10 AR e0005025 DI 10.1371/journal.pntd.0005025 PG 19 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA EA5QH UT WOS:000386676200018 PM 27727271 ER PT J AU Meacham, E Orem, J Nakigudde, G Zujewski, JA Rao, D AF Meacham, Elizabeth Orem, Jackson Nakigudde, Gertrude Zujewski, Jo Anne Rao, Deepa TI Exploring stigma as a barrier to cancer service engagement with breast cancer survivors in Kampala, Uganda SO PSYCHO-ONCOLOGY LA English DT Article DE cancer; oncology; qualitative; stigma; Uganda AB ObjectiveTo understand the role of stigma in the delay of cancer service engagement by women with breast cancer in Kampala, Uganda. BackgroundWomen in Sub-Saharan African countries are twice as likely to die from cancer as women in high-income countries, which is largely attributable to late diagnosis. While breast cancer-related stigma has been identified in Sub-Saharan Africa, limited research focuses on how stigma impacts the behavior of breast cancer patients in Uganda. MethodsThis qualitative study used a grounded theory approach to examine illness narratives from 20 breast cancer survivors in Uganda, gathered through semistructured interviews. ResultsThematic analysis showed that perceived and internalized stigma associated with breast cancer influenced care engagement throughout illness, delaying engagement and inhibiting treatment completion. Women identified key factors for overcoming stigma including acceptance of diagnosis, social support, and understanding of breast cancer. ConclusionThe growing burden of mortality associated with breast cancer in Uganda can be mitigated by improving early detection and treatment engagement through interventions which account for key psychosocial barriers such as stigma. C1 [Meacham, Elizabeth] Univ Washington, Dept Global Hlth, Seattle, WA USA. [Orem, Jackson] Uganda Canc Inst, Kampala, Uganda. [Nakigudde, Gertrude] Uganda Womens Canc Support Org UWOCASO, Kampala, Uganda. [Zujewski, Jo Anne] NCI, Rockville, MD USA. [Rao, Deepa] Univ Washington, Dept Global Hlth, Dept Psychiat & Behav Sci, Seattle, WA USA. RP Meacham, E (reprint author), Univ Washington, Dept Global Hlth, Seattle, WA USA. EM elizabeth.meacham@gmail.com FU National Cancer Institute - Center for Global Health FX We are indebted to all of the breast cancer survivors in Uganda who were willing to share their illness experiences. This project was funded through a contract from the National Cancer Institute - Center for Global Health. NR 13 TC 1 Z9 1 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2016 VL 25 IS 10 SI SI BP 1206 EP 1211 DI 10.1002/pon.4215 PG 6 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA DZ3CA UT WOS:000385720300011 PM 27421234 ER PT J AU Blair, KS Otero, M Teng, C Geraci, M Lewis, E Hollon, N Blair, RJR Ernst, M Grillon, C Pine, DS AF Blair, K. S. Otero, M. Teng, C. Geraci, M. Lewis, E. Hollon, N. Blair, R. J. R. Ernst, Monique Grillon, C. Pine, D. S. TI Learning from other people's fear: amygdala-based social reference learning in social anxiety disorder SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Amygdala; emotions; imaging; medial prefrontal cortex; social anxiety ID EMOTIONAL EXPRESSIONS; FACIAL EXPRESSIONS; FRONTAL-CORTEX; PHOBIA; FACES; BRAIN; ACTIVATION; ANGRY; SELF; MECHANISMS AB Background Social anxiety disorder involves fear of social objects or situations. Social referencing may play an important role in the acquisition of this fear and could be a key determinant in future biomarkers and treatment pathways. However, the neural underpinnings mediating such learning in social anxiety are unknown. Using event-related functional magnetic resonance imaging, we examined social reference learning in social anxiety disorder. Specifically, would patients with the disorder show increased amygdala activity during social reference learning, and further, following social reference learning, show particularly increased response to objects associated with other people's negative reactions? Method A total of 32 unmedicated patients with social anxiety disorder and 22 age-, intelligence quotient- and gender-matched healthy individuals responded to objects that had become associated with others' fearful, angry, happy or neutral reactions. Results During the social reference learning phase, a significant group x social context interaction revealed that, relative to the comparison group, the social anxiety group showed a significantly greater response in the amygdala, as well as rostral, dorsomedial and lateral frontal and parietal cortices during the social, relative to non-social, referencing trials. In addition, during the object test phase, relative to the comparison group, the social anxiety group showed increased bilateral amygdala activation to objects associated with others' fearful reactions, and a trend towards decreased amygdala activation to objects associated with others' happy and neutral reactions. Conclusions These results suggest perturbed observational learning in social anxiety disorder. In addition, they further implicate the amygdala and dorsomedial prefrontal cortex in the disorder, and underscore their importance in future biomarker developments. C1 [Blair, K. S.; Otero, M.; Teng, C.; Geraci, M.; Lewis, E.; Hollon, N.; Blair, R. J. R.; Ernst, Monique; Grillon, C.; Pine, D. S.] NIMH, Dept Hlth & Human Serv, NIH, 15K North Dr,Room 115A,MSC 2670, Bethesda, MD 20892 USA. RP Blair, KS (reprint author), NIMH, Dept Hlth & Human Serv, NIH, 15K North Dr,Room 115A,MSC 2670, Bethesda, MD 20892 USA. EM peschark@mail.nih.gov FU National Institutes of Health, National Institute of Mental Health FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Mental Health. The authors have no financial disclosures to report. Further, the authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. NR 35 TC 0 Z9 0 U1 4 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 EI 1469-8978 J9 PSYCHOL MED JI Psychol. Med. PD OCT PY 2016 VL 46 IS 14 BP 2943 EP 2953 DI 10.1017/S0033291716001537 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA EA5DN UT WOS:000386639700006 PM 27476529 ER PT J AU Carlson, BA Tobe, R Yefremova, E Tsuji, PA Hoffmann, VJ Schweizer, U Gladyshev, VN Hatfield, DL Conrad, M AF Carlson, Bradley A. Tobe, Ryuta Yefremova, Elena Tsuji, Petra A. Hoffmann, Victoria J. Schweizer, Ulrich Gladyshev, Vadim N. Hatfield, Dolph L. Conrad, Marcus TI Glutathione peroxidase 4 and vitamin E cooperatively prevent hepatocellular degeneration SO REDOX BIOLOGY LA English DT Article DE Selenoprotein; Ferroptosis; Lipid peroxidation ID THIOREDOXIN REDUCTASE; CELL-DEATH; TARGETED DISRUPTION; EMBRYONIC LETHALITY; MOUSE DEVELOPMENT; OXIDATIVE STRESS; ALPHA-TOCOPHEROL; GENE-EXPRESSION; UGA CODONS; SELENOCYSTEINE AB The selenoenzyme glutathione peroxidase 4 (Gpx4) is an essential mammalian glutathione peroxidase, which protects cells against detrimental lipid peroxidation and governs a novel form of regulated necrotic cell death, called ferroptosis. To study the relevance of Gpx4 and of another vitally important selenoprotein, cytosolic thioredoxin reductase (Txnrd1), for liver function, mice with conditional deletion of Gpx4 in hepatocytes were studied, along with those lacking Txnrd1 and selenocysteine (Sec) tRNA (Trsp) in hepatocytes. Unlike Txnrd1- and Trsp-deficient mice, Gpx4(-/-) mice died shortly after birth and presented extensive hepatocyte degeneration. Similar to Txnrd1-deficient livers, Gpx4(-/-) livers manifested upregulation of nuclear factor (erythroid-derived)-like 2 (Nrf2) response genes. Remarkably, Gpx4(-/-) pups born from mothers fed a vitamin E-enriched diet survived, yet this protection was reversible as subsequent vitamin E deprivation caused death of Gpx4-deficient mice similar to 4 weeks thereafter. Abrogation of selenoprotein expression in Gpx4(-/-) mice did not result in viable mice, indicating that the combined deficiency aggravated the loss of Gpx4 in liver. By contrast, combined Trsp/Txnrd1-deficient mice were born, but had significantly shorter lifespans than either single knockout, suggesting that Txnrd1 plays an important role in supporting liver function of mice lacking Trsp. In sum our study demonstrates that the ferroptosis regulator Gpx4 is critical for hepatocyte survival and proper liver function, and that vitamin E can compensate for its loss by protecting cells against deleterious lipid peroxidation. Published by Elsevier B.V. C1 [Carlson, Bradley A.; Tobe, Ryuta; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Mouse Canc Genet Program, NIH, 37 Convent Dr,Bldg 37,Room 5016, Bethesda, MD 20892 USA. [Yefremova, Elena; Conrad, Marcus] Helmholtz Zentrum Munchen, Inst Dev Genet, Neuherberg, Germany. [Tsuji, Petra A.] Towson Univ, Dept Biol Sci, Towson, MD USA. [Hoffmann, Victoria J.] NIH, Off Director Diagnost & Res Serv Branch, Bldg 10, Bethesda, MD 20892 USA. [Schweizer, Ulrich] Univ Bonn, Inst Biochem & Mol Biol, Bonn, Germany. [Gladyshev, Vadim N.] Harvard Med Sch, Dept Med, Div Genet, Brigham & Womens Hosp, Boston, MA USA. RP Hatfield, DL (reprint author), NCI, Mol Biol Selenium Sect, Mouse Canc Genet Program, NIH, 37 Convent Dr,Bldg 37,Room 5016, Bethesda, MD 20892 USA.; Conrad, M (reprint author), Helmholtz Zentrum Munchen, Inst Dev Genet, Neuherberg, Germany. EM hatfield@mail.nih.gov; marcus.conrad@helmholtz-muenchen.de OI Conrad, Marcus/0000-0003-1140-5612; Schweizer, Ulrich/0000-0003-1380-4780 FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research; Deutsche Forschungsgemeinschaft [CO 291/2-3, CO 291/5-1]; Human Frontier Science Program [RGP0013/14] FX We are grateful to Jose Pedro Friedmann Angeli for critical reading of the manuscript. DLH was funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. MC received funding from the Deutsche Forschungsgemeinschaft (CO 291/2-3; CO 291/5-1) and the Human Frontier Science Program (RGP0013/14). NR 39 TC 6 Z9 6 U1 10 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2317 J9 REDOX BIOL JI Redox Biol. PD OCT PY 2016 VL 9 BP 22 EP 31 DI 10.1016/j.redox.2016.05.003 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA EA6RQ UT WOS:000386757000003 PM 27262435 ER PT J AU Childs, R Blaise, D AF Childs, Richard Blaise, Didier TI Alternative Donor Allogeneic Transplants: Introduction SO SEMINARS IN HEMATOLOGY LA English DT Editorial Material C1 [Childs, Richard] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. [Blaise, Didier] Ctr Rech Cancerol Marseille, Marseille, France. RP Childs, R (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. EM childsr@nhlbi.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-1963 EI 1532-8686 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 2016 VL 53 IS 4 BP 219 EP 220 DI 10.1053/j.seminhematol.2016.08.003 PG 2 WC Hematology SC Hematology GA EB1FL UT WOS:000387094900001 PM 27788758 ER PT J AU van Besien, K Childs, R AF van Besien, Koen Childs, Richard TI Haploidentical cord transplantation-The best of both worlds SO SEMINARS IN HEMATOLOGY LA English DT Article DE Alternative donor transplant; Umbilical cord blood; Third-party progenitors ID HEMATOPOIETIC-CELL TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; ALTERNATIVE DONOR TRANSPLANTATION; RELAPSE-FREE SURVIVAL; HOST DISEASE-FREE; BLOOD TRANSPLANTATION; BONE-MARROW; OUTCOMES; UNIT; ENGRAFTMENT AB Haploidentical (haplo)-cord transplantation combines infusion of an umbilical cord blood (UCB) unit with CD34-selected cells usually from human leukocyte antigen (HLA) mismatched donors. Initial rapid count recovery from the haplo-hematopoietic progenitors, is gradually replaced by durable engraftment from UCB progenitors. UCB grafts used for haplo-cord are smaller, but better matched than those required for single or double UCB stem cell transplant (SCT). More than 200 patients with hematological malignancies have been transplanted. Median age was 54 years (range 17-74) and 77 were over age 60. One-year survival was 64% for patients with intermediate- and low-risk disease, with no deaths beyond 2 years. In high-risk disease, 1-year survival was 44%. In a comparison with patients undergoing double UCB SCT, haplo-cord transplant resulted in faster hematopoietic recovery, lower rates of acute and chronic graft-versus-host disease (GVHD), lower rates of disease recurrence, and improved GVHD- and relapse-free survival (GRFS). Excellent results were also reported for patients with aplastic anemia where 18 of 21 patients had sustained cord blood engraftment. Rates of GVHD and of disease recurrence after haplo-cord are encouraging. However, in the approximately 10% of patients with failure of the UCB graft disease recurrence is high, supporting the important role of UCB-mediated graft-versus-leukemia (GVL). Ongoing efforts are aimed at identifying determinants of UCB engraftment, at reducing rates of disease recurrence in high risk patients and at optimizing dose and schedule of ATG -necessary to avoid early haplo-graft rejection, but also contributing to early post-transplant immunocompromise. For those lacking haploidentical donors, unrelated donors have been successfully utilized. (C) 2016 Elsevier Inc. All rights reserved. C1 [van Besien, Koen] Weill Cornell Med, Div Hematol Oncol, 520 E 70th St, New York, NY 10021 USA. [Childs, Richard] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. RP van Besien, K (reprint author), Weill Cornell Med, Div Hematol Oncol, 520 E 70th St, New York, NY 10021 USA. EM kov9001@med.cornell.edu FU Miltenyi Biotec (Germany) FX Dr. van Besien's research was supported by an unrestricted grant from Miltenyi Biotec (Germany). NR 38 TC 1 Z9 1 U1 2 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 0037-1963 EI 1532-8686 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 2016 VL 53 IS 4 BP 257 EP 266 DI 10.1053/j.seminhematol.2016.07.004 PG 10 WC Hematology SC Hematology GA EB1FL UT WOS:000387094900007 PM 27788764 ER PT J AU Truog, WE Higgins, RD AF Truog, William E. Higgins, Rosemary D. TI The Neonatal Research Network Introduction SO SEMINARS IN PERINATOLOGY LA English DT Editorial Material C1 [Truog, William E.] Univ Missouri, Sch Med, Childrens Mercy Hosp, Kansas City, MO 64108 USA. [Higgins, Rosemary D.] Eunice Kennedy Shriner Natl Inst Child Hlth, Human Dev, NIH, Bethesda, MD USA. RP Truog, WE (reprint author), Univ Missouri, Sch Med, Childrens Mercy Hosp, Kansas City, MO 64108 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0146-0005 EI 1558-075X J9 SEMIN PERINATOL JI Semin. Perinatol. PD OCT PY 2016 VL 40 IS 6 BP 335 EP 336 DI 10.1053/j.semperi.2016.05.001 PG 2 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA EA3XX UT WOS:000386543700001 PM 27344191 ER PT J AU Higgins, RD Shankaran, S AF Higgins, Rosemary D. Shankaran, Seetha TI The Neonatal Research Network: History since 2003, future directions and challenges SO SEMINARS IN PERINATOLOGY LA English DT Review DE Neonatal; Research; Infant; Trial; Study ID EXTREMELY PRETERM INFANTS; NEURODEVELOPMENTAL OUTCOMES; EARLY CPAP; ENCEPHALOPATHY; HYPOTHERMIA; MORTALITY; DISEASE; GROWTH; AGE AB The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neontal Research Network (NRN) was established in 1986 in response to the need for rigorous studies to guide care and management of sick and premature newborns. The network is comprise of clinical centers that perform clinical protocols to investigate the safety and efficay of treatment and management strategies for newborn infants as well as a data cordinating center. Infrastructure is set up for observational and interventional studies as well as neurodevelopmental follow-up of patients. The network has conducted trials and observational studies on major neonatal problems including pulmonary disease, neuroprotection, sepsis and infection, necrotizing enterocolitis, vaccine administration to preterm infants, retinopathy of prematurity, cardiovascular issues including blood pressure, human milk, growth and nutrition, hematologic issues, resuscitation, pulmonary hypertension, and neurodevelopmental outcome. This mechanism of clinical research for newborns has led to changes in care practices leading to improved outcomes for high-risk infants. Published by Elsevier Inc. C1 [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, 6710B Rockledge Dr,Room 2233,MSC 7002, Bethesda, MD 20892 USA. [Shankaran, Seetha] Wayne State Univ, Sch Med, Dept Pediat, Div Neonatal Perinatal Med, Detroit, MI 48201 USA. RP Higgins, RD (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, 6710B Rockledge Dr,Room 2233,MSC 7002, Bethesda, MD 20892 USA. EM higginsr@mail.nih.gov FU Intramural NIH HHS [Z99 HD999999]; NICHD NIH HHS [U10 HD021385, UG1 HD027853] NR 18 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0146-0005 EI 1558-075X J9 SEMIN PERINATOL JI Semin. Perinatol. PD OCT PY 2016 VL 40 IS 6 BP 337 EP 340 DI 10.1053/j.semperi.2016.05.002 PG 4 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA EA3XX UT WOS:000386543700002 PM 27371959 ER PT J AU Das, A Tyson, J Pedroza, C Schmidt, B Gantz, M Wallace, D Truog, WE Higgins, RD AF Das, Abhik Tyson, Jon Pedroza, Claudia Schmidt, Barbara Gantz, Marie Wallace, Dennis Truog, William E. Higgins, Rosemary D. TI Methodological issues in the design and analyses of neonatal research studies: Experience of the NICHD Neonatal Research Network SO SEMINARS IN PERINATOLOGY LA English DT Review DE Statistical methodology; Trial design; Competing outcomes; Randomization of multiples; Causal inference ID LOW-BIRTH-WEIGHT; EXTREMELY PRETERM INFANTS; CLUSTER-RANDOMIZED-TRIAL; SEMICOMPETING RISKS DATA; WEEKS GESTATIONAL-AGE; CLINICAL-TRIALS; MULTIPLE BIRTHS; NEURODEVELOPMENTAL OUTCOMES; BRONCHOPULMONARY DYSPLASIA; PROPENSITY SCORE AB Impressive advances in neonatology have occurred over the 30 years of life of The Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN). However, substantial room for improvement remains in investigating and further developing the evidence base for improving outcomes among the extremely premature. We discuss some of the specific methodological challenges in the statistical design and analysis of randomized trials and observational studies in this population. Challenges faced by the NRN include designing trials for unusual or rare outcomes, accounting for and explaining center variations, identifying other subgroup differences, and balancing safety and efficacy concerns between short-term hospital outcomes and longer-term neurodevelopmental outcomes. In conclusion, the constellation of unique patient characteristics in neonates calls for broad understanding and careful consideration of the issues identified in this article for conducting rigorous studies in this population. (C) 2016 Elsevier Inc. All rights reserved. C1 [Das, Abhik] RTI Int, Biostat & Epidemiol Div, 6110 Execut Blvd,Suite 902, Rockville, MD 20852 USA. [Tyson, Jon; Pedroza, Claudia] Univ Texas Hlth Sci Ctr Houston, Ctr Clin Res & Evidence Based Med, Houston, TX 77030 USA. [Schmidt, Barbara] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA. [Gantz, Marie; Wallace, Dennis] RTI Int, Biostat & Epidemiol Div, Res Triangle Pk, NC USA. [Truog, William E.] Univ Missouri, Sch Med, Childrens Mercy Hosp & Clin, Kansas City, MO 64108 USA. [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Hlth & Human Dev, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA. RP Das, A (reprint author), RTI Int, Biostat & Epidemiol Div, 6110 Execut Blvd,Suite 902, Rockville, MD 20852 USA. EM adas@rti.org FU NICHD NIH HHS [U10 HD021373, UG1 HD027853, U10 HD036790, UG1 HD068244, UG1 HD068284, UG1 HD087229] NR 80 TC 1 Z9 1 U1 1 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 0146-0005 EI 1558-075X J9 SEMIN PERINATOL JI Semin. Perinatol. PD OCT PY 2016 VL 40 IS 6 BP 374 EP 384 DI 10.1053/j.semperi.2016.05.005 PG 11 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA EA3XX UT WOS:000386543700007 PM 27344192 ER PT J AU Archer, SW Carlo, WA Truog, WE Stevenson, DK Van Meurs, KP Sanchez, PJ Das, A Devaskar, U Nelin, LD Huitema, CMP Crawford, MM Higgins, RD AF Archer, Stephanie Wilson Carlo, Waldemar A. Truog, William E. Stevenson, David K. Van Meurs, Krisa P. Sanchez, Pablo J. Das, Abhik Devaskar, Uday Nelin, Leif D. Huitema, Carolyn M. Petrie Crawford, Margaret M. Higgins, Rosemary D. CA Eunice Kennedy Shriver Natl Inst TI Improving publication rates in a collaborative clinical trials research network SO SEMINARS IN PERINATOLOGY LA English DT Review DE Publication rates; Network collaboration; Authorship policies AB Unpublished results can bias biomedical literature, favoring positive over negative findings, primary over secondary analyses, and can lead to duplicate studies that unnecessarily endanger subjects and waste resources. The Neonatal Research Network's (NRN) publication policies for approving, reviewing, and tracking abstracts and papers work to combat these problems. In 2003, the NRN restricted investigators with unfinished manuscripts from proposing new ones and in 2010, urged authors to complete long-outstanding manuscripts. Data from 1991 to 2015 were analyzed to determine effectiveness of these policy changes. The NRN has achieved an overall publication rate of 78% for abstracts. For 1990-2002, of 137 abstracts presented, 43 (31%) were published within 2 years; for 2003-2009, after the manuscript completion policy was instituted, of 140 abstracts presented, 68 (49%) were published within 2 years. Following the effort in 2010, the rate increased to 64%. The NRN surpassed reported rates by developing a comprehensive process, holding investigators accountable and tracking abstracts from presentation to publication. (C) 2016 Published by Elsevier Inc. C1 [Archer, Stephanie Wilson; Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, NICHD Pregnancy & Perinatol Branch, 6710B Rockledge Dr,2321B, Bethesda, MD 20817 USA. [Carlo, Waldemar A.] Univ Alabama Birmingham, Div Neonatol, Birmingham, AL USA. [Truog, William E.] Univ Missouri, Sch Med, Dept Pediat, Childrens Mercy Hosp, Kansas City, MO 64108 USA. [Stevenson, David K.; Van Meurs, Krisa P.] Stanford Univ, Sch Med, Dept Pediat, Div Neonatal & Dev Med, Palo Alto, CA 94304 USA. [Stevenson, David K.; Van Meurs, Krisa P.] Lucile Packard Childrens Hosp, Palo Alto, CA USA. [Sanchez, Pablo J.] Univ Texas Southwestern Med Ctr Dallas, Dept Pediat, Dallas, TX USA. [Sanchez, Pablo J.; Nelin, Leif D.] Nationwide Childrens Hosp, Div Neonatol, Columbus, OH USA. [Das, Abhik; Huitema, Carolyn M. Petrie; Crawford, Margaret M.] RTI Int, Social Stat & Environm Sci Unit, Rockville, MD USA. [Devaskar, Uday] Univ Calif Los Angeles, David Geffen Sch Med, Div Neonatol & Dev Biol, Los Angeles, CA 90095 USA. RP Archer, SW (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, NICHD Pregnancy & Perinatol Branch, 6710B Rockledge Dr,2321B, Bethesda, MD 20817 USA. EM archerst@mail.nih.gov FU National Institutes of Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Center for Research Resources; National Center for Advancing Translational Sciences FX The National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Center for Research Resources, and the National Center for Advancing Translational Sciences provided grant support for the Neonatal Research Network. The content of the publication is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 9 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0146-0005 EI 1558-075X J9 SEMIN PERINATOL JI Semin. Perinatol. PD OCT PY 2016 VL 40 IS 6 BP 410 EP 417 DI 10.1053/j.semperi.2016.05.003 PG 8 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA EA3XX UT WOS:000386543700011 PM 27423510 ER PT J AU Ginexi, EM Vollinger, RE AF Ginexi, Elizabeth M. Vollinger, Robert E., Jr. TI National Cancer Institute's leadership role in promoting State and Community Tobacco Control research SO TOBACCO CONTROL LA English DT Editorial Material DE Environment; Media; Prevention; Public policy; Secondhand smoke ID UNITED-STATES; SMOKING; DISPARITIES; ADULTS; US AB The National Cancer Institute (NCI) has been at the vanguard of funding tobacco control research for decades with major efforts such as the Community Intervention Trial for Smoking Cessation (COMMIT) in 1988 and the American Stop Smoking Intervention Study (ASSIST) in 1991, followed by the Tobacco Research Initiative for State and Community Interventions in 1999. Most recently, in 2011, the NCI launched the State and Community Tobacco Control (SCTC) Research Initiative to address gaps in secondhand smoke policies, tax and pricing policies, mass media countermeasures, community and social norms and tobacco marketing. The initiative supported large scale research projects and time-sensitive ancillary pilot studies in response to expressed needs of state and community partners. This special issue of Tobacco Control showcases exciting findings from the SCTC. In this introductory article, we provide a brief account of NCI's historical commitment to promoting research to inform tobacco control policy. C1 [Ginexi, Elizabeth M.; Vollinger, Robert E., Jr.] NCI, Tobacco Control Res Branch, 9609 Med Ctr Dr,Room 3E564,MSC 9761, Bethesda, MD 20892 USA. RP Ginexi, EM (reprint author), NCI, Tobacco Control Res Branch, 9609 Med Ctr Dr,Room 3E564,MSC 9761, Bethesda, MD 20892 USA. EM LGinexi@mail.nih.gov NR 21 TC 0 Z9 0 U1 1 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 EI 1468-3318 J9 TOB CONTROL JI Tob. Control PD OCT PY 2016 VL 25 SU 1 BP i4 EP i5 DI 10.1136/tobaccocontrol-2016-053153 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA EA2ZF UT WOS:000386465600002 PM 27697941 ER PT J AU Williams, B Mirmonsef, P Boucher, CA Bushman, F Carrington-Lawrence, S Collman, RG Dandekar, S Dang, Q Malaspina, A Paredes, R Stone, A Landay, A AF Williams, Brett Mirmonsef, Paria Boucher, Charles A. B. Bushman, Frederic Carrington-Lawrence, Stacy Collman, Ronald G. Dandekar, Satya Que Dang Malaspina, Angela Paredes, Roger Stone, Arthur Landay, Alan TI A Summary of the First HIV Microbiome Workshop 2015 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article DE HIV; microbiome; immune activation; microbial translocation ID IMMUNODEFICIENCY-VIRUS-INFECTION; EPITHELIAL BARRIER DYSFUNCTION; SYSTEMIC IMMUNE ACTIVATION; TRIMETHYLAMINE-N-OXIDE; BACTERIAL VAGINOSIS; GUT MICROBIOTA; VAGINAL MICROBIOTA; GENITAL-TRACT; T-CELLS; MUCOSAL AB The role of microbiota in the pathogenesis of HIV infection has become the subject of intense research in recent years. A rapidly growing amount of data suggest that microbial dysbiosisin the gut or the genital tractcan influence HIV transmission and/or disease progression; however, a deeper understanding of the mechanisms involved is lacking. To better understand the relationship between the microbiome and HIV infection, investigators from a wide variety of disciplines, including those working in basic and clinical HIV studies, cardiovascular disease, reproductive health, and bioinformatics, gathered at the first International Workshop on Microbiome in HIV Pathogenesis, Prevention and Treatment, at NIH on 7 and 8 April, 2015. C1 [Williams, Brett] Rush Univ, Med Ctr, Div Infect Dis, 600 South Paulina Suite 143, Chicago, IL 60612 USA. [Mirmonsef, Paria; Landay, Alan] Rush Univ, Med Ctr, Dept Immunol Microbiol, Chicago, IL 60612 USA. [Boucher, Charles A. B.] Erasmus Univ, Dept Virosci, Erasmus Med Ctr, Rotterdam, Netherlands. [Bushman, Frederic] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Carrington-Lawrence, Stacy] US Natl Inst Hlth, Off AIDS Res, Div Program Coordinat Planning & Strateg Initiat, Off Director,US Dept Hlth & Human Serv, Philadelphia, PA USA. [Collman, Ronald G.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Dandekar, Satya] Univ Calif Davis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA. [Que Dang; Malaspina, Angela] NIAID, Vaccine Res Program, Div AIDS, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Paredes, Roger] Univ Vic, Univ Autonoma Barcelona, Inst Recerca, SIDA IrsiCaixa, Catalonia, Spain. [Paredes, Roger] Univ Vic, Univ Autonoma Barcelona, Unitat VIH, Catalonia, Spain. [Stone, Arthur] NIAID, HJF DAIDS, NIH, DHHS, Bethesda, MD USA. RP Williams, B (reprint author), Rush Univ, Med Ctr, Div Infect Dis, 600 South Paulina Suite 143, Chicago, IL 60612 USA. EM brett_williams@rush.edu FU NHLBI NIH HHS [R01 HL113252, U01 HL098957, U01 HL112712]; NIAID NIH HHS [P30 AI045008]; NIMH NIH HHS [R01 MH061139] NR 56 TC 0 Z9 0 U1 2 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT-NOV PY 2016 VL 32 IS 10-11 BP 935 EP 941 DI 10.1089/aid.2016.0034 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA DZ9RL UT WOS:000386216200001 PM 27267576 ER PT J AU Porter, KA Turpin, J Begg, L Brown, G Chakhtoura, N Church, E Grossman, C Wira, C Veronese, F AF Porter, Kristen A. Turpin, Jim Begg, Lisa Brown, Gina Chakhtoura, Nahida Church, Elizabeth Grossman, Cynthia Wira, Charles Veronese, Fulvia TI Understanding the Intersection of Young Age, Mucosal Injury, and HIV Susceptibility SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Review DE HIV; HIV; AIDS pathogenesis; HIV transmission; HIV prevention; mucosal ID INTIMATE PARTNER VIOLENCE; FEMALE REPRODUCTIVE-TRACT; GENITOANAL INJURY; MENSTRUAL-CYCLE; VAGINAL TRANSMISSION; SEXUAL VIOLENCE; WOMEN; ADOLESCENT; RISK; METAANALYSIS AB Adolescent boys and girls are disproportionately affected in the current HIV epidemic. Numerous sociobehavioral studies have addressed the indirect drivers surrounding this vulnerabilityfor example, socioeconomic, geographical locale, and all forms of violence. However, the direct factors that may influence infection, such as the anatomical and physiological maturation of the anogenital tracts of adolescents or the trauma and wound-healing processes of injured mucosal tissue, are understudied and represent a gap within the HIV prevention field. This article reviews the epidemiology of HIV infection and violence in adolescents and the available basic science knowledge attending this research area. More importantly, this review highlights the most critical gaps that need to be addressed to design preventive interventions that are safe and effective for this population, which is key to ending the HIV pandemic. C1 [Porter, Kristen A.; Turpin, Jim; Church, Elizabeth; Veronese, Fulvia] NIAID, Div Aids, NIH, Room 8B53,MSC9831,5601 Fishers Lane, Bethesda, MD 20852 USA. [Begg, Lisa] NIH, Off Res Womens Hlth, Bldg 10, Bethesda, MD 20892 USA. [Brown, Gina] NIH, Off AIDS Res, Bldg 10, Bethesda, MD 20892 USA. [Chakhtoura, Nahida] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Grossman, Cynthia] NIMH, Div AIDS Res, NIH, Rockville, MD 20857 USA. [Wira, Charles] Dartmouth Coll, Geisel Sch Med, Hanover, NH 03755 USA. [Porter, Kristen A.] Westfield State Univ, Dept Biol, Westfield, MA USA. [Grossman, Cynthia] FasterCures, Washington, DC USA. RP Veronese, F (reprint author), NIAID, Div Aids, NIH, Room 8B53,MSC9831,5601 Fishers Lane, Bethesda, MD 20852 USA. EM fv10x@nih.gov FU NIAID NIH HHS [R01 AI117739] NR 52 TC 0 Z9 0 U1 3 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT-NOV PY 2016 VL 32 IS 10-11 BP 1149 EP 1158 DI 10.1089/aid.2016.0206 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA DZ9RL UT WOS:000386216200026 PM 27726428 ER PT J AU Opitz, JM Biesecker, LG Hennekam, RC AF Opitz, John M. Biesecker, Leslie G. Hennekam, Raoul C. TI GAUDEAMUS IGITUR...In gratitude to John Carey for his stewardship of the American Journal of Medical Genetics 2001-2016 SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Editorial Material C1 [Opitz, John M.] Univ Utah, Sch Med, Dept Pediat Med Genet, Salt Lake City, UT USA. [Opitz, John M.] Univ Utah, Sch Med, Dept Human Genet, Salt Lake City, UT 84132 USA. [Opitz, John M.] Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA. [Opitz, John M.] Univ Utah, Sch Med, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA. [Biesecker, Leslie G.] NHGRI, NIH, Bethesda, MD 20892 USA. [Hennekam, Raoul C.] Acad Med Ctr, Dept Pediat, Amsterdam, Netherlands. RP Opitz, JM (reprint author), Univ Utah, Sch Med, Dept Pediat, Div Med Genet, 295 Chipeta Way, Salt Lake City, UT 84108 USA. EM john.opitz@hsc.utah.edu NR 1 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD OCT PY 2016 VL 170 IS 10 SI SI BP 2501 EP 2502 DI 10.1002/ajmg.a.37760 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA DW4KQ UT WOS:000383612200003 PM 27540900 ER PT J AU Gripp, KW Baker, L Kandula, V Conard, K Scavina, M Napoli, JA Griffin, GC Thacker, M Knox, RG Clark, GR Parker, VER Semple, R Mirzaa, G Keppler-Noreuil, KM AF Gripp, Karen W. Baker, Laura Kandula, Vinay Conard, Katrina Scavina, Mena Napoli, Joseph A. Griffin, Gregory C. Thacker, Mihir Knox, Rachel G. Clark, Graeme R. Parker, Victoria E. R. Semple, Robert Mirzaa, Ghayda Keppler-Noreuil, Kim M. TI Nephroblastomatosis or Wilms tumor in a fourth patient with a somatic PIK3CA mutation SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE Wilms tumor; nephroblastomatosis; PIK3CA-related overgrowth; hemihyperplasia; hemihypertrophy; CLOVES; lipoma; somatic mutation ID MARMORATA-TELANGIECTATICA-CONGENITA; PIK3CA-RELATED OVERGROWTH SPECTRUM; KLIPPEL-TRENAUNAY-SYNDROME; NEVI CLOVE-SYNDROME; VASCULAR MALFORMATIONS; LIPOMATOUS OVERGROWTH; ACTIVATING MUTATIONS; CHILDREN; RISK; HEMIHYPERTROPHY AB Wilms tumor and nephroblastomatosis are associated with syndromic conditions including hemihyperplasia. Hemihyperplasia is genetically heterogeneous and may be the result of genomic abnormalities seen in Beckwith-Wiedemann syndrome, mosaic chromosome or genomic abnormalities, or somatic point mutations. Somatic missense mutations affecting the PI3K-AKT-MTOR pathway result in segmental overgrowth and are present in numerous benign and malignant tumors. Here, we report a fourth patient with asymmetric overgrowth due to a somatic PIK3CA mutation who had nephroblastomatosis or Wilms tumor. Similar to two of three reported patients with a somatic PIK3CA mutation and renal tumors, he shared a PIK3CA mutation affecting codon 1047, presented at birth with asymmetric overgrowth, and had fibroadipose overgrowth. Codon 1047 is most commonly affected by somatic mutations in PIK3CA-related overgrowth spectrum (PROS). While the fibroadipose overgrowth phenotype appears to be common in individuals with PIK3CA mutations at codon 1047, individuals with a clinical diagnosis of Klippel-Trenaunay syndrome or isolated lymphatic malformation also had mutations affecting this amino acid. Screening for Wilms tumor in individuals with PROS-related hemihyperplasia may be considered and, until the natural history is fully elucidated in larger cohort studies, may follow guidelines for Beckwith-Wiedemann syndrome, or isolated hemihyperplasia. It is not known if the specific PIK3CA mutation, the mosaic distribution, or the clinical presentation affect the Wilms tumor or nephroblastomatosis risk in individuals with PROS. (c) 2016 Wiley Periodicals, Inc. C1 [Gripp, Karen W.; Baker, Laura; Kandula, Vinay; Conard, Katrina; Scavina, Mena; Napoli, Joseph A.; Griffin, Gregory C.; Thacker, Mihir] AI du Pont Hosp Children Nemours, Wilmington, DE 19803 USA. [Knox, Rachel G.; Clark, Graeme R.; Parker, Victoria E. R.; Semple, Robert] Univ Cambridge, Metab Res Labs, Inst Metab Sci, Cambridge, MA USA. [Mirzaa, Ghayda] Seattle Childrens Res Inst, Ctr Integrat Brain Res, Seattle, WA USA. [Keppler-Noreuil, Kim M.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Gripp, KW (reprint author), AI du Pont Hosp Children Nemours, Wilmington, DE 19803 USA. EM kgripp@nemours.org FU US National Institutes of Health under NINDS [K08NS092898]; Intramural Research Program of the National Human Genome Research Institute; Wellcome Trust [WT097721, WT098498]; Medical Research Council [MRC_MC_UU_12012/5]; United Kingdom National Institute for Health Research Rare Diseases Translational Research Collaboration FX Grant sponsor: US National Institutes of Health under NINDS; Grant number: K08NS092898; Grant sponsor: Intramural Research Program of the National Human Genome Research Institute; Grant sponsor: Wellcome Trust; Grant numbers: WT097721, WT098498; Grant sponsor: Medical Research Council; Grant number: MRC_MC_UU_12012/5; Grant sponsor: United Kingdom National Institute for Health Research Rare Diseases Translational Research Collaboration. NR 36 TC 2 Z9 2 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD OCT PY 2016 VL 170 IS 10 SI SI BP 2559 EP 2569 DI 10.1002/ajmg.a.37758 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA DW4KQ UT WOS:000383612200009 PM 27191687 ER PT J AU Keppler-Noreuil, KM Baker, EH Sapp, JC Lindhurst, MJ Biesecker, LG AF Keppler-Noreuil, Kim M. Baker, Eva H. Sapp, Julie C. Lindhurst, Marjorie J. Biesecker, Leslie G. TI Somatic AKT1 mutations cause meningiomas colocalizing with a characteristic pattern of cranial hyperostosis SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE AKT1 mutations; cranial hyperostosis; hemimegalencephaly; meningiomas; Proteus syndrome ID PROTEUS-SYNDROME; MOLECULAR-GENETICS; DIAGNOSTIC-CRITERIA; EN PLAQUE; SECONDARY; SKULL; BASE AB Somatic genetic mutations in meningiomas are associated with histologic subtypes, anatomical location, and grade. Concomitant hyperostosis occurs with some meningiomas and the pathogenesis is not well understood. Cranial hyperostosis and meningiomas are common in patients with Proteus syndrome, which is caused by a somatic activating mutation in AKT1 c.49G>A. This same mutation has also been found in 6-9% of sporadic non-syndromic meningiomas. Sixty-one patients with Proteus syndrome meeting clinical diagnostic criteria were evaluated at the NIH from 1997 to 2014. Of these 61, 52 had a somatic activating mutation (c.49G>A, p.Glu17Lys) in AKT1 confirmed from affected tissue samples. Photographs, physical examination and/or autopsy, X-rays, CT, and/or MRI scan of the head were reviewed in 29/52 patients. Of the 29 patients, the most common intracranial tumor was meningioma, all co-localizing with cranial hyperostosis, and diagnosed at younger ages than typical for isolated, non-syndromic meningiomas. These patients had progressive cranial overgrowth that consisted primarily of diploic space expansion, and was characterized by unilateral, parasagittal, and frontal bone involvement. We hypothesize that sporadic meningothelial and transitional subtype meningiomas are a forme fruste or microform of Proteus syndrome, and activation of the AKT/PI3K pathway drives hyperostosis in both non-syndromic, and Proteus-related meningiomas. (c) 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc. C1 [Keppler-Noreuil, Kim M.; Sapp, Julie C.; Lindhurst, Marjorie J.; Biesecker, Leslie G.] NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA. [Baker, Eva H.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. RP Keppler-Noreuil, KM (reprint author), NHGRI, NIH, 49 Convent Dr,4A83, Bethesda, MD 20892 USA. EM kim.keppler-noreuil@nih.gov FU National Human Genome Research Institute FX Grant sponsor: National Human Genome Research Institute. NR 22 TC 1 Z9 1 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD OCT PY 2016 VL 170 IS 10 SI SI BP 2605 EP 2610 DI 10.1002/ajmg.a.37737 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA DW4KQ UT WOS:000383612200017 PM 27550858 ER PT J AU AuYoung, M Linke, SE Pagoto, S Buman, MP Craft, LL Richardson, CR Hutber, A Marcus, BH Estabrooks, P Gorin, SS AF AuYoung, Mona Linke, Sarah E. Pagoto, Sherry Buman, Matthew P. Craft, Lynette L. Richardson, Caroline R. Hutber, Adrian Marcus, Bess H. Estabrooks, Paul Gorin, Sherri Sheinfeld TI Integrating Physical Activity in Primary Care Practice SO AMERICAN JOURNAL OF MEDICINE LA English DT Review DE Physical activity; Primary care; Socioecologic model ID HEALTH-CARE; ACTIVITY INTERVENTIONS; ACTIVITY PROMOTION; SOCIAL ECOLOGY; OBESITY PREVENTION; RANDOMIZED-TRIAL; ACTIVITY ADVICE; UNITED-STATES; WEIGHT-LOSS; EXERCISE AB Based on a collaborative symposium in 2014 hosted by the Society of Behavioral Medicine (SBM) and the American College of Sports Medicine (ACSM), this paper presents a model for physical activity counseling for primary care physicians (PCPs). Most US adults do not meet national recommendations for physical activity levels. Socioecological factors drive differences in physical activity levels by geography, sex, age, and racial/ethnic group. The recent Patient Protection and Affordable Care Act incentivizes PCPs to offer patients physical activity counseling. However, PCPs have reported socioecological barriers to physical activity counseling and also patient barriers to physical activity, spanning from the individual to the environmental (eg, lack of safe spaces for physical activity), policy (eg, reimbursement policies), and organizational (eg, electronic medical record protocols, worksite norms/policies) levels. The aims of this paper are to: 1) discuss barriers to PCP counseling for physical activity; 2) provide evidence-based strategies and techniques to help PCPs address these counseling barriers; and 3) suggest practical steps for PCPs to counsel patients on physical activity using strategies and supports from policy, the primary care team, and other support networks. (C) 2016 Elsevier Inc. All rights reserved. C1 [AuYoung, Mona] Ann Arbor VA Ctr Clin Management Res, Ann Arbor, MI USA. [Linke, Sarah E.; Marcus, Bess H.] Univ Calif San Diego, Dept Family Med & Publ Hlth, San Diego, CA 92103 USA. [Pagoto, Sherry] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. [Buman, Matthew P.] Arizona State Univ, Sch Nutr & Hlth Promot, Phoenix, AZ USA. [Craft, Lynette L.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Richardson, Caroline R.] Univ Michigan, Dept Family Med, Ann Arbor, MI 48109 USA. [Hutber, Adrian] ACSM, Indianapolis, IN USA. [Estabrooks, Paul] Univ Nebraska Med Ctr, Dept Hlth Promot Social & Behav Hlth, Omaha, NE USA. [Gorin, Sherri Sheinfeld] NYPAC, New York, NY USA. [Gorin, Sherri Sheinfeld] NIH, Leidos Biomed Res SAIC, Frederick, MD USA. RP Gorin, SS (reprint author), NYPAC, New York, NY USA.; Gorin, SS (reprint author), NCI, Leidos Biomed Res Inc, NIH, 3167 Fairbury Ln, Fairfax, VA 22031 USA. EM sherri.gorin@gmail.com FU Society of Behavioral Medicine (SBM); American College of Sports Medicine FX This paper resulted from an American College of Sports Medicine and Society of Behavioral Medicine (SBM) co-sponsored symposium for the SBM Annual Meeting, April 2014. NR 64 TC 1 Z9 1 U1 16 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD OCT PY 2016 VL 129 IS 10 BP 1022 EP 1029 DI 10.1016/j.amjmed.2016.02.008 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA EA1EA UT WOS:000386334100025 PM 26953063 ER PT J AU Gomez-Lopez, N Romero, R Xu, Y Miller, D Unkel, R MacKenzie, TC Frascoli, M Hassan, SS AF Gomez-Lopez, Nardhy Romero, Roberto Xu, Yi Miller, Derek Unkel, Ronald MacKenzie, Tippi C. Frascoli, Michela Hassan, Sonia S. TI Umbilical cord CD71+erythroid cells are reduced in neonates born to women in spontaneous preterm labor SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE cord blood; immunosuppression; neonates; parturition; placenta; pregnancy ID IMMATURE ERYTHROID-CELLS; INFECTION; NEWBORNS; BIRTH AB Problem: Preterm neonates are highly susceptible to infection. Neonatal host defense against infection seems to be maintained by the temporal presence of immunosuppressive CD71+ erythroid cells. The aim of this study was to investigate whether umbilical cord CD71+ erythroid cells are reduced in neonates born to women who undergo spontaneous preterm labor/birth. Method of study: Umbilical cord blood samples (n=155) were collected from neonates born to women who delivered preterm with (n=39) and without (n=12) spontaneous labor or at term with (n=82) and without (n=22) spontaneous labor. Time-matched maternal peripheral blood samples were also included (n=111). Mononuclear cells were isolated from these samples, and CD71+ erythroid cells were identified and quantified as CD3-CD235a+ CD71+ cells by flow cytometry. Results: (i) The proportion of CD71+ erythroid cells was 50-fold higher in cord blood than in maternal blood; (ii) a reduced number and frequency of umbilical cord CD71+ erythroid cells were found in neonates born to women who underwent spontaneous preterm labor compared to those born to women who delivered preterm without labor; (iii) umbilical cord CD71+ erythroid cells were fewer in neonates born to term pregnancies, regardless of the process of labor, than in those born to women who delivered preterm without labor; and (iv) no differences were seen in umbilical cord CD71+ erythroid cells between neonates born to women who -underwent spontaneous preterm labor and those born to women who delivered at term with labor. Conclusion: Umbilical cord CD71+ erythroid cells are reduced in neonates born to women who had undergone spontaneous preterm labor. C1 [Gomez-Lopez, Nardhy; Romero, Roberto; Xu, Yi; Miller, Derek; Unkel, Ronald; Hassan, Sonia S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NICHD,NIH,DHHS, Bethesda, MD USA. [Gomez-Lopez, Nardhy; Romero, Roberto; Xu, Yi; Miller, Derek; Unkel, Ronald; Hassan, Sonia S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NICHD,NIH,DHHS, Detroit, MI USA. [Gomez-Lopez, Nardhy; Xu, Yi; Miller, Derek; Unkel, Ronald; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Gomez-Lopez, Nardhy; Miller, Derek] Wayne State Univ, Sch Med, Dept Immunol & Microbiol, Detroit, MI 48201 USA. [Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [MacKenzie, Tippi C.; Frascoli, Michela] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med, San Francisco, CA 94143 USA. [MacKenzie, Tippi C.; Frascoli, Michela] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. RP Gomez-Lopez, N (reprint author), Wayne State Univ, Perinatol Res Branch, Dept Obstet & Gynecol, Sch Med,NICHD,NIH,DHHS, Detroit, MI 48202 USA.; Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, Detroit, MI 48202 USA. EM nardhy.gomez-lopez@wayne.edu; romeror@mail.nih.gov RI Gomez-Lopez, Nardhy/R-7664-2016 OI Gomez-Lopez, Nardhy/0000-0002-3406-5262 FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services (NICHD/NIH/DHHS); NICHD/NIH/DHHS [HHSN275201300006C]; Wayne State University Perinatal Initiative in Maternal, Perinatal and Child Health FX This research was supported, in part, by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services (NICHD/NIH/DHHS), and, in part, with federal funds from the NICHD/NIH/DHHS under Contract No. HHSN275201300006C. This research was also supported by the Wayne State University Perinatal Initiative in Maternal, Perinatal and Child Health. We thank the physicians and nurses from the Center for Advanced Obstetrical Care and Research and the Intrapartum Unit, as well as the research assistants from the PRB Clinical Laboratory, for their help in collecting human samples. We also thank staff members of the PRB Histology and Pathology Units for their examination of the pathological sections and Tara Mial for her critical readings of the manuscript. NR 19 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1046-7408 EI 1600-0897 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD OCT PY 2016 VL 76 IS 4 BP 280 EP 284 DI 10.1111/aji.12556 PG 5 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA EA1CP UT WOS:000386330400004 PM 27625200 ER PT J AU Olivier, KN AF Olivier, Kenneth N. TI Lady Windermere Dissected: More Form Than Fastidious SO ANNALS OF THE AMERICAN THORACIC SOCIETY LA English DT Editorial Material C1 [Olivier, Kenneth N.] NHLBI, Bldg 10, Bethesda, MD 20892 USA. RP Olivier, KN (reprint author), NHLBI, Cardiovasc & Pulm Branch, 10 Ctr Dr,MSC 1454,Bldg 10 CRC,Room 6-3130, Bethesda, MD 20832 USA. EM olivierk@nhlbi.nih.gov FU Intramural Research Program, National Heart, Lung and Blood Institute, National Institutes of Health FX Supported in part by the Intramural Research Program, National Heart, Lung and Blood Institute, National Institutes of Health. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1546-3222 EI 2325-6621 J9 ANN AM THORAC SOC JI Ann. Am. Thoracic Society PD OCT PY 2016 VL 13 IS 10 BP 1674 EP 1676 DI 10.1513/AnnalsATS.201607-521ED PG 3 WC Respiratory System SC Respiratory System GA DZ8KG UT WOS:000386118700003 PM 27726444 ER PT J AU Labonte, ME Kirkpatrick, SI Bell, RC Boucher, BA Csizmadi, I Koushik, A L'Abbe, MR Massarelli, I Robson, PJ Rondeau, I Shatenstein, B Subar, AF Lamarche, B AF Labonte, Marie-Eve Kirkpatrick, Sharon I. Bell, Rhonda C. Boucher, Beatrice A. Csizmadi, Ilona Koushik, Anita L'Abbe, Mary R. Massarelli, Isabelle Robson, Paula J. Rondeau, Isabelle Shatenstein, Bryna Subar, Amy F. Lamarche, Benoit TI Dietary assessment is a critical element of health research - Perspective from the Partnership for Advancing Nutritional and Dietary Assessment in Canada SO APPLIED PHYSIOLOGY NUTRITION AND METABOLISM LA English DT Article DE dietary analysis; nutrition; dietary intake; diet ID FOOD-FREQUENCY QUESTIONNAIRE; VALIDITY; WOMEN AB Challenges and complexities associated with assessing dietary intakes are numerous, but not insurmountable. This opinion paper from Canadian researchers draws attention to the importance of building capacity and providing funding opportunities for research in dietary assessment methods in Canada and elsewhere. Such strategies would contribute to a better understanding of the roles played by diet in human health and better translation of this information into the most meaningful and effective dietary guidelines, policies, and interventions. C1 [Labonte, Marie-Eve; Lamarche, Benoit] Univ Laval, Inst Nutr & Funct Foods, Sch Nutr, Quebec City, PQ G1V 0A6, Canada. [Kirkpatrick, Sharon I.] Univ Waterloo, Sch Publ Hlth & Hlth Syst, Waterloo, ON N2L 3G1, Canada. [Bell, Rhonda C.] Univ Alberta, Dept Agr Food & Nutr Sci, Div Human Nutr, Li Ka Shing Ctr Hlth Res Innovat, Edmonton, AB T6G 2E1, Canada. [Boucher, Beatrice A.] Canc Care Ontario, Prevent & Canc Control, Toronto, ON M5G 2L7, Canada. [Boucher, Beatrice A.] Univ Toronto, Dept Nutr Sci, Toronto, ON M5S 3E2, Canada. [Csizmadi, Ilona] Alberta Hlth Serv, CancerControl Alberta, Canc Epidemiol & Prevent Res, Calgary, AB T2S 3C3, Canada. [Koushik, Anita] Univ Montreal, CRCHUM, Montreal, PQ H2X 0A9, Canada. [Koushik, Anita] Univ Montreal, Dept Social & Prevent Med, Montreal, PQ H2X 0A9, Canada. [Labonte, Marie-Eve; L'Abbe, Mary R.] Univ Toronto, Dept Nutr Sci, Fac Med, Toronto, ON M5S 3E2, Canada. [Massarelli, Isabelle; Rondeau, Isabelle] Hlth Canada, Bur Food Surveillance & Sci Integrat, Food Directorate, Ottawa, ON K1A 0K9, Canada. [Robson, Paula J.] Alberta Hlth Serv, CancerControl Alberta, C MORE, Edmonton, AB T5J 3H1, Canada. [Shatenstein, Bryna] Univ Montreal, Dept Nutr, Ctr Rech, Inst Univ Geriatrie Montreal, Montreal, PQ H3W 1W5, Canada. [Subar, Amy F.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20814 USA. RP Lamarche, B (reprint author), Univ Laval, Inst Nutr & Funct Foods, Sch Nutr, Quebec City, PQ G1V 0A6, Canada.; Kirkpatrick, SI (reprint author), Univ Waterloo, Sch Publ Hlth & Hlth Syst, Waterloo, ON N2L 3G1, Canada. EM sharon.kirkpatrick@uwaterloo.ca; benoit.lamarche@fsaa.ulaval.ca OI Koushik, Anita/0000-0001-5304-7660 FU Canadian Cancer Society Research Institute [702855] FX B. L. and M. E. L. have developed a Web-based FFQ that is licensed for utilization by researchers and clinicians through formal agreements with Laval University's Research Office. User fees serve solely for the maintenance and upgrade of the dietary assessment tool. S. I. K. receives financial support from the Canadian Cancer Society Research Institute (grant no. 702855). R. C. B., B. A. B., I. C., A. K., M. R. L., I. M., P. J. R., I. R., B. S., A. F. S. report no conflicts of interest. NR 24 TC 3 Z9 3 U1 2 U2 2 PU CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS PI OTTAWA PA 65 AURIGA DR, SUITE 203, OTTAWA, ON K2E 7W6, CANADA SN 1715-5312 EI 1715-5320 J9 APPL PHYSIOL NUTR ME JI Appl. Physiol. Nutr. Metab. PD OCT PY 2016 VL 41 IS 10 BP 1096 EP 1099 DI 10.1139/apnm-2016-0146 PG 4 WC Nutrition & Dietetics; Physiology; Sport Sciences SC Nutrition & Dietetics; Physiology; Sport Sciences GA DZ8NZ UT WOS:000386128400014 ER PT J AU Nakamura, Y Mochida, A Choyke, PL Kobayashi, H AF Nakamura, Yuko Mochida, Ai Choyke, Peter L. Kobayashi, Hisataka TI Nanodrug Delivery: Is the Enhanced Permeability and Retention Effect Sufficient for Curing Cancer? SO BIOCONJUGATE CHEMISTRY LA English DT Review ID INTERSTITIAL FLUID PRESSURE; NEAR-INFRARED PHOTOIMMUNOTHERAPY; ENDOTHELIAL GROWTH-FACTOR; TUMOR-NECROSIS-FACTOR; ISOLATED LIMB PERFUSION; TEMPERATURE-SENSITIVE LIPOSOMES; INTENSITY FOCUSED ULTRASOUND; ELEVATING BLOOD-PRESSURE; TARGETED DRUG-DELIVERY; SOLID TUMORS AB Nanotechnology offers several attractive design features that have prompted its exploration for cancer diagnosis and treatment. Nanosized drugs have a large loading capacity, the ability to protect the payload from degradation, a large surface on which to conjugate targeting ligands, and controlled or sustained release. Nanosized drugs also leak preferentially into tumor tissue through permeable tumor vessels and are then retained in the tumor bed due to reduced lymphatic drainage. This process is known as the enhanced permeability and retention (EPR) effect. However, while the EPR effect is widely held to improve delivery of nanodrugs to tumors, it in fact offers less than a 2-fold increase in nanodrug delivery compared with critical normal organs, resulting in drug concentrations that are not sufficient for curing most cancers. In this Review, we first overview various barriers for nanosized drug delivery with an emphasis on the capillary wall's resistance, the main obstacle to delivering drugs. Then, we discuss current regulatory issues facing nanomedicine. Finally, we discuss how to make the delivery of nanosized drugs to tumors more effective by building on the EPR effect. C1 [Nakamura, Yuko; Mochida, Ai; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM kobayash@mail.nih.gov FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 165 TC 4 Z9 4 U1 47 U2 47 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 OCT PY 2016 VL 27 IS 10 BP 2225 EP 2238 DI 10.1021/acs.bioconjchem.6b00437 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA DZ6SK UT WOS:000385992000001 PM 27547843 ER PT J AU Jacobson, O Kiesewetter, DO Chen, XY AF Jacobson, Orit Kiesewetter, Dale O. Chen, Xiaoyuan TI Albumin-Binding Evans Blue Derivatives for Diagnostic Imaging and Production of Long-Acting Therapeutics SO BIOCONJUGATE CHEMISTRY LA English DT Review ID NEONATAL FC-RECEPTOR; MRI CONTRAST AGENT; IN-VIVO; RGD PEPTIDE; HALF-LIFE; POLYETHYLENE-GLYCOL; BOUND PACLITAXEL; SERUM-ALBUMIN; TUMOR-THERAPY; PLASMA-VOLUME AB One of the major design considerations for a drug is its pharmacokinetics: a drug with short blood half-life is less available at a target organ which in turn dictates treatment with either high or more frequent doses, and increases the likelihood of undesirable side effects. One method to improve drug pharmacokinetics is adding functional chemical groups to the drug molecule that can increase the half-life in the blood, hopefully, without significantly affecting its desired biological activity. Evans Blue (EB) dye reversibly binds to serum albumin with moderate affinity and has a long blood half-life. The binding of EB to albumin has been exploited to quantify protein leakage as an indicator of increased vascular permeability. Design of new chemical entities based on EB structure and coupling them to drugs, enables the usage of albumin as a reversible carrier in the blood and improves drug's half-life. This Topical Review summarizes the recent developments of various EB derivatives for molecular imaging and therapy applications. C1 [Jacobson, Orit; Kiesewetter, Dale O.; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. RP Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov NR 68 TC 0 Z9 0 U1 15 U2 15 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 OCT PY 2016 VL 27 IS 10 BP 2239 EP 2247 DI 10.1021/acs.bioconjchem.6b00487 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA DZ6SK UT WOS:000385992000002 ER PT J AU Francica, JR Lynn, GM Laga, R Joyce, MG Ruckwardt, TJ Morabito, KM Chen, M Chaudhuri, R Zhang, BS Sastry, M Druz, A Ko, K Choe, M Pechar, M Georgiev, IS Kueltzo, LA Seymour, LW Mascola, JR Kwong, PD Graham, BS Seder, RA AF Francica, Joseph R. Lynn, Geoffrey M. Laga, Richard Joyce, M. Gordon Ruckwardt, Tracy J. Morabito, Kaitlyn M. Chen, Man Chaudhuri, Rajoshi Zhang, Baoshan Sastry, Mallika Druz, Aliaksandr Ko, Kiyoon Choe, Misook Pechar, Michal Georgiev, Ivelin S. Kueltzo, Lisa A. Seymour, Leonard W. Mascola, John R. Kwong, Peter D. Graham, Barney S. Seder, Robert A. TI Thermoresponsive Polymer Nanoparticles Co-deliver RSV F Trimers with a TLR-7/8 Adjuvant SO BIOCONJUGATE CHEMISTRY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; T-CELL RESPONSES; DENDRITIC CELLS; IMMUNE-RESPONSES; FUSION GLYCOPROTEIN; RATIONAL DESIGN; INNATE IMMUNITY; VACCINE DEVELOPMENT; CROSS-PRESENTATION; NONHUMAN-PRIMATES AB Structure-based vaccine design has been used to develop immunogens that display conserved neutralization sites on pathogens such as HIV-1, respiratory syncytial virus (RSV), and influenza. Improving the immunogenicity of these designed immunogens with adjuvants will require formulations that do not alter protein antigenicity. Here, we show that nanoparticle-forming thermoresponsive polymers (TRP) allow for co-delivery of RSV fusion (F) protein trimers with Toll like receptor 7 and 8 agonists (TLR-7/8a) to enhance protective immunity. Although primary amine conjugation of TLR-7/8a to F trimers severely disrupted the recognition of critical neutralizing epitopes, F trimers site-selectively coupled to TRP nanoparticles retained appropriate antigenicity and elicited high titers of prefusion-specific, T(H)1 isotype anti-RSV F antibodies following vaccination. Moreover, coupling F trimers to TRP delivering TLR-7/8a resulted in similar to 3-fold higher binding and neutralizing antibody titers than soluble F trimers admixed with TLR-7/8a and conferred protection from intranasal RSV challenge. Overall, these data show that TRP nanoparticles may provide a broadly applicable platform for eliciting neutralizing antibodies to structure-dependent epitopes on RSV, influenza, HIV-1, or other pathogens. C1 [Francica, Joseph R.; Lynn, Geoffrey M.; Joyce, M. Gordon; Ruckwardt, Tracy J.; Morabito, Kaitlyn M.; Chen, Man; Zhang, Baoshan; Sastry, Mallika; Druz, Aliaksandr; Ko, Kiyoon; Choe, Misook; Georgiev, Ivelin S.; Mascola, John R.; Kwong, Peter D.; Graham, Barney S.; Seder, Robert A.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Laga, Richard; Pechar, Michal] Acad Sci Czech Republic, Inst Macromol Chem, CR-16206 Prague, Czech Republic. [Chaudhuri, Rajoshi; Kueltzo, Lisa A.] NIAID, Vaccine Prod Program, Vaccine Res Ctr, NIH, Gaithersburg, MD 20878 USA. [Seymour, Leonard W.] Univ Oxford, Dept Oncol, Oxford OX3 7DQ, England. RP Seder, RA (reprint author), NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. EM rseder@mail.nih.gov RI Pechar, Michal/G-6423-2014; Laga, Richard/G-3627-2014 FU Vaccine Research Center (NIAID, NIH); Czech Science Foundation [16-14957Y]; Ministry of Education, Youth and Sports of the Czech Republic [BIOCEV-FAR LQ1604] FX The authors acknowledge Marlon Dillon, Kefale Wuddie, Gloria Salbador, and Carmelo Chiedi for expert veterinary technical assistance; Azad Kumar for generously providing untagged RSV F proteins; and April Kilikelly, Joan Ngwuta, and Andrew Ishizuka for helpful discussion. This work was funded in part by the intramural research program of the Vaccine Research Center (NIAID, NIH). Further support was given by the Czech Science Foundation (project 16-14957Y) and by the Ministry of Education, Youth and Sports of the Czech Republic within the National Sustainability Program II (project BIOCEV-FAR LQ1604). NR 84 TC 0 Z9 0 U1 9 U2 9 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 OCT PY 2016 VL 27 IS 10 BP 2372 EP 2385 DI 10.1021/acs.bioconjchem.6b00370 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA DZ6SK UT WOS:000385992000019 PM 27583777 ER PT J AU Lesage, E Nailer, EL Miall, RC AF Lesage, Elise Nailer, Emma L. Miall, R. Chris TI Cerebellar BOLD signal during the acquisition of a new lexicon predicts its early consolidation SO BRAIN AND LANGUAGE LA English DT Article DE Cerebellum; Language; Vocabulary; Learning; Lexicon; fMRI; Word association; Non-motor ID WORKING-MEMORY; PREFRONTAL CORTEX; FUNCTIONAL TOPOGRAPHY; SEMANTIC KNOWLEDGE; EPISODIC MEMORY; INTERNAL-MODELS; COGNITIVE TASKS; HUMAN BRAIN; LANGUAGE; FMRI AB Cerebellar contributions to language are presently poorly understood, but it has been argued that the cerebellar role in motor learning can be extended to learning in cognitive and linguistic domains. Here, we used fMRI to investigate whether the cerebellum is recruited in mapping novel words onto existing semantic concepts. On separate days, participants performed a Basque vocabulary learning task and a control English synonym task in the MRI scanner. Learning-related BOLD activity was found in left inferior frontal gyrus, bilateral insula, pre-SMA, left superior parietal cortex, right caudate, the right cerebellar vermis and right cerebellar Crus II. The extent to which the cerebellar regions, but not the cerebral areas, were recruited during learning correlated positively with participants' off-line improvement in performance after the learning task. These data provide evidence for a cerebellar role in lexical learning, and suggest that the right cerebellum may contribute toward consolidation of lexico-semantic associations in the language network. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Lesage, Elise; Nailer, Emma L.; Miall, R. Chris] Univ Birmingham, Sch Psychol, Birmingham B15 2TT, W Midlands, England. [Lesage, Elise] NIDA, Neuroimaging Res Branch, NIH, Baltimore, MD 21224 USA. [Nailer, Emma L.] Univ Birmingham, Sch Educ, Birmingham B15 2TT, W Midlands, England. RP Lesage, E (reprint author), NIDA, Neuroimaging Res Branch, NIH, Baltimore, MD 21224 USA. EM Elise.r.d.lesage@gmail.com FU Wellcome Trust [WT087554]; Marie Curie Actions Grant [EU-FP7-ITN "C7"] FX This work was supported by grants from the Wellcome Trust (WT087554) and the Marie Curie Actions Grant EU-FP7-ITN "C7". We thank the staff of the Birmingham University Imaging Centre for their help. NR 97 TC 2 Z9 2 U1 2 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X EI 1090-2155 J9 BRAIN LANG JI Brain Lang. PD OCT PY 2016 VL 161 SI SI BP 33 EP 44 DI 10.1016/j.bandl.2015.07.005 PG 12 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA DZ8FA UT WOS:000386105100005 PM 26303580 ER PT J AU Thomas, RM Van Dyke, T Merlino, G Day, CP AF Thomas, Renee M. Van Dyke, Terry Merlino, Glenn Day, Chi-Ping TI Concepts in Cancer Modeling: A Brief History SO CANCER RESEARCH LA English DT Review ID ANTITUMOR IMMUNITY; MELANOMA; CHEMOTHERAPY; IMMUNOTHERAPY; KINETICS; THERAPY AB Modeling, an experimental approach to investigate complex biological systems, has significantly contributed to our understanding of cancer. Although extensive cancer research has been conducted utilizing animal models for elucidating mechanisms and developing therapeutics, the concepts in a good model design and its application have not been well elaborated. In this review, we discuss the theory underlying biological modeling and the process of producing a valuable and relevant animal model. Several renowned examples in the history of cancer research will be used to illustrate how modeling can be translatable to clinical applications. Finally, we will also discuss how the advances in cancer genomics and cancer modeling will influence each other going forward. (C) 2016 AACR. C1 [Thomas, Renee M.; Merlino, Glenn; Day, Chi-Ping] NCI, Lab Canc Biol & Genet, NIH, 37 Convent Dr,Room 5002, Bethesda, MD 20892 USA. [Thomas, Renee M.] NIH, Med Res Scholars Program, Bldg 10, Bethesda, MD 20892 USA. [Van Dyke, Terry] NCI, Ctr Adv Preclin Res, Ctr Canc Res, Frederick, MD 21701 USA. RP Merlino, G; Day, CP (reprint author), NCI, Lab Canc Biol & Genet, NIH, 37 Convent Dr,Room 5002, Bethesda, MD 20892 USA. EM gmerlino@helix.nih.gov; daychi@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999, ZIA BC011167-01] NR 26 TC 0 Z9 0 U1 4 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD OCT PY 2016 VL 76 IS 20 BP 5921 EP 5925 DI 10.1158/0008-5472.CAN-16-1293 PG 5 WC Oncology SC Oncology GA DZ1UW UT WOS:000385627600003 PM 27694601 ER PT J AU Campbell, PT Newton, CC Freedman, ND Koshiol, J Alavanja, MC Freeman, LEB Buring, JE Chan, AT Chong, DQ Datta, M Gaudet, MM Gaziano, JM Giovannucci, EL Graubard, BI Hollenbeck, AR King, L Lee, IM Linet, MS Palmer, JR Petrick, JL Poynter, JN Purdue, MP Robien, K Rosenberg, L Sahasrabuddhe, VV Schairer, C Sesso, HD Sigurdson, AJ Stevens, VL Wactawski-Wende, J Zeleniuch-Jacquotte, A Renehan, AG McGlynn, KA AF Campbell, Peter T. Newton, Christina C. Freedman, Neal D. Koshiol, Jill Alavanja, Michael C. Freeman, Laura E. Beane Buring, Julie E. Chan, Andrew T. Chong, Dawn Q. Datta, Mridul Gaudet, Mia M. Gaziano, J. Michael Giovannucci, Edward L. Graubard, Barry I. Hollenbeck, Albert R. King, Lindsey Lee, I-Min Linet, Martha S. Palmer, Julie R. Petrick, Jessica L. Poynter, Jenny N. Purdue, Mark P. Robien, Kim Rosenberg, Lynn Sahasrabuddhe, Vikrant V. Schairer, Catherine Sesso, Howard D. Sigurdson, Alice J. Stevens, Victoria L. Wactawski-Wende, Jean Zeleniuch-Jacquotte, Anne Renehan, Andrew G. McGlynn, Katherine A. TI Body Mass Index, Waist Circumference, Diabetes, and Risk of Liver Cancer for US Adults SO CANCER RESEARCH LA English DT Article ID EPIC-OXFORD PARTICIPANTS; BILIARY-TRACT CANCER; HEPATOCELLULAR-CARCINOMA; EUROPEAN COHORT; UNITED-STATES; MELLITUS; OBESITY; METAANALYSIS; ASSOCIATION; WEIGHT AB Incidence rates for liver cancer have increased 3-fold since the mid-1970s in the United States in parallel with increasing trends for obesity and type II diabetes mellitus. Weconducted an analysis of baseline body mass index (BMI), waist circumference (WC), and type II diabetes mellitus with risk of liver cancer. The Liver Cancer Pooling Project maintains harmonized data from 1.57 million adults enrolled in 14 U.S.-based prospective studies. Cox regression estimated HRs and 95% confidence intervals (CI) adjusted for age, sex, study center, alcohol, smoking, race, and BMI (for WC and type II diabetes mellitus). Stratified analyses assessed whether the BMI-liver cancer associations differed by hepatitis sera-positivity in nested analyses for a subset of cases (n = 220) and controls (n = 547). After enrollment, 2,162 incident liver cancer diagnoses were identified. BMI, per 5 kg/m(2), was associated with higher risks of liver cancer, more so for men (HR = 1.38; 95% CI, 1.30-1.46) than women (HR = 1.25; 95% CI, 1.17-1.35; P-interaction = 0.02). WC, per 5 cm, was associated with higher risks of liver cancer, approximately equally by sex (overall, HR = 1.08; 95% CI, 1.04-1.13). Type II diabetes mellitus was associated with higher risk of liver cancer (HR = 2.61; 95% CI, 2.34-2.91). In stratified analyses, there was a null association between BMI and liver cancer risk for participants who were sera-positive for hepatitis. This study suggests that high BMI, high WC, and type II diabetes mellitus are associated with higher risks of liver cancer and that the association may differ by status of viral hepatitis infection. (C) 2016 AACR. C1 [Campbell, Peter T.; Newton, Christina C.; Gaudet, Mia M.; Stevens, Victoria L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Freedman, Neal D.; Koshiol, Jill; Alavanja, Michael C.; Freeman, Laura E. Beane; Graubard, Barry I.; Linet, Martha S.; Petrick, Jessica L.; Purdue, Mark P.; Sahasrabuddhe, Vikrant V.; Schairer, Catherine; Sigurdson, Alice J.; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Buring, Julie E.; Chan, Andrew T.; Gaziano, J. Michael; King, Lindsey; Lee, I-Min; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Buring, Julie E.; Giovannucci, Edward L.; Lee, I-Min; Sesso, Howard D.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Chan, Andrew T.; King, Lindsey] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Chan, Andrew T.; Chong, Dawn Q.; King, Lindsey] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.; Chong, Dawn Q.; King, Lindsey] Harvard Med Sch, Boston, MA USA. [Chong, Dawn Q.] Natl Canc Ctr Singapore, Div Med Oncol, Singapore, Singapore. [Datta, Mridul] Purdue Univ, Dept Nutr Sci, W Lafayette, IN 47907 USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Boston, MA USA. [Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Hollenbeck, Albert R.] AARP, Washington, DC USA. [Palmer, Julie R.; Rosenberg, Lynn] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. [Poynter, Jenny N.] Univ Minnesota, Div Pediat Epidemiol & Clin Res, Minneapolis, MN USA. [Poynter, Jenny N.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [Robien, Kim] George Washington Univ, Milken Inst, Sch Publ Hlth, Dept Exercise & Nutr Sci, Washington, DC USA. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Epidemiol & Environm Hlth, Buffalo, NY USA. [Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Dept Populat Hlth, New York, NY USA. [Renehan, Andrew G.] Univ Manchester, Fac Inst Canc Sci, Manchester, Lancs, England. RP Campbell, PT (reprint author), Amer Canc Soc, 250 Williams St NW, Atlanta, GA 30303 USA. EM peter.campbell@cancer.org RI Beane Freeman, Laura/C-4468-2015; OI Beane Freeman, Laura/0000-0003-1294-4124; Robien, Kim/0000-0002-2120-2280; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303 FU Intramural NIH HHS [Z01 CP010119-12, Z01 ES049030-11]; NCI NIH HHS [UM1 CA186107, P01 CA055075, P01 CA087969, P30 CA016087, R01 CA034944, R01 CA034944-03, R01 CA039742, R01 CA040360, R01 CA047988, R01 CA049449, R01 CA058420, R01 CA097193, R01 CA098661, UM1 CA164974, UM1 CA167552]; NHLBI NIH HHS [R01 HL026490, R01 HL026490-03, R01 HL034595, R01 HL034595-07, R01 HL043851, R01 HL080467]; NIEHS NIH HHS [P30 ES000260, Z01 ES049030] NR 37 TC 0 Z9 0 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD OCT PY 2016 VL 76 IS 20 BP 6076 EP 6083 DI 10.1158/0008-5472.CAN-16-0787 PG 8 WC Oncology SC Oncology GA DZ1UW UT WOS:000385627600018 PM 27742674 ER PT J AU Ali, I Hogberg, J Hsieh, JH Auerbach, S Korhonen, A Stenius, U Silins, I AF Ali, Imran Hogberg, Johan Hsieh, Jui-Hua Auerbach, Scott Korhonen, Anna Stenius, Ulla Silins, Ilona TI Gender differences in cancer susceptibility: role of oxidative stress SO CARCINOGENESIS LA English DT Article ID HEME OXYGENASE-1; SEX DISPARITIES; CHROMOSOME Y; MOSAIC LOSS; CARCINOGENESIS; RISK AB Cancer statistics indicate that compared to women, men are more susceptible to cancer. In literature analysis based on about 600000 scientific references covering male- and female-specific carcinogens, estradiol and testosterone, oxidative stress emerges as one critical factor that could offer explanation for the gender disparity observed.Cancer is a leading cause of death worldwide and environmental factors, including chemicals, have been suggested as major etiological incitements. Cancer statistics indicates that men get more cancer than women. However, differences in the known risk factors including life style or occupational exposure only offer partial explanation. Using a text mining tool, we have investigated the scientific literature concerning male- and female-specific rat carcinogens that induced tumors only in one gender in NTP 2-year cancer bioassay. Our evaluation shows that oxidative stress, although frequently reported for both male- and female-specific rat carcinogens, was mentioned significantly more in literature concerning male-specific rat carcinogens. Literature analysis of testosterone and estradiol showed the same pattern. Tox21 high-throughput assay results, although showing only weak association of oxidative stress-related processes for male- and female-specific rat carcinogens, provide additional support. We also analyzed the literature concerning 26 established human carcinogens (IARC group 1). Oxidative stress was more frequently reported for the majority of these carcinogens, and the Tox21 data resembled that of male-specific rat carcinogens. Thus, our data, based on about 600000 scientific abstracts and Tox21 screening assays, suggest a link between male-specific carcinogens, testosterone and oxidative stress. This implies that a different cellular response to oxidative stress in men and women may be a critical factor in explaining the greater cancer susceptibility observed in men. Although the IARC carcinogens are classified as human carcinogens, their classification largely based on epidemiological evidence from male cohorts, which raises the question whether carcinogen classifications should be gender specific. C1 [Ali, Imran; Hogberg, Johan; Stenius, Ulla; Silins, Ilona] Karolinska Inst, Inst Environm Med, SE-17177 Stockholm, Sweden. [Hsieh, Jui-Hua; Auerbach, Scott] NIEHS, Div Natl Toxicol Program, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. [Korhonen, Anna] Univ Cambridge, Dept Theoret & Appl Linguist, Cambridge CB3 9DA, England. RP Ali, I; Silins, I (reprint author), Karolinska Inst, Inst Environm Med, SE-17177 Stockholm, Sweden. EM imran.ali@ki.se; ilona.silins@ki.se OI Ali, Imran/0000-0001-9274-2295 FU Swedish Research Council Formas [2013-0529]; Swedish Research Council for Health, Working Life and Welfare (FORTE) [2014-1530]; VINNOVA, Sweden [2011-01319] FX This work was supported by The Swedish Research Council Formas (Grant number 2013-0529), Swedish Research Council for Health, Working Life and Welfare (FORTE) (grant number 2014-1530) and VINNOVA (grant number 2011-01319), Sweden. NR 35 TC 0 Z9 0 U1 1 U2 1 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 OCT PY 2016 VL 37 IS 10 BP 985 EP 992 DI 10.1093/carcin/bgw076 PG 8 WC Oncology SC Oncology GA DZ7IC UT WOS:000386037100008 PM 27481070 ER PT J AU Callejas-Valera, JL Iglesias-Bartolome, R Amornphimoltham, P Palacios-Garcia, J Martin, D Califano, JA Molinolo, AA Gutkind, JS AF Callejas-Valera, Juan Luis Iglesias-Bartolome, Ramiro Amornphimoltham, Panomwat Palacios-Garcia, Julia Martin, Daniel Califano, Joseph A. Molinolo, Alfredo A. Gutkind, J. Silvio TI mTOR inhibition prevents rapid-onset of carcinogen-induced malignancies in a novel inducible HPV-16 E6/E7 mouse model SO CARCINOGENESIS LA English DT Article ID HUMAN-PAPILLOMAVIRUS TYPE-16; SQUAMOUS-CELL CARCINOMA; STEM-CELLS; OROPHARYNGEAL CANCER; HAIR FOLLICLE; TUMOR-GROWTH; HPV16 E6/E7; SKIN; E7; E6 AB The rising incidence of human papillomavirus (HPV)-associated malignancies, especially for oropharyngeal cancers, has highlighted the urgent need to understand how the interplay between high-risk HPV oncogenes and carcinogenic exposure results in squamous cell carcinoma (SCC) development. Here, we describe an inducible mouse model expressing high risk HPV-16 E6/E7 oncoproteins in adults, bypassing the impact of these viral genes during development. HPV-16 E6/E7 genes were targeted to the basal squamous epithelia in transgenic mice using a doxycycline inducible cytokeratin 5 promoter (cK5-rtTA) system. After doxycycline induction, both E6 and E7 were highly expressed, resulting in rapid epidermal hyperplasia with a remarkable expansion of the proliferative cell compartment to the suprabasal layers. Surprisingly, in spite of the massive growth of epithelial cells and their stem cell progenitors, HPV-E6/E7 expression was not sufficient to trigger mTOR activation, a key oncogenic driver in HPV-associated malignancies, and malignant progression to SCC. However, these mice develop SCC rapidly after a single exposure to a skin carcinogen, DMBA, which was increased by the prolonged exposure to a tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Thus, only few oncogenic hits may be sufficient to induce cancer in E6/E7 expressing cells. All HPV-E6/E7 expressing SCC lesions exhibited increased mTOR activation. Remarkably, rapamycin, an mTOR inhibitor, abolished tumor development when administered to HPV-E6/E7 mice prior to DMBA exposure. Our findings revealed that mTOR inhibition protects HPV-E6/E7 expressing tissues form SCC development upon carcinogen exposure, thus supporting the potential clinical use of mTOR inhibitors as a molecular targeted approach for prevention of HPV-associated malignancies. C1 [Callejas-Valera, Juan Luis; Amornphimoltham, Panomwat; Califano, Joseph A.; Molinolo, Alfredo A.; Gutkind, J. Silvio] Moores Canc Ctr, 3855 Hlth Sci Dr, La Jolla, CA 92093 USA. [Iglesias-Bartolome, Ramiro] NIAMS, Dev Skin Biol Sect HNB 254, NIH, Bldg 50, Bethesda, MD 20814 USA. [Palacios-Garcia, Julia] Ctr Biol Mol Severo Ochoa CSIC UAM, Madrid 28049, Spain. [Martin, Daniel] NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bldg 30, Bethesda, MD 20892 USA. RP Gutkind, JS (reprint author), Moores Canc Ctr, 3855 Hlth Sci Dr, La Jolla, CA 92093 USA. EM sgutkind@ucsd.edu NR 47 TC 0 Z9 0 U1 1 U2 1 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 OCT PY 2016 VL 37 IS 10 BP 1014 EP 1025 DI 10.1093/carcin/bgw086 PG 97 WC Oncology SC Oncology GA DZ7IC UT WOS:000386037100001 PM 27538837 ER PT J AU Zhang, T Ye, YH AF Zhang, Ting Ye, Yihong TI Ever HRD a ubiquitin-gated channel? SO CELL RESEARCH LA English DT Editorial Material ID ENDOPLASMIC-RETICULUM; QUALITY-CONTROL; ER PROTEINS; RETROTRANSLOCATION AB Elimination of misfolded proteins of the endoplasmic reticulum (ER) requires their retrotranslocation from the ER to the cytosol via membrane-bound ubiquitin ligase complexes. Baldridge and Rapoport now reconstitute a key step of retrotranslocation, demonstrating a protein conduit gated by ubiquitination. C1 [Zhang, Ting; Ye, Yihong] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Ye, YH (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM yihongy@mail.nih.gov NR 10 TC 0 Z9 0 U1 3 U2 3 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 EI 1748-7838 J9 CELL RES JI Cell Res. PD OCT PY 2016 VL 26 IS 10 BP 1075 EP 1076 DI 10.1038/cr.2016.92 PG 2 WC Cell Biology SC Cell Biology GA DZ8QF UT WOS:000386135200003 PM 27491350 ER PT J AU Kadri, SS Rhee, C Magda, G Strich, JR Cai, RM Sun, JF Decker, BK O'Grady, NP AF Kadri, Sameer S. Rhee, Chanu Magda, Gabriela Strich, Jeffrey R. Cai, Rongman Sun, Junfeng Decker, Brooke K. O'Grady, Naomi P. TI Synergy, Salary, and Satisfaction: Benefits of Training in Critical Care Medicine and Infectious Diseases Gleaned From a National Pilot Survey of Dually Trained Physicians SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE critical care; infectious diseases; survey ID UNITED-STATES; EMERGENCY PHYSICIANS; MORTALITY; CONSULTATIONS; SUBSPECIALTY; CHALLENGES; PREVENTION; PULMONARY; EDUCATION; THERAPY AB A survey of physicians trained in critical care medicine (CCM) and infectious diseases (ID) suggested this combination is synergistic and satisfying. However, most respondents had to train in individual specialties at separate institutions. Avenues for CCM-ID training should be considered.Methods.aEuro integral All physicians trained and/or certified in both CCM and ID to date in the United States were sent a Web-based questionnaire in 2015. Responses enabled a cross-sectional analysis of physician demographics and training and practice characteristics and satisfaction. Results.aEuro integral Of 202 CCM-ID physicians, 196 were alive and reachable. The response rate was 79%. Forty-six percent trained and 34% practice in the northeastern United States. Only 40% received dual training at the same institution. Eighty-three percent identified as either an intensivist with ID expertise (44%) or as equally an intensivist and ID physician (38%). Median salary was $265 000 (interquartile range [IQR], $215 000-$350 000). Practice settings were split between academic (45%) and community settings (42%). Two-thirds are clinicians but 62% conduct some research and 26% practice outpatient ID. Top reasons to dually specialize included clinical synergy (70%), procedural activity (50%), and less interest in pulmonology (49%). Although 38% cited less proficiency with bronchoscopy as a disadvantage, 87% seldom need pulmonary consultation in the intensive care unit. Median career satisfaction was 4 (IQR, 4-5) out of 5, and 76% would dually train again. Conclusions.aEuro integral CCM-ID graduates prefer the acute care setting, predominantly CCM or a combination of CCM and ID. They find combination training and practice to be synergistic and satisfying, but most have had to seek CCM and ID training independently at separate institutions. Given these findings, avenues for combined training in CCM-ID should be considered. C1 [Kadri, Sameer S.; Cai, Rongman; Sun, Junfeng; O'Grady, Naomi P.] NIH, Dept Crit Care Med, Ctr Clin, 10 Ctr Dr,B10 2C-145, Bethesda, MD 20892 USA. [Rhee, Chanu] Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA. [Rhee, Chanu] Harvard Med Sch, Dept Populat Med, Boston, MA USA. [Rhee, Chanu] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Magda, Gabriela] Georgetown Univ Hosp, Medstar, Dept Med, Washington, DC 20007 USA. [Strich, Jeffrey R.] NIAID, Div Clin Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Decker, Brooke K.] VA Pittsburgh Healthcare Syst, Infect Dis Sect, Pittsburgh, PA USA. RP Kadri, SS (reprint author), NIH, Dept Crit Care Med, Ctr Clin, 10 Ctr Dr,B10 2C-145, Bethesda, MD 20892 USA. EM sameer.kadri@nih.gov FU National Institutes of Health FX This work was supported by intramural funds from the National Institutes of Health. NR 34 TC 3 Z9 3 U1 1 U2 1 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 OCT 1 PY 2016 VL 63 IS 7 BP 868 EP 875 DI 10.1093/cid/ciw441 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DZ7JL UT WOS:000386041100009 PM 27358351 ER PT J AU Fwu, CW Kimmel, PL Eggers, PW Abbott, KC AF Fwu, Chyng-Wen Kimmel, Paul L. Eggers, Paul W. Abbott, Kevin C. TI Comparison of trends in colorectal cancer screening in the US end-stage renal disease population and the US Medicare population SO CLINICAL KIDNEY JOURNAL LA English DT Article DE colorectal cancer; dialysis; screening; kidney; transplant; USRDS ID TRANSPLANT CANDIDATES; KIDNEY-TRANSPLANT; DIALYSIS PATIENTS; GUIDELINES; RISK; HEMODIALYSIS; COLONOSCOPY; BENEFITS; SOCIETY; INJURY AB Background: Although patients treated with maintenance hemodialysis are at an increased risk of colorectal cancer compared with the general population, national practices for colorectal cancer screening have not been reported in this population. We assessed the performance of colorectal cancer screening in the US end-stage renal disease program in comparison with the US Medicare population. Methods: We studied the United States Renal Data System for US prevalent hemodialysis patients between 2002 and 2011 who had Medicare as their primary insurer. We assessed procedure codes for performance of common colorectal cancer screening tests, including fecal occult blood testing, sigmoidoscopy and colonoscopy. We assessed screening sigmoidoscopy and screening colonoscopy only and excluded patients who had preexisting colon cancer or gastrointestinal hemorrhage. Because colorectal cancer screening recommendations are established for hemodialysis patients who have been listed for kidney transplantation, but no general recommendations exist for patients who are not wait-listed, we assessed colorectal cancer screening separately for the two groups. Results: We found that 1-year performance of colonoscopy in wait-listed hemodialysis patients was similar to or higher than that in general Medicare patients of the same age, while performance of colonoscopy in non-wait-listed patients was significantly lower than among general Medicare patients of the same age. Conclusions: Given improved survival among hemodialysis patients in the last decade, the utility of colorectal cancer screening even among non-wait-listed hemodialysis patients should be reassessed. C1 [Fwu, Chyng-Wen] Social & Sci Syst Inc, Silver Spring, MD USA. [Kimmel, Paul L.; Eggers, Paul W.; Abbott, Kevin C.] NIDDK, Div Kidney Urol & Hematol Dis, NIH, 6707 Democracy Blvd, Bethesda, MD 20892 USA. RP Abbott, KC (reprint author), NIDDK, Div Kidney Urol & Hematol Dis, NIH, 6707 Democracy Blvd, Bethesda, MD 20892 USA. EM kevin.abbott@nih.gov OI Abbott, Kevin/0000-0003-2111-7112 NR 28 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1753-0784 EI 1753-0792 J9 CLIN KIDNEY J JI Clin. Kidney J. PD OCT PY 2016 VL 9 IS 5 BP 722 EP 728 DI 10.1093/ckj/sfw053 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA DZ8OX UT WOS:000386131400011 PM 27679719 ER PT J AU Yamada, KM Mayor, R AF Yamada, Kenneth M. Mayor, Roberto TI Editorial overview: Cell dynamics in development, tissue remodelling, and cancer SO CURRENT OPINION IN CELL BIOLOGY LA English DT Editorial Material C1 [Yamada, Kenneth M.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, Cell Biol Sect, NIH, Bethesda, MD 20892 USA. [Mayor, Roberto] UCL, Dept Cell & Dev Biol, Gower St, London WC1E 6BT, England. RP Yamada, KM (reprint author), Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, Cell Biol Sect, NIH, Bethesda, MD 20892 USA. EM kyamada@dir.nidcr.nih.gov; r.mayor@ucl.ac.uk NR 0 TC 0 Z9 0 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 EI 1879-0410 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD OCT PY 2016 VL 42 BP IV EP VI DI 10.1016/j.ceb.2016.09.001 PG 3 WC Cell Biology SC Cell Biology GA EA1PC UT WOS:000386363300001 PM 27725095 ER PT J AU Petrie, RJ Yamada, KM AF Petrie, Ryan J. Yamada, Kenneth M. TI Multiple mechanisms of 3D migration: the origins of plasticity SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID 3-DIMENSIONAL CELL-MIGRATION; FUNDULUS DEEP CELLS; LEADING-EDGE; FOCAL ADHESIONS; RAC ACTIVATION; STRESS FIBERS; CONTRACTILITY; MATRIX; INVASION; DYNAMICS AB Cells migrate through 3D environments using a surprisingly wide variety of molecular mechanisms. These distinct modes of migration often rely on the same intracellular components, which are used in different ways to achieve cell motility. Recent work reveals that how a cell moves can be dictated by the relative amounts of cell-matrix adhesion and actomyosin contractility. A current concept is that the level of difficulty in squeezing the nucleus through a confining 3D environment determines the amounts of adhesion and contractility required for cell motility. Ultimately, determining how the nucleus controls the mode of cell migration will be essential for understanding both physiological and pathological processes dependent on cell migration in the body. C1 [Petrie, Ryan J.] Drexel Univ, Dept Biol, Philadelphia, PA 19104 USA. [Yamada, Kenneth M.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD USA. RP Petrie, RJ (reprint author), Drexel Univ, Dept Biol, Philadelphia, PA 19104 USA. EM rjp336@drexel.edu FU Department of Biology; College of Arts and Sciences of Drexel University; National Institutes of Health, National Institute of Dental and Craniofacial Research (NIH, NIDCR) FX RJP is supported by startup funds from the Department of Biology and the College of Arts and Sciences of Drexel University. Work in KMY's laboratory is supported by the Intramural Research Program of the National Institutes of Health, National Institute of Dental and Craniofacial Research (NIH, NIDCR). NR 64 TC 4 Z9 4 U1 8 U2 8 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 EI 1879-0410 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD OCT PY 2016 VL 42 BP 7 EP 12 DI 10.1016/j.ceb.2016.03.025 PG 6 WC Cell Biology SC Cell Biology GA EA1PC UT WOS:000386363300003 PM 27082869 ER PT J AU Koo, H Yamada, KM AF Koo, Hyun Yamada, Kenneth M. TI Dynamic cell-matrix interactions modulate microbial biofilm and tissue 3D microenvironments SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID VIBRIO-CHOLERAE BIOFILMS; EXTRACELLULAR-MATRIX; STREPTOCOCCUS-MUTANS; BACILLUS-SUBTILIS; PSEUDOMONAS-AERUGINOSA; CANDIDA-ALBICANS; IN-VIVO; STIFFNESS; CANCER; COLLAGEN AB Microbial biofilms and most eukaryotic tissues consist of cells embedded in a three-dimensional extracellular matrix. This matrix serves as a scaffold for cell adhesion and a dynamic milieu that provides varying chemical and physical signals to the cells. Besides a vast array of specific molecular components, an extracellular matrix can provide locally heterogeneous microenvironments differing in porosity/diffusion, stiffness, pH, oxygen and metabolites or nutrient levels. Mechanisms of matrix formation, mechanosensing, matrix remodeling, and modulation of cell-cell or cell-matrix interactions and dispersal are being revealed. This perspective article aims to identify such concepts from the fields of biofilm or eukaryotic matrix biology relevant to the other field to help stimulate new questions, approaches, and insights. C1 [Koo, Hyun] Univ Penn, Sch Dent Med, Dept Orthodont, Biofilm Res Labs,Levy Ctr Oral Hlth, Philadelphia, PA 19104 USA. [Koo, Hyun] Univ Penn, Sch Dent Med, Div Pediat Dent, Philadelphia, PA 19104 USA. [Koo, Hyun] Univ Penn, Sch Dent Med, Div Community Oral Hlth, Philadelphia, PA 19104 USA. [Yamada, Kenneth M.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, Cell Biol Sect, NIH, Bethesda, MD 20892 USA. [Koo, Hyun] Univ Penn, Sch Dent Med, 240 South 40th St,Levy Bldg Rm 417, Philadelphia, PA 19104 USA. RP Koo, H (reprint author), Univ Penn, Sch Dent Med, 240 South 40th St,Levy Bldg Rm 417, Philadelphia, PA 19104 USA. EM koohy@upenn.edu FU National Institute for Dental and Craniofacial Research (NIDCR), NIH Intramural Research Program; NIDCR [DE16139, DE18023, DE25220] FX The authors' research is supported by the National Institute for Dental and Craniofacial Research (NIDCR), NIH Intramural Research Program (KMY) and by NIDCR grants DE16139, DE18023, and DE25220 (HK). We thank Dr. Marlise Klein (State University of Sao Paulo, Brazil) and Dr. William H. Bowen (University of Rochester Medical Center, Rochester, NY, USA) for helpful suggestions and comments. We are also grateful to Jill Harunaga, Ryan Petrie, and Roumen Pankov for the fluorescence images. The diagrams and schematics were designed by Long Do and Mirae Jang (The University of Arts, Philadelphia, PA, USA; Instructor: Joel Katz). The authors regret that many studies could only be cited indirectly owing to space and reference number limitation. NR 71 TC 1 Z9 1 U1 6 U2 6 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 EI 1879-0410 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD OCT PY 2016 VL 42 BP 102 EP 112 DI 10.1016/j.ceb.2016.05.005 PG 11 WC Cell Biology SC Cell Biology GA EA1PC UT WOS:000386363300014 PM 27257751 ER PT J AU Deroo, LA Wilcox, AJ Lie, RT Romitti, PA Pedersen, DA Munger, RG Uribe, LMM Wehby, GL AF DeRoo, Lisa A. Wilcox, Allen J. Lie, Rolv T. Romitti, Paul A. Pedersen, Dorthe Almind Munger, Ronald G. Uribe, Lina M. Moreno Wehby, George L. TI Maternal alcohol binge-drinking in the first trimester and the risk of orofacial clefts in offspring: a large population-based pooling study SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Cleft lip; Cleft palate; Alcohol ID BIRTH-DEFECTS; ORAL CLEFTS; POOLED ANALYSES; CONSUMPTION; PREGNANCY; METAANALYSES; EPIDEMIOLOGY; NORWAY; COHORT; GENES AB Using individual participant data from six population-based case-control studies, we conducted pooled analyses to examine maternal alcohol consumption and the risk of clefts among > 4600 infants with cleft lip only, cleft lip with cleft palate, or cleft palate only and > 10,000 unaffected controls. We examined two first-trimester alcohol measures: average number of drinks/sitting and maximum number of drinks/sitting, with five studies contributing to each analysis. Study-specific odds ratios (ORs) were estimated using logistic regression and pooled to generate adjusted summary ORs. Across studies, 0.9-3.2 % of control mothers reported drinking an average of 5+ drinks/sitting, while 1.4-23.5 % reported drinking a maximum of 5+ drinks/sitting. Compared with non-drinkers, mothers who drank an average of 5+ drinks/sitting were more likely to deliver an infant with cleft lip only (pooled OR 1.48; 95 % confidence intervals 1.01, 2.18). The estimate was higher among women who drank at this level 3+ times (pooled OR 1.95; 1.23, 3.11). Ever drinking a maximum of 5+ drinks/sitting and non-binge drinking were not associated with cleft risk. Repeated heavy maternal alcohol consumption was associated with an increased risk of cleft lip only in offspring. There was little evidence of increased risk for other cleft types or alcohol measures. C1 [DeRoo, Lisa A.; Lie, Rolv T.] Univ Bergen, Dept Global Publ Hlth & Primary Care, Postboks 7804, N-5020 Bergen, Norway. [DeRoo, Lisa A.; Wilcox, Allen J.] NIEHS, Epidemiol Branch, NIH, Durham, NC 27711 USA. [Lie, Rolv T.] Med Birth Registry Norway, Norwegian Inst Publ Hlth, Bergen, Norway. [Romitti, Paul A.] Univ Iowa, Dept Epidemiol, Coll Publ Hlth, Iowa City, IA USA. [Pedersen, Dorthe Almind] Univ Southern Denmark, Inst Publ Hlth, Epidemiol Biostat & Biodemog, Odense, Denmark. [Munger, Ronald G.] Utah State Univ, Dept Nutr Dietet & Food Sci, Logan, UT 84322 USA. [Uribe, Lina M. Moreno] Univ Iowa, Dept Orthodont, Coll Dent & Dent Clin, Iowa City, IA USA. [Wehby, George L.] Univ Iowa, Dept Hlth Management & Policy, 105 River St, Iowa City, IA 52242 USA. RP Deroo, LA (reprint author), Univ Bergen, Dept Global Publ Hlth & Primary Care, Postboks 7804, N-5020 Bergen, Norway.; Deroo, LA (reprint author), NIEHS, Epidemiol Branch, NIH, Durham, NC 27711 USA.; Wehby, GL (reprint author), Univ Iowa, Dept Hlth Management & Policy, 105 River St, Iowa City, IA 52242 USA. EM Lisa.De.Roo@igs.uib.no; george-wehby@uiowa.edu OI Wilcox, Allen/0000-0002-3376-1311 FU National Institutes of Health (NIH), National Institute of Dental and Craniofacial Research (NIDCR) [1 R01 DE020895]; Intramural Research Program of the National Institute of Environmental Health Sciences (NIEHS) [ZIA-ES-49027]; NIH [R01 HD39061]; U.S. Centers for Disease Control and Prevention (CDC) [U01-DD000492, U01-D000698, U01-DD001035]; Norwegian Ministry of Health; Ministry of Education and Research FX The main funding for this study was provided by Grant 1 R01 DE020895 from the National Institutes of Health (NIH), National Institute of Dental and Craniofacial Research (NIDCR). This research was also supported in part by the Intramural Research Program of the National Institute of Environmental Health Sciences (NIEHS) (ZIA-ES-49027). Additional partial funding was from NIH grant R01 HD39061, U.S. Centers for Disease Control and Prevention (CDC) grants U01-DD000492, U01-D000698, and U01-DD001035, and the Norwegian Ministry of Health and the Ministry of Education and Research. We thank Drs. Abee L. Boyles, Lorenzo D. Botto, Sonja A. Rasmussen and Donna D. Baird and for helpful comments on an earlier draft of this manuscript. NR 35 TC 1 Z9 1 U1 4 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0393-2990 EI 1573-7284 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PD OCT PY 2016 VL 31 IS 10 BP 1021 EP 1034 DI 10.1007/s10654-016-0171-5 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA EA1SP UT WOS:000386372500006 PM 27350158 ER PT J AU Chiang, YJ Hodes, RJ AF Chiang, Y. Jeffrey Hodes, Richard J. TI T-cell development is regulated by the coordinated function of proximal and distal Lck promoters active at different developmental stages SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Development; T cell; Thymus; Lck; Promoter ID MAMMALIAN GENOMES; EXPRESSION; P56(LCK); THYMOCYTES; DISSECTION; ACTIVATION; GENE AB Expression of Lck, a T-cell lineage-specific tyrosine kinase critical for T-cell development and activation, can be mediated by either proximal or distal lck promoter. We generated BAC transgenic mice in which BAC lck promoter was deleted and bred these transgenes to an Lck knockout background. Lck-PROX mice, in which only the proximal promoter is functional, have maximal Lck protein and normal thymic development through CD4(-)CD8(-) double negative (DN) and CD4(+)CD8(+) double positive (DP) stages, but undetectable Lck later in development and reduced mature single positive thymocytes. In contrast, Lck-DIST mice, in which only distal promoter was functional, are deficient in Lck protein in DN and DP thymocytes and severely defective in early T-cell development, with a block at the DN3-DN4 beta checkpoint equivalent to complete Lck knockouts. The ability of the proximal lck promoter to support thymic development is independent of Fyn; while, in contrast, the distal lck promoter alone is completely unable to support development in the absence of Fyn. Notably, normal thymocyte development is restored by presence of both proximal and distal promoters, even when independently expressed on different lck genes. These results define distinct and complementary requirements for proximal and distal lck promoters during T-cell development. C1 [Chiang, Y. Jeffrey; Hodes, Richard J.] NCI, Expt Immunol Branch, Bldg 10, Bethesda, MD 20892 USA. [Hodes, Richard J.] NIA, NIH, Bethesda, MD 20892 USA. RP Hodes, RJ (reprint author), NCI, Expt Immunol Branch, Bldg 10, Bethesda, MD 20892 USA.; Hodes, RJ (reprint author), NIA, NIH, Bethesda, MD 20892 USA. EM hodesr@31.nia.nih.gov FU National Institutes of Health, National Cancer Institute FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 20 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 2016 VL 46 IS 10 BP 2401 EP 2408 DI 10.1002/eji.201646440 PG 8 WC Immunology SC Immunology GA DZ9VV UT WOS:000386229600013 PM 27469439 ER PT J AU Tikkanen, R Saukkonen, T Fex, M Bennet, H Rautiainen, MR Paunio, T Koskinen, M Panarsky, R Bevilacqua, L Sjoberg, RL Tiihonen, J Virkkunen, M AF Tikkanen, R. Saukkonen, T. Fex, M. Bennet, H. Rautiainen, M. -R. Paunio, T. Koskinen, M. Panarsky, R. Bevilacqua, L. Sjoberg, R. L. Tiihonen, J. Virkkunen, M. TI Influence of a HTR2B Stop Codon on Glucagon Homeostasis and Glucose Excursion in Non-Diabetic Men SO EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES LA English DT Article DE glucose; glucagon; serotonin 2B receptor; oral glucose tolerance test; insulin resistance; BMI ID INSULIN-SECRETION; GLYCOGEN-SYNTHESIS; SEROTONIN; PHOSPHORYLASE; DYSREGULATION; HYPERGLYCEMIA; METABOLISM; ACTIVATION; MECHANISMS; RATS AB Limited data are available about the role of the serotonin 2B (5-HT2B) receptor in the function of human islets. This study aimed to test whether the 5-HT2B receptor contributes to glucose, insulin, and glucagon homeostasis in humans, utilizing a hereditary loss-of-function gene mutation in the receptor, which causes a 50% reduction in the production of the receptor protein in heterozygotes. This clinical study enrolled participants recruited by newspaper advertisements and from mental status examinations. A cohort of participants from a young Finnish founder population composed of 68 non-diabetic males with a mean age of 30 was divided into groups for comparison based on being a 5-HT2B receptor loss-of-function gene mutation (HTR2B Q20*) heterozygote carrier (n=11) or not (n=57). Serum levels of glucose, insulin, and glucagon were measured in a 5h oral glucose tolerance test using a 75g glucose challenge. Insulin resistance, insulin sensitivity, and beta cell activity were calculated using the homeostasis model assessment (HOMA2) and whole body insulin sensitivity index (WBISI), as well as the ratio of glucagon to insulin was noted. The areas under the curves (AUCs) were also determined. Concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured in cerebrospinal fluid (CSF). Covariate adjusted mean score comparisons were applied. Lower glucagon secretion and decreased glucose excursion were observed among HTR2B Q20* carriers as compared with individuals who were homozygotes for the wild-type Q20 allele (controls). No differences in insulin secretion, beta cell activity, insulin resistance, or insulin sensitivity were observed. The glucagon to insulin ratio differed between the HTR2B Q20* carriers and controls. CSF levels of 5-HIAA were similar between groups. Our findings indicate that the 5-HT2B receptor may contribute to the regulation of human glucagon and glucose homeostasis and the interplay between glucagon and insulin secretion. C1 [Tikkanen, R.; Paunio, T.; Virkkunen, M.] Univ Helsinki, Dept Psychiat, Cent Hosp, Helsinki, Finland. [Tikkanen, R.] Rinnekoti Fdn, Res & Dev, Espoo, Finland. [Saukkonen, T.] Univ Helsinki, Cent Hosp, Childrens Hosp, Helsinki, Finland. [Saukkonen, T.] Univ Helsinki, Helsinki, Finland. [Saukkonen, T.] Novo Nordisk Farma Oy, Espoo, Finland. [Fex, M.; Bennet, H.] Lund Univ, Ctr Diabet, Scania Univ Hosp, Dept Clin Sci, Malmo, Sweden. [Rautiainen, M. -R.; Paunio, T.; Tiihonen, J.] Natl Inst Hlth & Welf, Helsinki, Finland. [Koskinen, M.] Oy Aava Dev Ltd, Helsinki, Finland. [Panarsky, R.] NIAAA, Neurogenet Lab, Bethesda, MD USA. [Bevilacqua, L.] NYU, Sch Med, Dept Psychiat, New York, NY USA. [Sjoberg, R. L.; Tiihonen, J.] Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden. [Tiihonen, J.] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. [Tiihonen, J.] Univ Eastern Finland, Niuvanniemi Hosp, Dept Forens Psychiat, Kuopio, Finland. RP Tikkanen, R (reprint author), Univ Helsinki, Dept Psychiat, Valskarinkatu 12,POB 22, Helsinki 00260, Finland. EM roope.tikkanen@gmail.com FU Orion Research Foundation; Swedish Research Council [2012-1552]; Waldemar von Frenckell Foundation FX We thank for receiving the following grants: the Orion Research Foundation (R.T), Swedish Research Council (project number: 2012-1552 to M.F), and Waldemar von Frenckell Foundation (MR.R). Excellence in diabetes research (EXODIAB), Krapperup foundation, Ake Wiberg foundation, Royal Physiographic Society, Albert Pahlsson foundation, Crafoord foundation, Childhood Diabetes Foundation, and the Foundation of Sigurd and Elsa Golijes Minne. NR 30 TC 0 Z9 0 U1 0 U2 0 PU JOHANN AMBROSIUS BARTH VERLAG MEDIZINVERLAGE HEIDELBERG GMBH PI STUTTGART PA RUEDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0947-7349 EI 1439-3646 J9 EXP CLIN ENDOCR DIAB JI Exp. Clin. Endocrinol. Diabet. PD OCT PY 2016 VL 124 IS 9 BP 529 EP 534 DI 10.1055/s-0042-109263 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EA0XR UT WOS:000386313300002 PM 27437919 ER PT J AU Mookherjee, S Banerjee, D Chakraborty, S Mukhopadhyay, I Sen, A Ray, K AF Mookherjee, Suddhasil Banerjee, Deblina Chakraborty, Subhadip Mukhopadhyay, Indranil Sen, Abhijit Ray, Kunal TI Evaluation of the IL1 Gene Cluster Single Nucleotide Polymorphisms in Primary Open-Angle Glaucoma Pathogenesis SO GENETIC TESTING AND MOLECULAR BIOMARKERS LA English DT Article DE genetics; glaucoma; POAG; interleukins; association study ID HEAT-SHOCK PROTEINS; AQUEOUS-HUMOR; IL-1F7 GENE; ASSOCIATION; IDENTIFICATION; POPULATION; IMMUNITY; DISEASE AB Aims: Dysregulation of the immune system has previously been implicated in glaucoma pathogenesis. In this study, we investigated the potential association of SNPs in the IL1 gene cluster, consisting of nine genes, with primary open-angle glaucoma (POAG) cases. These cases presented with low to normal intraocular pressures (<20mmHg), and are referred to as non-high tension glaucoma (non-HTG) cases. Materials and Methods: In this biphasic study, the discovery phase was conducted with 198 non-HTG cases and 112 controls from eastern India. A total of 68 single nucleotide polymorphisms (SNPs) spanning the IL1 nine-gene cluster region were genotyped using the MALDI-TOF based Sequenom platform. SNPs, which were found to be significantly associated with non-HTG cases in the first phase of the study, were further genotyped by Sanger sequencing in a replication cohort consisting of 194 non-HTG cases and 242 controls. Results: In the discovery phase, two nonsynonymous SNPs (rs3811046 and rs3811047), located in the IL1F7 gene and in an intergenic region, respectively were found to be weakly associated with non-HTG cases. However, the association was not sustained in the replication cohort. Conclusion: Our study did not reveal any reproducible association of SNPs in the IL1 gene cluster with POAG. C1 [Mookherjee, Suddhasil; Banerjee, Deblina; Chakraborty, Subhadip; Ray, Kunal] CSIR Indian Inst Chem Biol, Mol & Human Genet Div, Kolkata, India. [Mukhopadhyay, Indranil] Indian Stat Inst, Human Genet Unit, Kolkata, India. [Sen, Abhijit] Dristi Pradip, Kolkata, India. [Mookherjee, Suddhasil] NEI, NIH, 6 Ctr Dr, Bethesda, MD 20892 USA. [Banerjee, Deblina] NCI, NIH, Bethesda, MD 20892 USA. [Chakraborty, Subhadip] Univ Calcutta, SN Pradhan Ctr Neurosci, Kolkata, India. [Ray, Kunal] CSIR Cent Rd Res Inst, Acad Sci & Innovat Res, CRRI PO Delhi,Mathura Rd, New Delhi 110025, India. RP Mookherjee, S (reprint author), NEI, NIH, 6 Ctr Dr, Bethesda, MD 20892 USA.; Ray, K (reprint author), CSIR Cent Rd Res Inst, Acad Sci & Innovat Res, CRRI PO Delhi,Mathura Rd, New Delhi 110025, India. EM suddhasil.mookherjee@nih.gov; kunalray@acsir.res.in FU Council of Scientific and Industrial Research, Govt. of India [SIP-007, MLP-0016, NWP 004] FX The authors are grateful to the donors who participated in this study and to Dr. Keya Sen for helping with clinical evaluation of patients. We thank Ananya Ray-Soni for critically proofreading the article for improving the language and grammar of the article. The Council of Scientific and Industrial Research, Govt. of India supported the study through funding grants (SIP-007, MLP-0016, and NWP 004) and predoctoral fellowships to S.M., D.B., and S.C. NR 33 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1945-0265 EI 1945-0257 J9 GENET TEST MOL BIOMA JI Genet. Test. Mol. Biomark. PD OCT PY 2016 VL 20 IS 10 BP 633 EP 636 DI 10.1089/gtmb.2015.0344 PG 4 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA EA3AV UT WOS:000386470900012 PM 27533638 ER PT J AU Qian, F Feng, Y Zheng, YL Ogundiran, TO Ojengbede, O Zheng, W Blot, W Ambrosone, CB John, EM Bernstein, L Hu, JJ Ziegler, RG Nyante, S Bandera, EV Ingles, SA Press, MF Nathanson, KL Hennis, A Nemesure, B Ambs, S Kolonel, LN Olopade, OI Haiman, CA Huo, DZ AF Qian, Frank Feng, Ye Zheng, Yonglan Ogundiran, Temidayo O. Ojengbede, Oladosu Zheng, Wei Blot, William Ambrosone, Christine B. John, Esther M. Bernstein, Leslie Hu, Jennifer J. Ziegler, Regina G. Nyante, Sarah Bandera, Elisa V. Ingles, Sue A. Press, Michael F. Nathanson, Katherine L. Hennis, Anselm Nemesure, Barbara Ambs, Stefan Kolonel, Laurence N. Olopade, Olufunmilayo I. Haiman, Christopher A. Huo, Dezheng TI Genetic variants in microRNA and microRNA biogenesis pathway genes and breast cancer risk among women of African ancestry SO HUMAN GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; ESTROGEN-RECEPTOR; SUSCEPTIBILITY LOCI; INDIGENOUS AFRICANS; AMERICAN WOMEN; HUMAN-DISEASE; POPULATION; POLYMORPHISMS; EXPRESSION; BRCA1 AB MicroRNAs (miRNA) regulate breast biology by binding to specific RNA sequences, leading to RNA degradation and inhibition of translation of their target genes. While germline genetic variations may disrupt some of these interactions between miRNAs and their targets, studies assessing the relationship between genetic variations in the miRNA network and breast cancer risk are still limited, particularly among women of African ancestry. We systematically put together a list of 822 and 10,468 genetic variants among primary miRNA sequences and 38 genes in the miRNA biogenesis pathway, respectively; and examined their association with breast cancer risk in the ROOT consortium which includes women of African ancestry. Findings were replicated in an independent consortium. Logistic regression was used to estimate the odds ratio (OR) and 95 % confidence intervals (CI). For overall breast cancer risk, three single-nucleotide polymorphisms (SNPs) in miRNA biogenesis genes DROSHA rs78393591 (OR = 0.69, 95 % CI: 0.55-0.88, P = 0.003), ESR1 rs523736 (OR = 0.88, 95 % CI: 0.82-0.95, P = 3.99 x 10(-4)), and ZCCHC11 rs114101502 (OR = 1.33, 95 % CI: 1.11-1.59, P = 0.002), and one SNP in primary miRNA sequence (rs116159732 in miR-6826, OR = 0.74, 95 % CI: 0.63-0.89, P = 0.001) were found to have significant associations in both discovery and validation phases. In a subgroup analysis, two SNPs were associated with risk of estrogen receptor (ER)-negative breast cancer, and three SNPs were associated with risk of ER-positive breast cancer. Several variants in miRNA and miRNA biogenesis pathway genes were associated with breast cancer risk. Risk associations varied by ER status, suggesting potential new mechanisms in etiology. C1 [Qian, Frank; Zheng, Yonglan; Olopade, Olufunmilayo I.] Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA. [Feng, Ye; Ingles, Sue A.; Haiman, Christopher A.] Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. [Feng, Ye; Ingles, Sue A.; Press, Michael F.; Haiman, Christopher A.] Univ Southern Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA. [Ogundiran, Temidayo O.] Univ Ibadan, Dept Surg, Coll Med, Ibadan, Nigeria. [Ojengbede, Oladosu] Univ Ibadan, Coll Med, Ctr Populat & Reprod Hlth, Ibadan, Nigeria. [Zheng, Wei; Blot, William] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr, Div Epidemiol,Dept Med, Nashville, TN USA. [Ambrosone, Christine B.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA. [John, Esther M.] Stanford Univ, Sch Med Stanford, Dept Hlth Res & Policy Epidemiol, Stanford, CA 94305 USA. [John, Esther M.] Stanford Univ, Sch Med Stanford, Stanford Canc Inst, Stanford, CA 94305 USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA USA. [Hu, Jennifer J.] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. [Hu, Jennifer J.] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA. [Ziegler, Regina G.] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, DC USA. [Nyante, Sarah] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. [Nyante, Sarah] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. [Bandera, Elisa V.] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA. [Press, Michael F.] Univ Southern Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA USA. [Nathanson, Katherine L.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Hennis, Anselm] Univ West Indies, Chron Dis Res Ctr, Bridgetown, Barbados. [Hennis, Anselm] Univ West Indies, Res Inst Trop Med, Bridgetown, Barbados. [Nemesure, Barbara] SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY 11794 USA. [Ambs, Stefan] NCI, Human Carcinogenesis Lab, Bldg 37, Bethesda, MD 20892 USA. [Kolonel, Laurence N.] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA. [Huo, Dezheng] Univ Chicago, Dept Publ Hlth Sci, 5841 S Maryland Ave,MC 2007, Chicago, IL 60637 USA. RP Huo, DZ (reprint author), Univ Chicago, Dept Publ Hlth Sci, 5841 S Maryland Ave,MC 2007, Chicago, IL 60637 USA. EM dhuo@health.bsd.uchicago.edu FU National Cancer Institute [R01-CA142996, P50-CA125183, R01-CA89085] FX This work was supported by National Cancer Institute Grants R01-CA142996, P50-CA125183, and R01-CA89085. NR 75 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 EI 1432-1203 J9 HUM GENET JI Hum. Genet. PD OCT PY 2016 VL 135 IS 10 BP 1145 EP 1159 DI 10.1007/s00439-016-1707-1 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA DX2UC UT WOS:000384225700004 PM 27380242 ER PT J AU Santoro, N Eisenberg, E Trussell, JC Craig, LB Gracia, C Huang, H Alvero, R Casson, P Christman, G Coutifaris, C Diamond, M Jin, SS Legro, RS Robinson, RD Schlaff, WD Zhang, HP AF Santoro, Nanette Eisenberg, Esther Trussell, J. C. Craig, LaTasha B. Gracia, Clarisa Huang, Hao Alvero, Ruben Casson, Peter Christman, Gregory Coutifaris, Christos Diamond, Michael Jin, Susan Legro, Richard S. Robinson, Randal D. Schlaff, William D. Zhang, Heping CA Reprod Med Network Investigators TI Fertility-related quality of life from two RCT cohorts with infertility: unexplained infertility and polycystic ovary syndrome SO HUMAN REPRODUCTION LA English DT Article DE quality of life; polycystic ovary syndrome; unexplained infertility; FertiQOL; infertility ID IN-VITRO FERTILIZATION; MULTIPLE INTRAUTERINE GESTATIONS; STIMULATION AMIGOS TRIAL; PSYCHOLOGICAL DISTRESS; EMOTIONAL DISTRESS; PSYCHOMETRIC PROPERTIES; PROBLEM STRESS; SOCIAL IMPACT; WOMEN; COUPLES AB Does fertility-related quality of life (FertiQOL) differ by infertility diagnosis between women with polycystic ovary syndrome (PCOS) and their partners, compared with couples with unexplained infertility (UI)? Women with PCOS report lower QOL than those with UI, whereas males with UI report lower QOL than males with PCOS partners. The fertility-specific QOL survey, FertiQOL, has been used to examine fertility-related QOL in a number of worldwide cohorts. Few data have addressed fertility-related QOL as a function of infertility diagnosis. Overall, men report better QOL than women with infertility, and there is variation in FertiQOL scores across different samples from different countries. This was a prospective, cohort study derived from two concurrent, randomized clinical trials, and designed to examine QOL in infertile females with PCOS and UI at the time of enrollment compared with each other and their male partners; to compare concordance FertiQOL scores in this study across other worldwide cohorts; and to determine if baseline FertiQOL was associated with pregnancy outcome. Women with PCOS and their partners (n = 733 and n = 641, respectively), and couples with UI (n = 865 women and 849 men) completed a validated fertility-specific QOL survey (FertiQOL) at the time of the study screening visit. PCOS women were randomized to either clomiphene citrate or letrozole treatment; couples with UI were randomized to clomiphene citrate, letrozole or gonadotrophin plus IUI. FertiQOL results were compiled by diagnosis (PCOS or UI) and compared by diagnosis and sex using Wilcoxon Rank-Sum testing. Relationships between baseline FertiQOL and pregnancy outcomes were examined using logistic regression. Multivariable models were performed to assess the association between FertiQOL scores and key participant characteristics. Women with PCOS had lower total FertiQOL scores (72.3 +/- 14.8) than those with UI (77.1 +/- 12.8; P < 0.001); this was true for each domain (except Relational). These differences were largely explained by variation in BMI, hirsutism, household income and age. Women had lower overall FertiQOL scores than their male partners. Males with PCOS partners had higher scores than males with UI (84.9 +/- 10.2 versus 83.3 +/- 10.8; P = 0.003). Scores were not consistently associated with conception or pregnancy outcome. The use of multiple tests of association may have resulted in spurious statistically significant findings. Inherent sociodemographic differences between women with PCOS and those with UI largely account for the lower QOL in women with PCOS. Our study was unable to assess if changes in QOL affected pregnancy outcome as FertiQOL data were collected prior to treatment. Finally, the participants for both studies represent their local communities, but are not a population-based sample and thus firm conclusions about how representative these couples are to the general population must be made with caution. Women with PCOS with elevated BMI and hirsutism scores and with lower socioeconomic status may require more, targeted psychosocial support than those with other diagnoses. Possible attribution of infertility to the male partner appears to result in a lower QOL. There appears to be substantial national variation in FertiQOL scores, with US-based cohorts reporting overall higher QOL. This work was supported by National Institutes of Health (NIH)/Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Grants U10 HD39005 (to M.D.), U10 HD38992 (to R.S.L.), (to C.C.), U10 HD38998 (to R.A.), U10 HD055942 (to R.D.R.), HD055944 (to P.C.), U10 HD055936 (to G.C.), U10HD055925 (to H.Z.); and U10 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). Most importantly, this research was made possible by the funding by American Recovery and Reinvestment Act. N.S., E.E., J.C.T., C.G., H.H., R.A., P.C., G.C., C.C., M.D., S.J., W.D.S. and H.Z. report no conflicts of interests/disclosures. L.B.C. reports research support from Ferring Pharmaceuticals and Roche Diagnostics; R.S.L. reports receipt of consulting fees from AstraZeneca, Euroscreen, Sprout Pharmaceuticals, Taken, Kindex, Clarus and Bayer, Inc., and research support from AstraZeneca and Ferring Pharmaceuticals. R.D.R. reports research support from AbbVie. Pregnancy in Polycystic Ovary Syndrome II (PPCOS II), NCT00719186; Assessment of Multiple Intrauterine Gestations in Ovulation Stimulation (AMIGOS) NCT01044862, clinicaltrials.gov. PPCOS II 17 July 2008; AMIGOS 7 January 2010. PPCOS II 19 February 2009; AMIGOS 2 August 2010. C1 [Santoro, Nanette; Alvero, Ruben] Univ Colorado, Dept Obstet & Gynecol, Sch Med, 12631 E 17th Ave AO,Room 4010, Aurora, CO 80045 USA. [Eisenberg, Esther] NICHD, Fertil & Infertil Branch, NIH, Bethesda, MD 20892 USA. [Trussell, J. C.] SUNY Upstate Med Univ, Dept Urol, 750 E Adams St, Syracuse, NY 13210 USA. [Craig, LaTasha B.] Univ Oklahoma, Hlth Sci Ctr, Dept Obstet & Gynecol, POB 26901,WP 2410, Oklahoma City, OK 73126 USA. [Gracia, Clarisa; Coutifaris, Christos] Univ Penn, Dept Obstet & Gynecol, Penn Fertil Ctr, 3701 Market St, Philadelphia, PA 19104 USA. [Huang, Hao; Jin, Susan; Zhang, Heping] Yale Sch Publ Hlth, Collaborat Ctr Stat Sci, 60 Coll St, New Haven, CT 06520 USA. [Legro, Richard S.] Penn State Coll Med, 500 Univ Dr, Hershey, PA 17033 USA. [Robinson, Randal D.] Univ Texas San Antonio, Hlth Sci Ctr, 8300 Floyd Curl Dr, San Antonio, TX 78229 USA. [Casson, Peter] Northeastern Reprod Med, 105 West View Rd Suite 305, Colchester, VT 05446 USA. [Christman, Gregory] Univ Florida, Coll Med, Dept Obstet & Gynecol, 1600 SW Archer Rd, Gainesville, FL 32611 USA. [Diamond, Michael] Georgia Regents Univ, Med Coll Georgia, 1120 15th St,BA-7300, Augusta, GA 30912 USA. [Schlaff, William D.] Thomas Jefferson Univ, Dept Obstet & Gynecol, 834 Chestnut St,Suite 400, Philadelphia, PA 19107 USA. [Alvero, Ruben] Brown Univ, Warren Alpert Med Sch, Dept Obstet & Gynecol, Providence, RI 02903 USA. RP Santoro, N (reprint author), Univ Colorado, Dept Obstet & Gynecol, Sch Med, 12631 E 17th Ave AO,Room 4010, Aurora, CO 80045 USA. EM nanette.santoro@ucdenver.edu FU National Institutes of Health (NIH)/Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [U10 HD39005, U10 HD38992, U10 HD38998, U10 HD055942, HD055944, U10 HD055936, U10HD055925, U10 U54-HD29834]; American Recovery and Reinvestment Act FX This work was supported by National Institutes of Health (NIH)/Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Grants U10 HD39005 (to M.D.), U10 HD38992 (to R.S.L., to C.C.), U10 HD38998 (to R.A.), U10 HD055942 (to R.D.R.), HD055944 (to P.C.), U10 HD055936 (to G.C.), U10HD055925 (to H.Z.); and U10 U54-HD29834 (to the University of Virginia Center for Research in Reproduction Ligand Assay and AnalysisCore of the Specialized Cooperative Centers Program in Reproduction and Infertility Research). Most importantly, this research was made possible by the funding by American Recovery and Reinvestment Act. NR 62 TC 0 Z9 0 U1 9 U2 9 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 OCT PY 2016 VL 31 IS 10 BP 2268 EP 2279 DI 10.1093/humrep/dew175 PG 12 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DZ7ZH UT WOS:000386087000014 PM 27402910 ER PT J AU Eisenberg, ML Sundaram, R Maisog, J Louis, GMB AF Eisenberg, Michael L. Sundaram, Rajeshwari Maisog, Jose Louis, Germaine M. Buck TI Diabetes, medical comorbidities and couple fecundity SO HUMAN REPRODUCTION LA English DT Article DE diabetes; hypertension; hyperlipidemia; hyperthyroidism; hypothyroidism; fertility ID SEMEN QUALITY DATA; TIME-TO-PREGNANCY; BODY-MASS INDEX; MALE-INFERTILITY; UNITED-STATES; LIPID CONCENTRATIONS; METABOLIC SYNDROME; LIFE; MELLITUS; INSULIN AB What is the relationship between couple's health and fecundity in a preconception cohort? Somatic health may impact fecundity in men and women as couples whose male partner had diabetes or whose female partner had two or more medical conditions had a longer time-to-pregnancy (TTP). The impact of somatic health on human fecundity is hypothesized given the reported declines in spermatogenesis and ovulation among individuals with certain medical comorbidities. A population-based prospective cohort study recruiting couples from 16 counties in Michigan and Texas (2005-2009) using sampling frameworks allowing for identification of couples planning pregnancy in the near future. Five hundred and one couples desiring pregnancy and discontinuing contraception were followed-up for 12 months or until a human chorionic gonadotropin pregnancy was detected. In all, 33 (21.4%) female and 41 (26.6%) male partners had medical conditions at baseline. Couples' medical comorbidity was associated with pregnancy status. Diabetes in either partner was associated with diminished fecundity, as measured by a longer TTP. Specifically, fecundability odds ratios (FORs) were below 1, indicating a longer TTP, for male partners with diabetes (0.35, 95% confidence interval (CI): 0.14-0.86) even in adjusted models (0.35, 95% CI: 0.13-0.88). Female partners with diabetes had comparable reductions in FORs; however, the analyses did not reach statistical significance (0.26, 95% CI: 0.03-1.98). Female partners with two or more medical conditions had a significantly longer TTP compared with women with no health problems (0.36, 95% CI: 0.14-0.92). Importantly, the presence of medical conditions was not associated with sexual frequency. We cannot rule out residual confounding, Type 2 errors for less prevalent medical conditions, or chance findings in light of the multiple comparisons made in the analysis. The findings require cautious interpretation given that medical diagnoses are subject to possible reporting errors, although we are unaware of any potential biases that may have been introduced, as participants were unaware of how long it would take to become pregnant upon enrollment. The current report suggests a relationship between male and female diabetes and fecundity, and possibly somatic health more globally. Moreover, while the mechanism is uncertain, if corroborated, our data suggest that early evaluation and treatment may be warranted for diabetics prior to attempting to conceive. Intramural research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Contract nos. #N01-HD-3-3355, N01-HD-3-3356 and N01-HD-3-3358). The authors have no conflicts of interest to declare. C1 [Eisenberg, Michael L.] Stanford Univ, Dept Urol, 300 Pasteur Dr, Stanford, CA 94305 USA. [Eisenberg, Michael L.] Stanford Univ, Dept Obstet & Gynecol, 300 Pasteur Dr, Stanford, CA 94305 USA. [Sundaram, Rajeshwari] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA. [Maisog, Jose] Glotech Inc, 1801 Res Blvd,Suite 605, Rockville, MD 20852 USA. [Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA. RP Eisenberg, ML (reprint author), Stanford Univ, Sch Med, Dept Urol, Male Reprod Med & Surg, 300 Pasteur Dr, Stanford, CA 94305 USA. EM eisenberg@stanford.edu OI Sundaram, Rajeshwari/0000-0002-6918-5002; Buck Louis, Germaine/0000-0002-1774-4490 FU Intramural research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development [N01-HD-3-3355, N01-HD-3-3356, N01-HD-3-3358] FX Intramural research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Contract nos. # N01-HD-3-3355, N01-HD-3-3356 and N01-HD-3-3358). NR 41 TC 0 Z9 0 U1 2 U2 2 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 OCT PY 2016 VL 31 IS 10 BP 2369 EP 2376 DI 10.1093/humrep/dew200 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA DZ7ZH UT WOS:000386087000025 PM 27591240 ER PT J AU Fleg, JL Evans, GW Margolis, KL Barzilay, J Basile, JN Bigger, JT Cutler, JA Grimm, R Pedley, C Peterson, K Pop-Busui, R Sperl-Hillen, J Cushman, WC AF Fleg, Jerome L. Evans, Gregory W. Margolis, Karen L. Barzilay, Joshua Basile, Jan N. Bigger, J. Thomas Cutler, Jeffrey A. Grimm, Richard Pedley, Carolyn Peterson, Kevin Pop-Busui, Rodica Sperl-Hillen, JoAnn Cushman, William C. TI Orthostatic Hypotension in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) Blood Pressure Trial: Prevalence, Incidence, and Prognostic Significance SO HYPERTENSION LA English DT Article DE cardiovascular diseases; clinical trials; randomized; diabetes mellitus; type 2; hypertension; hypotension; orthostatic ID POSTURAL HYPOTENSION; ATHEROSCLEROSIS RISK; HEART-FAILURE; PROGRAM; INSULIN; VASODILATION; HYPERTENSION; COMMUNITIES; MORTALITY AB Orthostatic hypotension (OH) is associated with hypertension and diabetes mellitus. However, in populations with both hypertension and diabetes mellitus, its prevalence, the effect of intensive versus standard systolic blood pressure (BP) targets on incident OH, and its prognostic significance are unclear. In 4266 participants in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) BP trial, seated BP was measured 3x, followed by readings every minute for 3 minutes after standing. Orthostatic BP change, calculated as the minimum standing minus the mean seated systolic BP and diastolic BP, was assessed at baseline, 12 months, and 48 months. The relationship between OH and clinical outcomes (total and cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, heart failure hospitalization or death and the primary composite outcome of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) was assessed using proportional hazards analysis. Consensus OH, defined by orthostatic decline in systolic BP 20 mmHg or diastolic BP 10 mmHg, occurred at 1 time point in 20% of participants. Neither age nor systolic BP treatment target (intensive, <120 mmHg versus standard, <140 mmHg) was related to OH incidence. Over a median follow-up of 46.9 months, OH was associated with increased risk of total death (hazard ratio, 1.61; 95% confidence interval, 1.11-2.36) and heart failure death/hospitalization (hazard ratio, 1.85, 95% confidence interval, 1.17-2.93), but not with the primary outcome or other prespecified outcomes. In patients with type 2 diabetes mellitus and hypertension, OH was common, not associated with intensive versus standard BP treatment goals, and predicted increased mortality and heart failure events. C1 [Fleg, Jerome L.; Cutler, Jeffrey A.] NHLBI, Bldg 10, Bethesda, MD 20892 USA. [Evans, Gregory W.; Pedley, Carolyn] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Margolis, Karen L.; Sperl-Hillen, JoAnn] Hlth Partners Inst Educ & Res, Minneapolis, MN USA. [Barzilay, Joshua] Kaiser Permanente Georgia, Atlanta, GA USA. [Basile, Jan N.] Med Univ South Carolina, Charleston, SC USA. [Bigger, J. Thomas] Columbia Univ, Sch Med, New York, NY USA. [Grimm, Richard] Berman Ctr Outcomes & Clin Res, Minneapolis, MN USA. [Peterson, Kevin] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Pop-Busui, Rodica] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Cushman, William C.] Vet Affairs Med Ctr, Memphis, TN USA. RP Fleg, JL (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Room 8154, Bethesda, MD 20892 USA. EM flegj@nhlbi.nih.gov FU National Heart, Lung, and Blood Institute FX The ACCORD (Action to Control Cardiovascular Risk in Diabetes) Blood Pressure trial was funded by a contract from the National Heart, Lung, and Blood Institute. NR 24 TC 3 Z9 3 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD OCT PY 2016 VL 68 IS 4 BP 888 EP 895 DI 10.1161/HYPERTENSIONAHA.116.07474 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DX1LB UT WOS:000384127800015 PM 27504006 ER PT J AU Sung, VW Borello-France, D Dunivan, G Gantz, M Lukacz, ES Moalli, P Newman, DK Richter, HE Ridgeway, B Smith, AL Weidner, AC Meikle, S AF Sung, Vivian W. Borello-France, Diane Dunivan, Gena Gantz, Marie Lukacz, Emily S. Moalli, Pamela Newman, Diane K. Richter, Holly E. Ridgeway, Beri Smith, Ariana L. Weidner, Alison C. Meikle, Susan CA Pelvic Floor Disorders Network TI Methods for a multicenter randomized trial for mixed urinary incontinence: rationale and patient-centeredness of the ESTEEM trial SO INTERNATIONAL UROGYNECOLOGY JOURNAL LA English DT Article DE Female; Mixed urinary incontinence; Clinical trials; Sling; Behavioral therapy ID QUALITY-OF-LIFE; PELVIC FLOOR DISORDERS; STRESS-INCONTINENCE; BEHAVIORAL-THERAPY; US WOMEN; OVERACTIVE BLADDER; URGE INCONTINENCE; TRACT SYMPTOMS; ORGAN PROLAPSE; PREVALENCE AB Introduction and hypothesis Mixed urinary incontinence (MUI) can be a challenging condition to manage. We describe the protocol design and rationale for the Effects of Surgical Treatment Enhanced with Exercise for Mixed Urinary Incontinence (ESTEEM) trial, designed to compare a combined conservative and surgical treatment approach versus surgery alone for improving patient-centered MUI outcomes at 12 months. Methods ESTEEM is a multisite, prospective, randomized trial of female participants with MUI randomized to a standardized perioperative behavioral/pelvic floor exercise intervention phis midurethral sling versus midurethral sling alone. We describe our methods and four challenges encountered during the design phase: defusing the study population, selecting relevant patient-centered outcomes, determining sample size estimates using a patient-reported outcome measure, and designing an analysis plan that accommodates MUI failure rates. A central theme in the design was patient centeredness, which guided many key decisions. Our primary outcome is patient reported MUI symptoms measured using the Urogenital Distress Inventory (UDI) score at 12 months. Secondary outcomes include quality of life, sexual function, cost-effectiveness, time to failure, and need for additional treatment. Results The final study design was implemented in November 2013 across eight clinical sites in the Pelvic Floor Disorders Network. As of 27 February 2016, 433 total/472 targeted participants had been randomized. Conclusions We describe the ESTEEM protocol and our methods for reaching consensus for methodological challenges in designing a trial for MUI by maintaining the patient perspective at the core of key decisions. This trial will provide information that can directly impact patient care and clinical decision making. C1 [Sung, Vivian W.] Brown Univ, Dept Obstet & Gynecol, Alpert Med Sch, Div Urogynecol & Reconstruct Pelv Surg, 101 Plain St 5th Floor, Providence, RI 02903 USA. [Sung, Vivian W.] Brown Univ, Warren Alpert Med Sch, Women & Infants Hosp Rhode Isl, Div Urogynecol & Reconstruct Pelv Surg, 101 Plain St 5th Floor, Providence, RI 02903 USA. [Borello-France, Diane] Duquesne Univ, Dept Phys Therapy, Rangos Sch Hlth Sci, Pittsburgh, PA 15219 USA. [Dunivan, Gena] Univ New Mexico, Dept Obstet & Gynecol, Div Urogynecol, Albuquerque, NM 87131 USA. [Gantz, Marie] RTI Int, Social Stat & Environm Sci, Res Triangle Pk, NC USA. [Lukacz, Emily S.] UC San Diego Hlth Syst, Dept Reprod Med, Div Female Pelv Med & Reconstruct Surg, San Diego, CA USA. [Moalli, Pamela] Univ Pittsburgh, Med Ctr, Dept Obstet Gynecol & Reprod Sci, Womens Ctr Bladder & Pelv Hlth,Div Urogynecol & R, Pittsburgh, PA USA. [Newman, Diane K.; Smith, Ariana L.] Univ Penn Hlth Syst, Dept Surg, Div Urol, Philadelphia, PA USA. [Richter, Holly E.] Univ Alabama Birmingham, Dept Obstet & Gynecol, Div Urogynecol & Pelv Reconstruct Surg, Birmingham, AL 35294 USA. [Ridgeway, Beri] Cleveland Clin, Ctr Urogynecol & Reconstruct Pelv Surg, Obstet Gynecol & Womens Hlth Inst, Cleveland, OH 44106 USA. [Weidner, Alison C.] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Div Urogynecol, Durham, NC 27710 USA. [Meikle, Susan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Sung, VW (reprint author), Brown Univ, Dept Obstet & Gynecol, Alpert Med Sch, Div Urogynecol & Reconstruct Pelv Surg, 101 Plain St 5th Floor, Providence, RI 02903 USA.; Sung, VW (reprint author), Brown Univ, Warren Alpert Med Sch, Women & Infants Hosp Rhode Isl, Div Urogynecol & Reconstruct Pelv Surg, 101 Plain St 5th Floor, Providence, RI 02903 USA. EM vsung@wihri.org OI Markland, Alayne/0000-0002-6567-6744 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [U10 HD041261, U10 HD069013, U10 HD054214, U10 HD054215, U10 HD041267, U10 HD069025, U10 HD069010, U10 HD069006, U01 HD069031]; National Institutes of Health Office of Research on Women's Health FX Supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (U10 HD041261, U10 HD069013, U10 HD054214, U10 HD054215, U10 HD041267, U10 HD069025, U10 HD069010, U10 HD069006, U01 HD069031) and the National Institutes of Health Office of Research on Women's Health. NR 60 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-3462 EI 1433-3023 J9 INT UROGYNECOL J JI Int. Urogynecol. J. PD OCT PY 2016 VL 27 IS 10 BP 1479 EP 1490 DI 10.1007/s00192-016-3031-7 PG 12 WC Obstetrics & Gynecology; Urology & Nephrology SC Obstetrics & Gynecology; Urology & Nephrology GA EA1LR UT WOS:000386354200004 PM 27287818 ER PT J AU Meyer, BJ Byrne, M Parletta, N Gow, R Hibbeln, JR AF Meyer, Barbara J. Byrne, Mitchell Parletta, Natalie Gow, Rachel Hibbeln, Joseph R. TI Fish Oil and Impulsive Aggressive Behavior SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Letter ID YOUNG-ADULT PRISONERS; DISORDER; CHILDREN; TRIAL C1 [Meyer, Barbara J.] Univ Wollongong, Sch Med, Northfields Ave, Wollongong, NSW 2522, Australia. [Byrne, Mitchell] Univ Wollongong, Sch Psychol, Wollongong, NSW 2522, Australia. [Parletta, Natalie] Univ S Australia, Sansom Inst Hlth Res, Sch Populat Hlth, Adelaide, SA, Australia. [Gow, Rachel; Hibbeln, Joseph R.] NIAAA, Sect Nutr Neurosci, Lab Membrane Biol & Biophys, NIH, Bethesda, MD USA. RP Meyer, BJ (reprint author), Univ Wollongong, Sch Med, Northfields Ave, Wollongong, NSW 2522, Australia. EM bmeyer@uow.edu.au OI Byrne, Mitchell/0000-0003-0823-2917 NR 5 TC 0 Z9 0 U1 4 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 EI 1557-8992 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD OCT PY 2016 VL 26 IS 8 BP 766 EP 766 DI 10.1089/cap.2015.0065 PG 1 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA DZ8QN UT WOS:000386136000017 PM 26217883 ER PT J AU da Cunha, MG Franchin, M de Paula-Eduardo, LF Freires, IA Beutler, JA de Alencar, SM Ikegaki, M Tabchoury, CPM Cunha, TM Rosalen, PL AF da Cunha, Marcos Guilherme Franchin, Marcelo de Paula-Eduardo, Laila Facin Freires, Irlan Almeida Beutler, John A. de Alencar, Severino Matias Ikegaki, Masaharu Machado Tabchoury, Cinthia Pereira Cunha, Thiago Mattar Rosalen, Pedro Luiz TI Anti-inflammatory and anti-biofilm properties of ent-nemorosone from Brazilian geopropolis SO JOURNAL OF FUNCTIONAL FOODS LA English DT Article DE Geopropolis; ent-Nemorosone; Anti-inflammatory; Anti-biofilm ID NF-KAPPA-B; MECHANICAL INFLAMMATORY HYPERNOCICEPTION; ACTIVATED PROTEIN-KINASES; STREPTOCOCCUS-MUTANS; RED PROPOLIS; MELIPONA-SCUTELLARIS; TNF-ALPHA; 7-EPICLUSIANONE; BENZOPHENONE; RECRUITMENT AB ent-Nemorosone is a benzophenone isolated from geopropolis from Melipona scutellaris whose biological properties remain unexplored. Herein, we evaluated the anti-inflammatory activity of ent-nemorosone by in vivo neutrophil migration and TNF-alpha quantification, as well as by in vitro TNF-alpha quantification, ERK 1/2 phosphorylation, NF-kB activation and nuclear translocation of p65 in stimulated macrophages. ent-Nemorosone was also tested for its antimicrobial effects against Streptococcus mutans biofilm adhesion, polysaccharide production, and viability ent-Nemorosone reduced the influx of neutrophils and TNF-alpha release into the peritoneal cavity of mice, as well as the in vitro TNF-alpha levels, ERK 1/2 phosphorylation, NF-kB activation and nuclear p65 translocation. Furthermore, this compound inhibited biofilm adhesion and reduced the amount of extra- and intracellular polysaccharides synthesized by S. mutans. Thus, ent-nemorosone showed promising anti-inflammatory activity by acting on TNF-alpha release in macrophages, as well as anti-biofilm properties by reducing S. mutans polysaccharide production. (C) 2016 Elsevier Ltd. All rights reserved. C1 [da Cunha, Marcos Guilherme; Franchin, Marcelo; de Paula-Eduardo, Laila Facin; Freires, Irlan Almeida; Machado Tabchoury, Cinthia Pereira; Rosalen, Pedro Luiz] Univ Estadual Campinas, UNICAMP, Piracicaba Dent Sch, Dept Physiol Sci, Campinas, SP, Brazil. [da Cunha, Marcos Guilherme; Beutler, John A.] NCI, Mol Targets Lab, NIH, Frederick, MD 21701 USA. [de Alencar, Severino Matias] Univ Sao Paulo, Luiz de Queiroz Coll Agr, Dept Agrifood Ind Food & Nutr, Piracicaba, SP, Brazil. [Ikegaki, Masaharu] Univ Fed Alfenas, Coll Pharmaceut Sci, Alfenas, MG, Brazil. [Cunha, Thiago Mattar] Univ Sao Paulo, Ribeirao Preto Med Sch, Ribeirao Preto, SP, Brazil. RP Rosalen, PL (reprint author), Univ Estadual Campinas, UNICAMP, Piracicaba Dent Sch, Dept Physiol Sci, Campinas, SP, Brazil. EM rosalen@fop.unicamp.br RI Alencar, Severino/B-7743-2012; CEPID, CRID/J-2644-2015; Cunha, Thiago/B-7729-2012; OI Alencar, Severino/0000-0002-6637-7973; Cunha, Thiago/0000-0003-1084-0065; Freires, Irlan/0000-0002-1079-6941 FU FAPESP [2011/16501-3, 2011/23635-6, 2012/22378-2, 2012/22002-2]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research [1ZIABC011469-04] FX This research was supported by FAPESP (No. 2011/16501-3, 2011/23635-6, 2012/22378-2 and 2012/22002-2) and by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (No. 1ZIABC011469-04). The authors would like to thank Mr. Jose Emidio Borges de Souza for providing the geopropolis samples. We thank Sergey Tarasov and Marzena Dyba (Biophysics Resource Core, Structural Biophysics Laboratory, CCR) for assistance with mass spectrometry. NR 33 TC 0 Z9 0 U1 7 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1756-4646 J9 J FUNCT FOODS JI J. Funct. Food. PD OCT PY 2016 VL 26 BP 27 EP 35 DI 10.1016/j.jff.2016.07.009 PG 9 WC Food Science & Technology SC Food Science & Technology GA DZ9KG UT WOS:000386193400003 ER PT J AU Mudd, JC Brenchley, JM AF Mudd, Joseph C. Brenchley, Jason M. TI Gut Mucosal Barrier Dysfunction, Microbial Dysbiosis, and Their Role in HIV-1 Disease Progression SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE HIV-1 pathognesis; gastrointestinal tract; microbiome; Th17; cART; residual inflammation; probiotics ID HUMAN-IMMUNODEFICIENCY-VIRUS; SYSTEMIC IMMUNE ACTIVATION; T-CELL-ACTIVATION; INFLAMMATORY-BOWEL-DISEASE; INFECTED RHESUS MACAQUES; INNATE LYMPHOID-CELLS; ANTIRETROVIRAL THERAPY; SIV INFECTION; INTESTINAL INFLAMMATION; VIRAL SUPPRESSION AB Distinct pathological events occur within the gastrointestinal (GI) tract of Asian macaques with progressive simian immunodeficiency virus (SIV) infection and humans with human immunodeficiency virus type 1 (HIV-1) infection that are critical in shaping disease course. These events include depletion and functional alteration of GI-resident CD4(+) T cells, loss of antigen-presenting cells, loss of innate lymphocytes, and possible alterations to the composition of the gut microbiota. These contribute to structural damage to the GI tract and systemic translocation of GI tract microbial products. These translocated microbial products directly stimulate the immune system, and there is now overwhelming evidence that this drives chronic immune activation in HIV-1 and SIV infection. While combined antiretroviral therapy (cART) in HIV-1-infected subjects generally allows for immune reconstitution in peripheral blood, reconstitution of the GI tract occurs at a much slower pace, and both immunological and structural abnormalities persist in the GI tract. Importantly, studies of large cohorts of individuals have linked suboptimal GI reconstitution to residual inflammation and heightened morbidities in HIV-1-infected cART recipients. As a result, current era treatments aimed at augmenting restoration of the GI tract hold promise in returning cART recipients to full health. C1 [Mudd, Joseph C.; Brenchley, Jason M.] NIAID, Parasit Dis Lab, NIH, 4 Mem Dr, Bethesda, MD 20814 USA. RP Brenchley, JM (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Mem Dr, Bethesda, MD 20814 USA. EM jbrenchl@niaid.nih.gov FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 98 TC 2 Z9 2 U1 6 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD OCT 1 PY 2016 VL 214 SU 2 BP S58 EP S66 DI 10.1093/infdis/jiw258 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DZ8UP UT WOS:000386147600004 PM 27625432 ER PT J AU Du Toit, J Millum, J AF Du Toit, Jessica Millum, Joseph TI Are Indirect Benefits Relevant to Health Care Allocation Decisions? SO JOURNAL OF MEDICINE AND PHILOSOPHY LA English DT Article DE direct benefits; indirect benefits; resource allocation ID INFLUENZA; HEADACHES; COUNT; LIVES AB When allocating scarce healthcare resources, the expected benefits of alternative allocations matter. But, there are different kinds of benefits. Some are direct benefits to the recipient of the resource such as the health improvements of receiving treatment. Others are indirect benefits to third parties such as the economic gains from having a healthier workforce. This article considers whether only the direct benefits of alternative healthcare resource allocations are relevant to allocation decisions, or whether indirect benefits are relevant too. First, we distinguish different conceptions of direct and indirect benefits and argue that only a recipient conception could be morally relevant. We analyze four arguments for thinking that indirect benefits should not count and argue that none is successful in showing that the indirectness of a benefit is a good reason not to count it. We conclude that direct and indirect benefits should be evaluated in the same way. C1 [Du Toit, Jessica; Millum, Joseph] NIH, Bldg 10, Bethesda, MD 20892 USA. RP Du Toit, J (reprint author), NIH, Dept Bioeth, 10 Ctr Dr,Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM jess.dutoit@gmail.com FU National Institutes of Health Clinical Center; Fogarty International Center FX The authors would like to thank audiences at the NIH Clinical Center Department of Bioethics and the New Scholars in Bioethics 4th Annual Symposium for helpful comments on earlier drafts of this article. This work was supported, in part, by intramural funds from the National Institutes of Health Clinical Center and Fogarty International Center. The views expressed are the authors' own. They do not represent the position or policy of the National Institutes of Health, US Public Health Service, or the Department of Health and Human Services. NR 29 TC 2 Z9 2 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0360-5310 EI 1744-5019 J9 J MED PHILOS JI J. Med. Philos. PD OCT PY 2016 VL 41 IS 5 BP 540 EP 557 DI 10.1093/jmp/jhw018 PG 18 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA DZ8WB UT WOS:000386152000007 PM 27465773 ER PT J AU Moaddel, R Fabbri, E Khadeer, MA Carlson, OD Gonzalez-Freire, M Zhang, PB Semba, RD Ferrucci, L AF Moaddel, Ruin Fabbri, Elisa Khadeer, Mohammed A. Carlson, Olga D. Gonzalez-Freire, Marta Zhang, Pingbo Semba, Richard D. Ferrucci, Luigi TI Plasma Biomarkers of Poor Muscle Quality in Older Men and Women from the Baltimore Longitudinal Study of Aging SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Sarcopenia; Muscles; Metabolomics ID SKELETAL-MUSCLE; INDOLEAMINE 2,3-DIOXYGENASE; BODY-COMPOSITION; HEALTHY-MEN; STRENGTH; MASS; MORTALITY; POLYAMINES; ADULTS; AGE AB Aging is characterized by progressive decline in muscle mass, strength, and quality all of which contribute to functional impairment, falls, mobility disability, and frailty. Circulating factors may provide clues on the mechanisms for decline in muscle quality with aging. Characterizing the metabolic profile associated with reduced muscle quality in older persons could have important translational implications for the early identification of subjects at high risk of developing sarcopenia and the identification of targets for new preventive strategies and treatments. In a pilot cross-sectional, case-control study nested in the Baltimore Longitudinal Study on Aging, we compared circulating metabolites between 79 participants with low muscle quality ratio and 79 controls with high muscle quality, matched by age, sex, and height. The concentrations of 180 metabolites were determined by LC MS/MS, using the Biocrates p180 system, a targeted metabolomics approach. Participants with low muscle quality had significantly higher levels of leucine, isoleucine, tryptophan, serotonin, and methionine, while those with high muscle quality had significantly lower levels of putrescine and the selected phophatidylcholine (PCs) and lysoPCs. The results of this study open a new road for future investigations aimed at identifying new metabolic pathways involved in the decline of muscle quality with aging. C1 [Moaddel, Ruin; Fabbri, Elisa; Khadeer, Mohammed A.; Carlson, Olga D.; Gonzalez-Freire, Marta; Ferrucci, Luigi] NIA, Intramural Res Programs, NIH, Baltimore, MD 21224 USA. [Zhang, Pingbo; Semba, Richard D.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. RP Moaddel, R (reprint author), 251 Bayview Blvd, Baltimore, MD 21224 USA. EM moaddelru@mail.nih.gov FU Intramural Research Program of the National Institutes of Health; National Institute on Aging FX Intramural Research Program of the National Institutes of Health; National Institute on Aging. NR 46 TC 1 Z9 1 U1 2 U2 2 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 OCT PY 2016 VL 71 IS 10 BP 1266 EP 1272 DI 10.1093/gerona/glw046 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA DZ7WI UT WOS:000386078800003 PM 27029859 ER PT J AU Shea, MK Loeser, RF Hsu, FC Booth, SL Nevitt, M Simonsick, EM Strotmeyer, ES Vermeer, C Kritchevsky, SB AF Shea, M. Kyla Loeser, Richard F. Hsu, Fang-Chi Booth, Sarah L. Nevitt, Michael Simonsick, Eleanor M. Strotmeyer, Elsa S. Vermeer, Cees Kritchevsky, Stephen B. CA Hlth ABC Study TI Vitamin K Status and Lower Extremity Function in 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 Physical performance; Nutrition; Physical function; Vitamin K ID MATRIX GLA PROTEIN; PHYSICAL PERFORMANCE; KNEE OSTEOARTHRITIS; MOBILITY DISABILITY; MEANINGFUL CHANGE; CLINICAL-TRIAL; ASSOCIATION; CALCIFICATION; WOMEN; INFLAMMATION AB While low vitamin K status has been associated with several chronic diseases that can lead to lower extremity disability, it is not known if low vitamin K status is associated with worse lower extremity function. Vitamin K status was measured according to plasma phylloquinone (vitamin K1) and dephosphorylated-uncarboxylated MGP (dp-ucMGP) in 1,089 community-dwelling older adults (mean +/- SD age =74 +/- 3 years; 67% female). Lower extremity function was assessed using the short physical performance battery (SPPB), gait speed, and isokinetic leg strength. Linear regression and mixed models were used to determine the cross-sectional and longitudinal associations between vitamin K status and functional outcome measures. Cross-sectionally, higher plasma phylloquinone was associated with better SPPB scores and 20-m gait speed (p a parts per thousand currency sign .05). After 4-5 years, those with a parts per thousand yen1.0nM plasma phylloquinone (the concentration achieved when recommended intakes are met) had better SPPB scores (p = .03) and 20-m gait speed (p < .05). Lower plasma dp-ucMGP (reflective of better vitamin K status) was associated with better SPPB scores and leg strength cross-sectionally (p a parts per thousand currency sign .04), but not longitudinally. Neither measure of vitamin K status was associated with walking endurance or with the rate of decline in function. Older adults with higher vitamin K status had better physical performance scores at baseline, but data are less consistent longitudinally. Since lower extremity disability is a common consequence of multiple chronic diseases for which a role of vitamin K has been suggested, future studies are needed to determine if vitamin K supplementation could improve function in those with vitamin K insufficiency and clarify underlying mechanism(s). C1 [Shea, M. Kyla; Booth, Sarah L.] Tufts Univ, USDA, Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA. [Loeser, Richard F.] Univ N Carolina, Div Rheumatol Allergy & Immunol, Chapel Hill, NC USA. [Hsu, Fang-Chi] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA. [Nevitt, Michael] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Simonsick, Eleanor M.] NIA, NIH, Baltimore, MD 21224 USA. [Strotmeyer, Elsa S.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Vermeer, Cees] Maastricht Univ, VitaK, NL-6200 MD Maastricht, Netherlands. [Kritchevsky, Stephen B.] Wake Forest Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. RP Shea, MK (reprint author), Tufts Univ, USDA, Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA. EM kyla.shea@tufts.edu FU NIH Intramural Research Program; NIA; NINR [R01-NR012459]; NIAMS [R21AR062284, K01AR063167]; Arthritis Foundation New Investigator Grant; USDA, Agricultural Research Service Cooperative Agreement [58-1950-7-707]; [N01-AG-6-2101]; [N01-AG-6-2103]; [N01-AG-6-2106]; [R01-AG028050] FX This study was supported by the NIH Intramural Research Program, the NIA and contracts (N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; R01-AG028050); the NINR (R01-NR012459); the NIAMS (R21AR062284, K01AR063167); an Arthritis Foundation New Investigator Grant and the USDA, Agricultural Research Service Cooperative Agreement (58-1950-7-707). NR 30 TC 1 Z9 1 U1 1 U2 1 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 OCT PY 2016 VL 71 IS 10 BP 1348 EP 1355 DI 10.1093/gerona/glv209 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA DZ7WI UT WOS:000386078800014 PM 26576842 ER PT J AU McNeil, SE AF McNeil, Scott E. TI Evaluation of nanomedicines: stick to the basics SO NATURE REVIEWS MATERIALS LA English DT Letter ID DELIVERY; TUMORS C1 [McNeil, Scott E.] NCI, Nanotechnol Characterizat Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. RP McNeil, SE (reprint author), NCI, Nanotechnol Characterizat Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. EM ncl@mail.nih.gov NR 9 TC 0 Z9 0 U1 7 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2058-8437 J9 NAT REV MATER JI Nat. Rev. Mater. PD OCT PY 2016 VL 1 IS 10 PG 2 WC Materials Science, Multidisciplinary SC Materials Science GA EA0ET UT WOS:000386259300005 ER PT J AU Liao, Y Berghoff, AS Osswald, M Ilhan-Mutlu, A Gil, B Thome, C Ratliff, M Steeg, P Wick, W Winkler, F AF Liao, Y. Berghoff, A. S. Osswald, M. Ilhan-Mutlu, A. Gil, B. Thome, C. Ratliff, M. Steeg, P. Wick, W. Winkler, F. TI IDENTIFICATION AND CHARACTERIZATION OF BRAIN METASTASIS INITIATING CELLS SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th Meeting of the European-Association-of-Neuro-Oncology CY OCT 12-16, 2016 CL GERMANY SP European Assoc Neuro Oncol C1 [Liao, Y.; Berghoff, A. S.; Osswald, M.; Thome, C.; Ratliff, M.; Wick, W.; Winkler, F.] German Canc Res Ctr, Clin Cooperat Unit Neurooncol, German Canc Consortium DKTK, Heidelberg, Germany. [Liao, Y.; Osswald, M.; Wick, W.; Winkler, F.] Univ Heidelberg Hosp, Neurol Clin, Heidelberg, Germany. [Liao, Y.; Osswald, M.; Wick, W.; Winkler, F.] Univ Heidelberg Hosp, Natl Ctr Tumor Dis, Heidelberg, Germany. [Berghoff, A. S.; Ilhan-Mutlu, A.] Med Univ Vienna, Dept Med 1, Clin Div Oncol, Vienna, Austria. [Berghoff, A. S.; Ilhan-Mutlu, A.] Med Univ Vienna, Vienna, Austria. [Gil, B.; Steeg, P.] NCI, Womens Malignancies Branch, NIH, Bethesda, MD 20892 USA. [Gil, B.; Steeg, P.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. [Gil, B.; Steeg, P.] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. [Gil, B.; Steeg, P.] NCI, Lab Anim Sci Program, SAIC Frederick, NIH, Frederick, MD 21701 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 OCT PY 2016 VL 18 SU 4 MA OS7.1 BP 15 EP 16 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DZ9MT UT WOS:000386200200053 ER PT J AU Mankodi, A Bishop, CA Auh, S Newbould, RD Fischbeck, KH Janiczek, RL AF Mankodi, Ami Bishop, Courtney A. Auh, Sungyoung Newbould, Rexford D. Fischbeck, Kenneth H. Janiczek, Robert L. TI Quantifying disease activity in fatty-infiltrated skeletal muscle by IDEAL-CPMG in Duchenne muscular dystrophy SO NEUROMUSCULAR DISORDERS LA English DT Article DE Duchenne muscular dystrophy; Magnetic resonance imaging; IDEAL-CPMG; Skeletal muscle; Apparent fat fraction; Fatty degeneration; T-2 relaxation times; Water T-2 ID STIMULATED ECHO COMPENSATION; TRANSVERSE RELAXOMETRY; QUANTIFICATION METHODS; NATURAL-HISTORY; WATER; MRI; PROGRESSION; BOYS; MULTICENTER; ACCURACY AB The purpose of this study was to explore the use of iterative decomposition of water and fat with echo asymmetry and least-squares estimation Carr-Purcell-Meiboom-Gill (IDEAL-CPMG) to simultaneously measure skeletal muscle apparent fat fraction and water T-2 (T-2,T-w) in patients with Duchenne muscular dystrophy (DMD). In twenty healthy volunteer boys and thirteen subjects with DMD, thigh muscle apparent fat fraction was measured by Dixon and IDEAL-CPMG, with the IDEAL-CPMG also providing T-2,T-w as a measure of muscle inflammatory activity. A subset of subjects with DMD was followed up during a 48-week clinical study. The study was in compliance with the Patient Privacy Act and approved by the Institutional Review Board. Apparent fat fraction in the thigh muscles of subjects with DMD was significantly increased compared to healthy volunteer boys (p < 0.001). There was a strong correlation between Dixon and IDEAL-CPMG apparent fat fraction. Muscle T-2,T-w measured by IDEAL-CPMG was independent of changes in apparent fat fraction. Muscle T-2,T-w was higher in the biceps femoris and vastus lateralis muscles of subjects with DMD (p < 0.05). There was a strong correlation (p < 0.004) between apparent fat fraction in all thigh muscles and six-minute walk distance (6MWD) in subjects with DMD. IDEAL-CPMG allowed independent and simultaneous quantification of skeletal muscle fatty degeneration and disease activity in DMD. IDEAL-CPMG apparent fat fraction and T-2,T-w may be useful as biomarkers in clinical trials of DMD as the technique disentangles two competing biological processes. 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 [Mankodi, Ami; Auh, Sungyoung; Fischbeck, Kenneth H.] NINDS, Neurogenet Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Bishop, Courtney A.; Newbould, Rexford D.] Hammersmith Hosp, Imanova Ctr Imaging Sci, London W12 0NN, England. [Janiczek, Robert L.] GlaxoSmithKline, Expt Med Imaging, Expt Med Unit, Middlesex UB11 1BT, England. RP Mankodi, A (reprint author), NINDS, Hereditary Muscle Dis Unit, Neurogenet Branch, NIH, 35 Convent Dr,Bldg 35,Room 2A-1002, Bethesda, MD 20892 USA. EM Ami.Mankodi@nih.gov FU Intramural NIH HHS [Z99 NS999999] NR 31 TC 1 Z9 1 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 EI 1873-2364 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2016 VL 26 IS 10 BP 650 EP 658 DI 10.1016/j.nmd.2016.07.013 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA EA2FL UT WOS:000386408100003 PM 27593185 ER PT J AU Goldstein, DS Holmes, C Sullivan, P Jinsmaa, Y Kopin, IJ Sharabi, Y AF Goldstein, David S. Holmes, Courtney Sullivan, Patricia Jinsmaa, Yunden Kopin, Irwin J. Sharabi, Yehonatan TI Elevated cerebrospinal fluid ratios of cysteinyl-dopamine/3,4-dihydroxyphenylacetic acid in parkinsonian synucleinopathies SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Parkinson disease; Multiple system atrophy; Aldehyde dehydrogenase ID MULTIPLE SYSTEM ATROPHY; DOPAMINE METABOLITE 3,4-DIHYDROXYPHENYLACETALDEHYDE; NEUROGENIC ORTHOSTATIC HYPOTENSION; ALDEHYDE DEHYDROGENASE-ACTIVITY; PURE AUTONOMIC FAILURE; ALPHA-SYNUCLEIN; MONOAMINE-OXIDASE; PC12 CELLS; MITOCHONDRIAL DYSFUNCTION; REACTIVE INTERMEDIATE AB Introduction: There is intense interest in identifying cerebrospinal fluid (CSF) biomarkers of Parkinson's disease (PD), both for early diagnosis and to track effects of putative treatments. Nigrostriatal dopamine depletion characterizes PD. Predictably, CSF levels of 3,4-dihydroxyphenylacetic acid (DOPAC), the main neuronal metabolite of dopamine, are decreased in PD, even in patients with recent onset of the movement disorder. Whether low CSF DOPAC is associated specifically with parkinsonism has been unclear. In the neuronal cytoplasm dopamine undergoes not only enzymatic oxidation to form DOPAC but also spontaneous oxidation to form 5-S-cysteinyl-dopamine (Cys-DA). Theoretically, oxidative stress or decreased activity of aldehyde dehydrogenase (ALDH) in the residual nigrostriatal dopaminergic neurons would increase CSF Cys-DA levels with respect to DOPAC levels. PD, parkinsonian multiple system atrophy (MSA-P), and pure autonomic failure (PAF) are synucleinopathies; however, PAF does not entail parkinsonism. We examined whether an elevated Cys-DA/DOPAC ratio provides a specific biomarker of parkinsonism in synucleinopathy patients. Methods: CSF catechols were assayed in PD (n = 24), MSA-P (n = 32), PAF (n = 18), and control subjects (n = 32). Results: Compared to controls, CSF DOPAC was decreased in PD and MSA-P (p < 0.0001 each). In both diseases Cys-DA/DOPAC ratios averaged more than twice control (0.14 +/- 0.02 and 0.13 +/- 0.02 vs. 0.05 +/- 0.01, p < 0.0001 each), whereas in PAF the mean Cys-DA/DOPAC ratio was normal (0.05 +/- 0.01). Conclusions: CSF Cys-DA/DOPAC ratios are substantially increased in PD and MSA-P and are normal in PAF. Thus, in synucleinopathies an elevated CSF Cys-DA/DOPAC ratio seems to provide a specific biomarker of parkinsonism. Published by Elsevier Ltd. C1 [Goldstein, David S.; Holmes, Courtney; Sullivan, Patricia; Jinsmaa, Yunden; Kopin, Irwin J.; Sharabi, Yehonatan] NINDS, Clin Neurocardiol Sect, NIH, 10 Ctr Dr MSC 1620,Bldg 10 Room 5N220, Bethesda, MD 20892 USA. [Sharabi, Yehonatan] Tel Aviv Univ, Tel Hashomer Affiliated Sackler Fac Med, Sheba Med Ctr, Hypertens Unit, IL-69978 Tel Aviv, Israel. RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, 10 Ctr Dr MSC 1620,Bldg 10 Room 5N220, Bethesda, MD 20892 USA. EM goldsteind@ninds.nih.gov FU Intramural Research Program of the NIH, NINDS FX This research was supported by the Intramural Research Program of the NIH, NINDS. NR 53 TC 1 Z9 1 U1 1 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 OCT PY 2016 VL 31 BP 79 EP 86 DI 10.1016/j.parkreldis.2016.07.009 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA EA1AG UT WOS:000386320100013 PM 27474472 ER PT J AU Lin, YH Brown, JA DiMartino, C Dahms, I Salem, N Hibbeln, JR AF Lin, Yu-Hong Brown, James A. DiMartino, Carmine Dahms, Irina Salem, Norman, Jr. Hibbeln, Joseph R. TI Differences in long chain polyunsaturates composition and metabolism in male and female rats SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article DE Essential fatty acid; Alpha-linolenic acid; Linoleic acid; DHA; DPA; Omega-3; Omega-6; Gender; Stable isotope; GC/MS ID ALPHA-LINOLENIC ACID; DOCOSAHEXAENOIC ACID; FATTY-ACIDS; GONADAL-HORMONES; SEX-DIFFERENCES; GENDER-DIFFERENCES; ARACHIDONIC-ACID; LIVER MICROSOMES; METHYL-ESTERS; FISH-OIL AB Human studies and some animal work have shown more docosahexaenoic acid (DHA) and arachidonic acid (ARA) was accumulated or converted from precursors in females compared to males. This study explored in-depth the effect of gender on fatty acid composition and polyunsaturated fatty acid metabolism in rats fed one of two well-defined diets containing 10% total fat. One diet contained 15% of linoleic acid (LA) and 3% of alpha-linolenic acid (ALA) of the total fatty acids (LA+ALA diet), while the other diet contained 15% LA and 0.05% ALA (LA diet). At the age of 20 weeks, all animals were orally administered a single dose of a mixture of deuterium-labeled LA and ALA. Caudal venous blood was then drawn at 0, 2, 4, 8, 12, 24, 48, 96 and 168 h. The concentrations of the deuterated precursors and their metabolites in plasma total lipids were quantified by GC/MS negative chemical ionization. Endogenous fatty acids were quantified by GC/FID analysis. When expressed as the percentage of oral dosage, female rats accumulated more precursors and more products, deuterated DHA and deuterated n-6 docosapentaenoic acid (H-2(5)-DPAn-6), in plasma than did male rats in both the LA+ALA diet and the LA diet. For the endogenous non-labeled PUFA, greater concentrations of DHA and DPAn-6 were similarly observed in female rats compared to males within each diet. A lower concentration of non-labeled ARA was observed only in female rats fed the LA+ALA diet. In summary, greater endogenous and exogenous DHA and DPAn-6 was observed in female rat plasma and this was independent of dietary ALA status. Published by Elsevier Ltd. C1 [Lin, Yu-Hong; Brown, James A.; DiMartino, Carmine; Hibbeln, Joseph R.] NIAAA, Sect Nutr Neurosci, LMBB, NIH, Bethesda, MD 20892 USA. [Dahms, Irina; Salem, Norman, Jr.] DSM Nutr Prod LLC, Nutr Lipids, Columbia, MD USA. RP Lin, YH (reprint author), NIAAA, Sect Nutr Neurosci, LMBB, NIH, Bethesda, MD 20892 USA. EM yuhong.lin@nih.gov FU Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism, NIH, United States [Z99 AA999999] FX The authors wish to acknowledge Dr. Lee Chedester and Dr. Raouf Kechrid for their expert assistance with the animal work. This project was funded by the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism, NIH, United States (Grant no. Z99 AA999999). NR 46 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0952-3278 EI 1532-2823 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD OCT PY 2016 VL 113 BP 19 EP 27 DI 10.1016/j.plefa.2016.08.008 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA EA2ER UT WOS:000386406100003 PM 27720036 ER PT J AU Quinn, G Vadaparampil, S Kanetsky, P Simmons, V Hudson, J Sutton, S Wheldon, C Sanchez, J Schabath, M AF Quinn, Gwendolyn Vadaparampil, Susan Kanetsky, Peter Simmons, Vani Hudson, Janella Sutton, Steven Wheldon, Christopher Sanchez, Julian Schabath, Matthew TI Sexual and Gender Minorities Cancer Screening and Health Behaviours SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Quinn, Gwendolyn; Vadaparampil, Susan; Kanetsky, Peter; Simmons, Vani; Hudson, Janella; Sutton, Steven; Sanchez, Julian; Schabath, Matthew] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Wheldon, Christopher] NCI, 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2016 VL 25 IS SP. S3 MA 141 BP 47 EP 47 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA DZ6AA UT WOS:000385942700100 ER PT J AU Bell, C Weaver, M Dickens, D Diver, J Smythe, E Iacoboni, A Hinds, P AF Bell, Cynthia Weaver, Meaghann Dickens, David Diver, Jessica Smythe, Elizabeth Iacoboni, Alyssa Hinds, Pamela TI Assessing Adolescent and Young Adult Acceptability of a Preliminary Instrument Measuring Readiness to Engage in End-of-Life Discussions within Clinical Settings SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Bell, Cynthia] Wayne State Univ, Detroit, MI USA. [Diver, Jessica] NIH, Washington, DC USA. [Dickens, David; Iacoboni, Alyssa] Helen DeVos Childrens Hosp, Grand Rapids, MI USA. [Smythe, Elizabeth] Childrens Hosp Michigan, Detroit, MI 48201 USA. [Hinds, Pamela] Childrens Natl Hlth Syst, Washington, DC USA. [Weaver, Meaghann] Childrens Hosp & Med Ctr, Pediat Palliat Care Program, Omaha, NE 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2016 VL 25 IS SP. S3 MA 514 BP 171 EP 171 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA DZ6AA UT WOS:000385942700387 ER PT J AU Aziz, N Rahman, A AF Aziz, Noreen Rahman, A. TI Lifestyle Health Behavior Interventions among Long Term Cancer Survivors SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 [Aziz, Noreen] NIH, Bldg 10, Bethesda, MD 20892 USA. [Rahman, A.] Univ Maryland, College Pk, MD 20742 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 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT PY 2016 VL 25 IS SP. S3 MA 594 BP 189 EP 189 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA DZ6AA UT WOS:000385942700432 ER PT J AU Louis, GMB Sapra, KJ Barr, DB Lu, ZH Sundaram, R AF Louis, Germaine M. Buck Sapra, Katherine J. Barr, Dana Boyd Lu, Zhaohui Sundaram, Rajeshwari TI Preconception perfluoroalkyl and polyfluoroalkyl substances and incident pregnancy loss, LIFE Study SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE Cohort; Epidemiology; Miscarriage; Perfluoroalkyl; Perfluoroalkyl acids; Polyfluoroalkyl; Pregnancy loss; Reproductive toxicity ID PERFLUOROOCTANOIC ACID EXPOSURE; HUMAN SEMEN QUALITY; PERFLUORINATED CHEMICALS; SERUM-LEVELS; TIME; WOMEN; PERFLUOROCHEMICALS; FERTILITY; SULFONATE; TOXICITY AB Equivocal findings are reported for perfluoroalkyl and polyfluoroalkyl substances (PFASs) and self-reported pregnancy loss. We prospectively assessed PFASs and pregnancy loss in a cohort comprising 501 couples recruited preconception and followed daily through 7 post-conception weeks. Seven PFAS5 were quantified: 2-N-ethyl-perfluorooctane sulfonamide acetate (Et-PFOSA-AcOH); 2-N-methyl-perfluorooctane sulfonamido acetate (Me-PFOSA-AcOH); perfluorodecanoate (PFDeA); perfluorononanoate (PFNA); perfluorooctane sulfonamide (PFOSA); perfluorooctane sulfonate (PFOS); and perfluorooctanoate (PFOA). Women used home pregnancy test kits. Loss denoted conversion from a positive to a negative pregnancy test, onset of menses or clinical confirmation (n = 98; 28%). Chemicals were log transformed and rescaled by their standard deviations to estimate adjusted hazard ratios (HRs) and 95% confidence intervals. No significantly elevated HRs were observed for any PFASs suggesting no association with loss: Et-PFOSA-AcOH (1.04; 0.87, 1.23), Me-PFOSA-AcOH (0.79; 0.61, 1.00; p < 0.05), PFDeA (0.83; 0.66, 1.04), PFNA (0.86; 0.70, 1.06), PFOSA (0.74; 0.50, 1.09), PFOS (0.81; 0.65, 1.00), and PFOA (0.93; 0.75, 1.16). Published by Elsevier Inc. C1 [Louis, Germaine M. Buck; Sapra, Katherine J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Off Director, Div Intramural Populat Hlth Res, Rockville, MD USA. [Barr, Dana Boyd] Emory Univ, Rollins Sch Publ Hlth, Dept Environm Hlth, Atlanta, GA 30322 USA. [Lu, Zhaohui] Glotech Inc, Rockville, MD USA. [Sundaram, Rajeshwari] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Biostat & Bioinformat Branch, Rockville, MD USA. RP Louis, GMB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Off Director, Div Intramural Populat Hlth Res, Rockville, MD USA. EM louisg@mail.nih.gov OI Buck Louis, Germaine/0000-0002-1774-4490; Sundaram, Rajeshwari/0000-0002-6918-5002 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development [N01-HD-3-3355, N01-HD-3-3356, NOH-HD-3-3358] FX Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (#N01-HD-3-3355; N01-HD-3-3356; NOH-HD-3-3358). We acknowledge the technical assistance of Antonia Calafat, Division of Laboratory Sciences, Centers for Disease Control and Prevention who performed the analytic chemistry work under a Memo of Understanding with the NICHD. NR 46 TC 0 Z9 0 U1 5 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD OCT PY 2016 VL 65 BP 11 EP 17 DI 10.1016/j.reprotox.2016.06.011 PG 7 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA DZ6RZ UT WOS:000385990900002 PM 27319395 ER PT J AU Hessel, EVS Ezendam, J van Broekhuizen, FA Hakkert, B DeWitt, J Granum, B Guzylack, L Lawrence, BP Penninks, A Rooney, AA Piersma, AH van Loveren, H AF Hessel, Ellen V. S. Ezendam, Janine van Broekhuizen, Fleur A. Hakkert, Betty DeWitt, Jamie Granum, Berit Guzylack, Laurence Lawrence, B. Paige Penninks, Andre Rooney, Andrew A. Piersma, Aldert H. van Loveren, Henk TI Assessment of recent developmental immunotoxicity studies with bisphenol A in the context of the 2015 EFSA t-TDI SO REPRODUCTIVE TOXICOLOGY LA English DT Article ID INNER-CITY CHILDREN; PRENATAL EXPOSURE; ASTHMA; INFLAMMATION; ADULTHOOD; ALLERGY; RISK; MICE AB Humans are exposed to bisphenol A (BPA) mainly through the diet, air, dust, skin contact and water. There are concerns about adverse health effects in humans due to exposure to bisphenol A (BPA). The European Food Safety Authority (EFSA) has extensively reviewed the available literature to establish a temporary Tolerable Daily Intake (t-TDI). This exposure level was based on all available literature published before the end of 2012. Since then, new experimental animal studies have emerged, including those that identified effects of BPA on the immune system after developmental exposure. These studies indicate that developmental immunotoxicity might occur at lower dose levels than previously observed and on which the current EFSA t-TDI is based. The Dutch National Institute for Public Health and the Environment (RIVM) organized an expert workshop in September 2015 to consider recently published studies on the developmental immunotoxicity of bisphenol A (BPA). Key studies were discussed in the context of other experimental studies. The workshop concluded that these new experimental studies provide credible evidence for adverse immune effects after developmental exposure to BPA at 5 mu g/kg BW/day from gestation day 15 to postnatal day 21. Supportive evidence for adverse immune effects in similar dose ranges was obtained from other publications that were discussed during the workshop. The dose level associated with adverse immune effects is considerably lower than the dose used by EFSA for deriving the t-TDI. The workshop unanimously concluded that the current EFSA t-TDI warrants reconsideration in the context of all currently available data. (C) 2016 Elsevier Inc. All rights reserved. C1 [Hessel, Ellen V. S.; Ezendam, Janine; Piersma, Aldert H.; van Loveren, Henk] Natl Inst Publ Hlth & Environm RIVM, Ctr Hlth Protect, Bilthoven, Netherlands. [van Broekhuizen, Fleur A.; Hakkert, Betty] Natl Inst Publ Hlth & Environm RIVM, Ctr Safety Subst & Prod, Bilthoven, Netherlands. [DeWitt, Jamie] East Carolina Univ, Dept Pharmacol & Toxicol, Greenville, NC USA. [Granum, Berit] Norwegian Inst Publ Hlth, Dept Toxicol & Risk Assessment, Oslo, Norway. [Guzylack, Laurence] Univ Toulouse, Dept Intestinal Dev Xenobiot & Immunotoxicol, INRA, Res Ctr Food Toxicol Toxalim, Toulouse, France. [Lawrence, B. Paige] Univ Rochester, Sch Med & Dent, Dept Environm Med, Rochester, NY USA. [Lawrence, B. Paige] Univ Rochester, Sch Med & Dent, Dept Microbiol & Immunol, Rochester, NY 14642 USA. [Penninks, Andre] TNO Triskel BV, Dept Toxicol & Risk Assessment, Zeist, Netherlands. [Rooney, Andrew A.] NIEHS, Natl Toxicol Program, Off Hlth Assessment & Translat, POB 12233, Res Triangle Pk, NC 27709 USA. [Piersma, Aldert H.] Univ Utrecht, Inst Risk Assessment Sci, Fac Vet, Utrecht, Netherlands. [van Loveren, Henk] Maastricht Univ, Dept Toxicogen, Maastricht, Netherlands. RP Piersma, AH (reprint author), Natl Inst Publ Hlth & Environm RIVM, Ctr Hlth Protect, Bilthoven, Netherlands. EM aldert.piersma@rivm.nl OI DeWitt, Jamie/0000-0002-0440-4059 NR 21 TC 0 Z9 0 U1 6 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD OCT PY 2016 VL 65 BP 448 EP 456 DI 10.1016/j.reprotox.2016.06.020 PG 9 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA DZ6RZ UT WOS:000385990900045 PM 27352639 ER PT J AU McFadden, WC Jaffe, AE Ye, TZ Paltan-Ortiz, JD Hyde, TM Kleinman, JE AF McFadden, Whitney C. Jaffe, Andrew E. Ye, Tianzhang Paltan-Ortiz, Jose D. Hyde, Thomas M. Kleinman, Joel E. TI Assessment of genetic risk for distribution of total interstitial white matter neurons in dorsolateral prefrontal cortex: role in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Interstitial white matter neurons; Schizophrenia; Dorsolateral prefrontal cortex; Postmortem brain ID DENSITY; EXPRESSION; BRAINS C1 [McFadden, Whitney C.; Paltan-Ortiz, Jose D.; Kleinman, Joel E.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis, Div Intramural Res Programs,NIH, Bethesda, MD 20892 USA. [Jaffe, Andrew E.; Ye, Tianzhang; Hyde, Thomas M.; Kleinman, Joel E.] Lieber Inst Brain Dev, Rangos Bldg,Johns Hopkins Med Campus, Baltimore, MD 21205 USA. RP McFadden, WC (reprint author), Mt Sinai Hosp, Dept Psychiat, One Gustave L Levy Pl, New York, NY 10029 USA. FU NIH; Intramural Research Program of the NIH, NIMH FX This research was made possible through 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 Leona M. and Harry B. Helmsley Charitable Trust, and the Howard Hughes Medical Institute, as well as other private donors. This research was supported in part by the Intramural Research Program of the NIH, NIMH. NR 17 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2016 VL 176 IS 2-3 BP 141 EP 143 DI 10.1016/j.schres.2016.04.007 PG 3 WC Psychiatry SC Psychiatry GA DX1LZ UT WOS:000384130200009 PM 27237599 ER PT J AU Luo, Z Dauter, Z AF Luo, Zhipu Dauter, Zbigniew TI Detection of twinning in macromolecular crystallography SO ZEITSCHRIFT FUR KRISTALLOGRAPHIE-CRYSTALLINE MATERIALS LA English DT Article DE macromolecular crystallography; merohedral twinning; pseudo-merohedral twinning; twinning fraction; twinning tests ID INTENSITY STATISTICS; STRUCTURE REFINEMENT; CRYSTAL-STRUCTURE; PROTEIN CRYSTALS; TWINS; MEROHEDRY AB The merohedrally or pseudo-merohedrally twinned crystals cannot be identified during diffraction pattern inspection at the stage of data collection. Several methods for identifying twinning and estimating the twin fraction are suitable for macromolecular crystals, and all are based on the statistical properties of the measured diffraction intensities. They can be based on either the overall statistical properties of the measured reflection intensities or on the comparison of reflection intensities related by the twinning operation. The application of various tests for identification of twinning and estimation of twinning fraction is discussed, with examples of diffraction data from the Protein Data Bank. Twinning makes the solution of crystal structures more difficult, but once initially solved, the atomic models can be properly refined by the existing programs. C1 [Luo, Zhipu; Dauter, Zbigniew] NCI, Argonne Natl Lab, Synchrotron Radiat Res Sect, Argonne, IL 60439 USA. RP Dauter, Z (reprint author), NCI, Argonne Natl Lab, Synchrotron Radiat Res Sect, Argonne, IL 60439 USA. EM dauter@anl.gov FU Intramural Research Program of the National Cancer Institute FX This work was supported by the Intramural Research Program of the National Cancer Institute. NR 35 TC 0 Z9 0 U1 1 U2 1 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 2194-4946 EI 2196-7105 J9 Z KRIST-CRYST MATER JI Z. Krist.-Cryst. Mater. PD OCT PY 2016 VL 231 IS 10 SI SI BP 561 EP 571 DI 10.1515/zkri-2016-1946 PG 11 WC Crystallography SC Crystallography GA DZ7NB UT WOS:000386051600004 ER PT J AU Lin, J Chen, XY Huang, P AF Lin, Jing Chen, Xiaoyuan Huang, Peng TI Graphene-based nanomaterials for bioimaging SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE Graphene; Graphene oxide; Reduced graphene oxide; Graphene quantum dots; Photoacoustic imaging; PET/SPECT; MRI; Bioimaging ID ENHANCED RAMAN-SCATTERING; NEAR-INFRARED WINDOW; MESOPOROUS SILICA NANOPARTICLES; GUIDED PHOTOTHERMAL THERAPY; RAY-COMPUTED-TOMOGRAPHY; MRI CONTRAST AGENTS; DRUG-DELIVERY; IN-VIVO; NANO-GRAPHENE; QUANTUM DOTS AB Graphene-based nanomaterials, due to their unique physicochemical properties, versatile surface functionalization, ultra-high surface area, and good biocompatibility, have attracted considerable interest in biomedical applications such as biosensors, drug delivery, bioimaging, theranostics, and so on. In this review, we will summarize the current advances in bioimaging of graphene-based nanomaterials, including graphene, graphene oxide (GO), reduced graphene oxide (rGO), graphene quantum dots (GQDs), and their derivatives. There are two methods to synthesize graphene-based nanomaterials: in situ synthesis and binding method. We will highlight the molecular imaging modalities including optical imaging (fluorescence (FL), two-photon FL, and Raman imaging), PET/SPECT (positron emission tomography/single photon emission computed tomography), MM (magnetic resonance imaging), PAI (photoacoustic imaging), CT (computed tomography), and multimodal imaging. In the end, we will elaborate on the prospects and challenges of their future bioimaging applications. Published by Elsevier B.V. C1 [Lin, Jing; Huang, Peng] Shenzhen Univ, Sch Med, Dept Biomed Engn, Guangdong Key Lab Biomed Measurements & Ultrasoun, Shenzhen 518060, Peoples R China. [Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. RP Huang, P (reprint author), Shenzhen Univ, Sch Med, Dept Biomed Engn, Guangdong Key Lab Biomed Measurements & Ultrasoun, Shenzhen 518060, Peoples R China.; Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov; peng.huang@szu.edu.cn RI Huang, Peng/R-2480-2016 OI Huang, Peng/0000-0003-3651-7813 FU National Science Foundation of China [51573096, 81401465]; Intramural Research Program (IRP) of the NIBIB; NIH FX This work was supported by the National Science Foundation of China (51573096, 81401465), and the Intramural Research Program (IRP) of the NIBIB, NIH. NR 128 TC 6 Z9 6 U1 108 U2 108 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X EI 1872-8294 J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD OCT 1 PY 2016 VL 105 BP 242 EP 254 DI 10.1016/j.addr.2016.05.013 PN B PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DZ1LW UT WOS:000385600900009 PM 27233213 ER PT J AU Xuan, ZM Naimi, TS Kaplan, MS Bagge, CL Few, LR Maisto, S Saitz, R Freeman, R AF Xuan, Ziming Naimi, Timothy S. Kaplan, Mark S. Bagge, Courtney L. Few, Lauren R. Maisto, Stephen Saitz, Richard Freeman, Robert TI Alcohol Policies and Suicide: A Review of the Literature SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Review DE Alcohol Policies; Suicide; Blood Alcohol Content; Critical Review ID LEGAL DRINKING AGE; DEATH REPORTING SYSTEM; TIME-SERIES ANALYSIS; UNITED-STATES; PSYCHIATRIC-DISORDERS; YOUTH SUICIDE; RISK-FACTORS; MORTALITY; TAX; US AB Both intoxication and chronic heavy alcohol use are associated with suicide. There is extensive population-level evidence linking per capita alcohol consumption with suicide. While alcohol policies can reduce excessive alcohol consumption, the relationship between alcohol policies and suicide warrants a critical review of the literature. This review summarizes the associations between various types of alcohol policies and suicide, both in the United States and internationally, as presented in English-language literature published between 1999 and 2014. Study designs, methodological challenges, and limitations in ascertaining the associations are discussed. Because of the substantial between-states variation in alcohol policies, U.S.-based studies contributed substantially to the literature. Repeated cross-sectional designs at both the ecological level and decedent level were common among U.S.-based studies. Non-U.S. studies often used time series data to evaluate pre-post comparisons of a hybrid set of policy changes. Although inconsistency remained, the published literature in general supported the protective effect of restrictive alcohol policies on reducing suicide as well as the decreased level of alcohol involvement among suicide decedents. Common limitations included measurement and selection bias and a focus on effects of a limited number of alcohol policies without accounting for other alcohol policies. This review summarizes a number of studies that suggest restrictive alcohol policies may contribute to suicide prevention on a general population level and to a reduction of alcohol involvement among suicide deaths. C1 [Xuan, Ziming; Saitz, Richard] Boston Univ, Dept Community Hlth Sci, Sch Publ Hlth, 801 Massachusetts Ave,Crosstown 443, Boston, MA 02118 USA. [Naimi, Timothy S.] Boston Med Ctr, Sect Gen Internal Med, Boston, MA USA. [Kaplan, Mark S.] Univ Calif Los Angeles, Sch Publ Affairs, Dept Social Welf, Los Angeles, CA USA. [Bagge, Courtney L.] Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, Jackson, MS 39216 USA. [Few, Lauren R.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Maisto, Stephen] Syracuse Univ, Dept Psychol, Syracuse, NY USA. [Freeman, Robert] NIAAA, NIH, Bethesda, MD USA. RP Xuan, ZM (reprint author), Boston Univ, Dept Community Hlth Sci, Sch Publ Hlth, 801 Massachusetts Ave,Crosstown 443, Boston, MA 02118 USA. EM zxuan@bu.edu FU NIAAA NIH HHS [F32 AA023693, K05 AA016928, R01 AA020063, R01 AA021335, R01 AA021791, R01 AA023376, U01 AA020784] NR 71 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 OCT PY 2016 VL 40 IS 10 BP 2043 EP 2055 DI 10.1111/acer.13203 PG 13 WC Substance Abuse SC Substance Abuse GA DZ0PT UT WOS:000385542900002 PM 27618526 ER PT J AU Williams, EC Hahn, JA Saitz, R Bryant, K Lira, MC Samet, JH AF Williams, Emily C. Hahn, Judith A. Saitz, Richard Bryant, Kendall Lira, Marlene C. Samet, Jeffrey H. TI Alcohol Use and Human Immunodeficiency Virus (HIV) Infection: Current Knowledge, Implications, and Future Directions SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Review DE Alcohol; Alcohol Use; Substance Use; HIV; HIV-Related Comorbidities ID RANDOMIZED CONTROLLED-TRIAL; ACTIVE ANTIRETROVIRAL THERAPY; INTERACTIVE TOXICITY BELIEFS; NUTRITION EXAMINATION SURVEY; SYSTEMIC IMMUNE ACTIVATION; MULTICENTER AIDS COHORT; HEALTH-CARE-UTILIZATION; ALL-CAUSE MORTALITY; SUB-SAHARAN AFRICA; ILLICIT DRUG-USE AB Alcohol use is common among people living with human immunodeficiency virus (HIV). In this narrative review, we describe literature regarding alcohol's impact on transmission, care, coinfections, and comorbidities that are common among people living with HIV (PLWH), as well as literature regarding interventions to address alcohol use and its influences among PLWH. This narrative review identifies alcohol use as a risk factor for HIV transmission, as well as a factor impacting the clinical manifestations and management of HIV. Alcohol use appears to have additive and potentially synergistic effects on common HIV-related comorbidities. We find that interventions to modify drinking and improve HIV-related risks and outcomes have had limited success to date, and we recommend research in several areas. Consistent with Office of AIDS Research/National Institutes of Health priorities, we suggest research to better understand how and at what levels alcohol influences comorbid conditions among PLWH, to elucidate the mechanisms by which alcohol use is impacting comorbidities, and to understand whether decreases in alcohol use improve HIV-relevant outcomes. This should include studies regarding whether state-of-the-art medications used to treat common coinfections are safe for PLWH who drink alcohol. We recommend that future research among PLWH include validated self-report measures of alcohol use and/or biological measurements, ideally both. Additionally, subgroup variation in associations should be identified to ensure that the risks of particularly vulnerable populations are understood. This body of research should serve as a foundation for a next generation of intervention studies to address alcohol use from transmission to treatment of HIV. Intervention studies should inform implementation efforts to improve provision of alcohol-related interventions and treatments for PLWH in healthcare settings. By making further progress on understanding how alcohol use affects PLWH in the era of HIV as a chronic condition, this research should inform how we can mitigate transmission, achieve viral suppression, and avoid exacerbating common comorbidities of HIV and alcohol use and make progress toward the 90-90-90 goals for engagement in the HIV treatment cascade. C1 [Williams, Emily C.] Ctr Innovat Vet Ctr & Value Driven Care, Vet Hlth Adm VA Hlth Serv Res & Dev, Seattle, WA USA. [Williams, Emily C.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Hahn, Judith A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Hahn, Judith A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Saitz, Richard; Samet, Jeffrey H.] Boston Univ, Sch Publ Hlth, Dept Community Hlth Sci, Boston, MA USA. [Saitz, Richard; Lira, Marlene C.; Samet, Jeffrey H.] Boston Univ, Sch Med, Dept Med, CARE Unit,Sect Gen Internal Med,Boston Med Ctr, Boston, MA 02118 USA. [Bryant, Kendall] NIAAA, CHAART, NIH, Bethesda, MD USA. RP Samet, JH (reprint author), Boston Univ, Boston Med Ctr, Sch Med, 801 Massachusetts Ave,2nd Floor, Boston, MA 02118 USA.; Samet, JH (reprint author), Boston Univ, Boston Med Ctr, Sch Publ Hlth, 801 Massachusetts Ave,2nd Floor, Boston, MA 02118 USA. EM jsamet@bu.edu FU HSRD VA [IK2 HX001161]; NIAAA NIH HHS [U24 AA020778, K24 AA022586, U01 AA020776, U01 AA020780, U01 AA020784] NR 285 TC 0 Z9 0 U1 7 U2 7 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 OCT PY 2016 VL 40 IS 10 BP 2056 EP 2072 DI 10.1111/acer.13204 PG 17 WC Substance Abuse SC Substance Abuse GA DZ0PT UT WOS:000385542900003 PM 27696523 ER PT J AU Vatsalya, V Song, M Schwandt, ML Cave, MC Barve, SS George, DT Ramchandani, VA McClain, CJ AF Vatsalya, Vatsalya Song, Ming Schwandt, Melanie L. Cave, Matthew C. Barve, Shirish S. George, David T. Ramchandani, Vijay A. McClain, Craig J. TI Effects of Sex, Drinking History, and Omega-3 and Omega-6 Fatty Acids Dysregulation on the Onset of Liver Injury in Very Heavy Drinking Alcohol-Dependent Patients SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol; Sex; Heavy Drinking Markers; Fatty Acids; Liver Injury ID DISEASE; INFLAMMATION; SUSCEPTIBILITY; STEATOSIS; MEDIATORS AB BackgroundHeavy alcohol consumption frequently causes liver inflammation/injury, and certain fatty acids (FAs) may be involved in this liver pathology. In this study, we evaluated the association of heavy drinking and the changes in the FA levels involved in the -6 (pro-inflammatory) and -3 (anti-inflammatory) state in alcohol-dependent (AD) patients who had no clinical manifestations of liver injury. We aimed to identify sex-based differences in patients with mild or no biochemical evidence of liver injury induced by heavy drinking. MethodsA total of 114 heavy drinking AD female and male patients aged 21 to 65years without clinical manifestations of liver injury, who were admitted to an alcohol dependence treatment program, were grouped by the alanine aminotransferase (ALT) levels: 40 IU/l, as no liver injury (GR.1), and >40 IU/l, as mild liver injury (GR.2). Patients were actively drinking until the day of admission. Comprehensive metabolic panel, comprehensive FA panel, and drinking history data were evaluated. ResultsElevated ALT and aspartate aminotransferase (AST) showed close association with markers of heavy alcohol intake. In the patients with mild biochemical liver injury (GR.2), females showed significantly higher AST level than males. Significant association of AST and total drinks in past 90 days (TD90) in females, and AST and heavy drinking days in past 90 days (HDD90) in males was observed. The -6:-3 ratio showed a significant pro-inflammatory response only in females with mild liver injury (GR.2) when adjusted by drinking history marker, TD90. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were increased in males with liver injury, while females did not show any comparable rise in EPA; and DHA levels were lower. ConclusionsMeasures of heavy drinking, TD90 and HDD90, predicted changes in liver injury. Changes in the -3 and -6 FA levels and the -6:-3 ratio showed a pro-inflammatory shift in patients with biochemical liver injury with a significant effect in females. Changes in FAs involved in the inflammatory state may represent one mechanism for liver inflammation/injury in response to heavy alcohol drinking. C1 [Vatsalya, Vatsalya; Song, Ming; Cave, Matthew C.; Barve, Shirish S.; McClain, Craig J.] Univ Louisville, Dept Med, Sch Med, 505 S Hancock St CTR Room 521A, Louisville, KY 40202 USA. [Vatsalya, Vatsalya; Cave, Matthew C.; McClain, Craig J.] Robley Rex Vet Affairs Med Ctr, Louisville, KY USA. [Vatsalya, Vatsalya; Schwandt, Melanie L.; George, David T.; Ramchandani, Vijay A.] NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA. [Cave, Matthew C.; Barve, Shirish S.; McClain, Craig J.] Univ Louisville, Sch Med, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. RP Vatsalya, V (reprint author), Univ Louisville, Dept Med, Sch Med, 505 S Hancock St CTR Room 521A, Louisville, KY 40202 USA. EM vatsalya.vatsalya@louisville.edu OI Vatsalya, Vatsalya/0000-0001-6764-6891 FU Intramural NIH HHS [Z99 AA999999]; NIAAA NIH HHS [P50 AA024337, U01 AA021901, ZIA AA000213, ZIA AA000466]; NIGMS NIH HHS [P20 GM113226] NR 26 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 OCT PY 2016 VL 40 IS 10 BP 2085 EP 2093 DI 10.1111/acer.13197 PG 9 WC Substance Abuse SC Substance Abuse GA DZ0PT UT WOS:000385542900006 PM 27589090 ER PT J AU Wardell, JD Ramchandani, VA Hendershot, CS AF Wardell, Jeffrey D. Ramchandani, Vijay A. Hendershot, Christian S. TI Drinking Motives Predict Subjective Effects of Alcohol and Alcohol Wanting and Liking During Laboratory Alcohol Administration: A Mediated Pathway Analysis SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Subjective Response; Craving; Liking; Coping; Alcohol Challenge ID COLLEGE-STUDENTS; PSYCHOMETRIC SUPPORT; MOTIVATED DRINKERS; ACUTE TOLERANCE; FAMILY-HISTORY; BINGE DRINKING; EFFECTS SCALE; YOUNG-PEOPLE; MODEL; RESPONSES AB BackgroundMotivational models of alcohol use suggest that individual differences in sensitivity to the acute subjective effects of alcohol play an important role in motivational pathways to alcohol use. However, few studies have examined the link between drinking motives and subjective responses to alcohol. This study investigated the associations of coping and enhancement drinking motives with subjective stimulant and sedative effects during a laboratory alcohol administration session. We also examined whether stimulation and sedation following alcohol administration mediated the relationships between drinking motives and postalcohol ratings of alcohol wanting and liking. MethodsHeavy episodic drinkers (n=147, ages 19 to 25) at 2 sites participated in an intravenous alcohol administration session in which blood alcohol concentration was raised to a target of 80mg% over 20minutes. Participants completed measures of stimulation and sedation at baseline and 20minutes and also rated alcohol liking and wanting at 20minutes. Drinking motives and alcohol use were assessed during a previous laboratory visit. ResultsA path analysis controlling for baseline stimulation and sedation showed that enhancement motives were positively associated with postalcohol stimulation and negatively associated with postalcohol sedation. In contrast, coping motives were positively associated with postalcohol sedation. In turn, postalcohol stimulation, but not sedation, was associated with alcohol wanting and liking. Further, indirect pathways from enhancement motives to postalcohol wanting and liking mediated through postalcohol stimulation were statistically significant. Coping motives, on the other hand, were directly associated with increased postalcohol wanting and liking. ConclusionsThe results demonstrate that drinking motives are linked with individual differences in sensitivity to the effects of alcohol, which may serve as a mechanism underlying alcohol reinforcement and the motivation to consume more alcohol during a drinking episode. C1 [Wardell, Jeffrey D.; Hendershot, Christian S.] Ctr Addict & Mental Hlth, Campbell Family Mental Hlth Res Inst, Toronto, ON, Canada. [Ramchandani, Vijay A.] NIAAA, Sect Human Psychopharmacol, Div Intramural Clin & Biol Res, NIH, Bethesda, MD USA. [Hendershot, Christian S.] Ctr Addict & Mental Hlth, Inst Mental Hlth Policy Res, Toronto, ON, Canada. [Hendershot, Christian S.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [Hendershot, Christian S.] Univ Toronto, Dept Psychol, Toronto, ON, Canada. RP Hendershot, CS (reprint author), Ctr Addict & Mental Hlth, 100 Stokes St, Toronto, ON M6J 1H4, Canada. EM christian.hendershot@utoronto.ca FU NIAAA NIH HHS [R21 AA020304, P60 AA007611] NR 49 TC 0 Z9 0 U1 5 U2 5 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 OCT PY 2016 VL 40 IS 10 BP 2190 EP 2198 DI 10.1111/acer.13174 PG 9 WC Substance Abuse SC Substance Abuse GA DZ0PT UT WOS:000385542900016 PM 27527738 ER PT J AU Karlsson, C Aziz, AMA Rehman, F Pitcairn, C Barchiesi, R Barbier, E Wendel Hansen, M Gehlert, D Steensland, P Heilig, M Thorsell, A AF Karlsson, Camilla Aziz, Abdul Maruf Asif Rehman, Faazal Pitcairn, Caleb Barchiesi, Riccardo Barbier, Estelle Wendel Hansen, Mikaela Gehlert, Don Steensland, Pia Heilig, Markus Thorsell, Annika TI Melanin-Concentrating Hormone and Its MCH-1 Receptor: Relationship Between Effects on Alcohol and Caloric Intake SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Escalation; Reward; Motivation; Calorie Intake; Melanin-Concentrating Hormone Receptor-1 ID VOLUNTARY ETHANOL-CONSUMPTION; APPETITE REGULATION; NUCLEUS-ACCUMBENS; DRUG-ADDICTION; RAT-BRAIN; DOPAMINE; SYSTEM; REWARD; FOOD; OBESITY AB BackgroundReward and energy homeostasis are both regulated by a network of hypothalamic neuropeptide systems. The melanin-concentrating hormone (MCH) and its MCH-1 receptor (MCH1-R) modulate alcohol intake, but it remains unknown to what extent this reflects actions on energy balance or reward. Here, we evaluated the MCH1-R in regulation of caloric intake and motivation to consume alcohol in states of escalated consumption. MethodsRats had intermittent access (IA) to alcohol and were divided into high- and low-drinking groups. Food and alcohol consumption was assessed after administration of an MCH1-R antagonist, GW803430. Next, GW803430 was evaluated on alcohol self-administration in protracted abstinence induced by IA in high-drinking rats. Finally, the effect of GW803430 was assessed on alcohol self-administration in acute withdrawal in rats exposed to alcohol vapor. Gene expression of MCH and MCH1-R was measured in the hypothalamus and nucleus accumbens (NAc) in both acute and protracted abstinence. ResultsHigh-drinking IA rats consumed more calories from alcohol than chow and GW803430 decreased both chow and alcohol intake. In low-drinking rats, only food intake was affected. In protracted abstinence from IA, alcohol self-administration was significantly reduced by pretreatment with GW803430 and gene expression of both MCH and the MCH1-R were dysregulated in hypothalamus and NAc. In contrast, during acute withdrawal from vapor exposure, treatment with GW803430 did not affect alcohol self-administration, and no changes in MCH or MCH1-R gene expression were observed. ConclusionsOur data suggest a dual role of MCH and the MCH1-R in regulation of alcohol intake, possibly through mechanisms involving caloric intake and reward motivation. A selective suppression of alcohol self-administration during protracted abstinence by GW803430 was observed and accompanied by adaptations in gene expression of MCH and MCH1-R. Selective suppression of escalated consumption renders the MCH1-R an attractive target for treatment of alcohol use disorders. C1 [Karlsson, Camilla; Aziz, Abdul Maruf Asif; Barchiesi, Riccardo; Barbier, Estelle; Wendel Hansen, Mikaela; Heilig, Markus; Thorsell, Annika] Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden. [Rehman, Faazal; Pitcairn, Caleb] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. [Gehlert, Don] Eli Lilly & Co, Lilly Res Labs, CNS Res, Indianapolis, IN 46285 USA. [Steensland, Pia] Karolinska Inst, Clin Neurosci, Stockholm, Sweden. RP Karlsson, C (reprint author), Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden. EM camilla.s.karlsson@liu.se NR 37 TC 1 Z9 1 U1 5 U2 5 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 OCT PY 2016 VL 40 IS 10 BP 2199 EP 2207 DI 10.1111/acer.13181 PG 9 WC Substance Abuse SC Substance Abuse GA DZ0PT UT WOS:000385542900017 PM 27579857 ER PT J AU Patel, VS Sampat, V Espey, MG Sitapara, R Wang, HC Yang, XJ Ashby, CR Thomas, DD Mantell, LL AF Patel, Vivek S. Sampat, Vaishali Espey, Michael Graham Sitapara, Ravikumar Wang, Haichao Yang, Xiaojing Ashby, Charles R., Jr. Thomas, Douglas D. Mantell, Lin L. TI Ascorbic Acid Attenuates Hyperoxia-Compromised Host Defense against Pulmonary Bacterial Infection SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE hyperoxia; ascorbic acid; pneumonia; high-mobility group box 1 ID NF-KAPPA-B; VENTILATOR-ASSOCIATED PNEUMONIA; OXYGEN RADICAL PRODUCTION; CHROMATIN PROTEIN HMGB1; MOBILITY GROUP BOX-1; INDUCED LUNG INJURY; VITAMIN-C; OXIDATIVE STRESS; PSEUDOMONAS-AERUGINOSA; IN-VITRO AB Supraphysiological concentrations of oxygen (hyperoxia) can compromise host defense and increase susceptibility to bacterial infections, causing ventilator-associated pneumonia. The phagocytic activity of macrophages is impaired by hyperoxia-induced increases in the levels of reactive oxygen species (ROS) and extracellular high-mobility group box protein B1 (HMGB1). Ascorbic acid (AA), an essential nutrient and antioxidant, has been shown to be beneficial in various animal models of ROS-mediated diseases. The aim of this study was to determine whether AA could attenuate hyperoxia-compromised host defense and improve macrophage functions against bacterial infections. C57BL/6 male mice were exposed to hyperoxia (>= 98% O-2, 48 h), followed by intratracheal inoculation with Pseudomonas aeruginosa, and simultaneous intraperitoneal administration of AA. AA(50mg/kg) significantly improved bacterial clearance in the lungs and airways, and significantly reduced HMGB1 accumulation in the airways. The incubation of RAW 264.7 cells (a macrophage-like cell line) with AA (0-1,000 mu M) before hyperoxic exposure (95% O-2) stabilized the phagocytic activity of macrophages in a concentration-dependent manner. The AA-enhanced macrophage function was associated with significantly decreased production of intracellular ROS and accumulation of extracellular HMGB1. These data suggest that AA supplementation can prevent or attenuate the development of ventilator-associated pneumonia in patients receiving oxygen support. C1 [Patel, Vivek S.; Sampat, Vaishali; Sitapara, Ravikumar; Yang, Xiaojing; Ashby, Charles R., Jr.; Mantell, Lin L.] St Johns Univ, Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, 128 St Albert Hall,8000 Utopia Pkwy, Queens, NY 11439 USA. [Espey, Michael Graham] NCI, Bethesda, MD 20892 USA. [Wang, Haichao; Mantell, Lin L.] North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA. [Thomas, Douglas D.] Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, Chicago, IL USA. RP Mantell, LL (reprint author), St Johns Univ, Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, 128 St Albert Hall,8000 Utopia Pkwy, Queens, NY 11439 USA. EM lmantell@nshs.edu OI Wang, Haichao/0000-0002-0211-9000 FU National Heart, Lung, and Blood Institute [HL093708]; St. John's University FX This work was supported by National Heart, Lung, and Blood Institute grant HL093708 (L.L.M.) and a grant from St. John's University. NR 72 TC 0 Z9 0 U1 3 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1044-1549 EI 1535-4989 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD OCT 1 PY 2016 VL 55 IS 4 BP 511 EP 520 DI 10.1165/rcmb.2015-0310OC PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA DZ2DY UT WOS:000385653700007 PM 27120084 ER PT J AU Hunter, CM AF Hunter, Christine M. TI Understanding Diabetes and the Role of Psychology in Its Prevention and Treatment SO AMERICAN PSYCHOLOGIST LA English DT Article DE diabetes; treatment; prevention; biopsychosocial model; health psychology ID LIFE-STYLE INTERVENTION; EXCHANGE CLINIC REGISTRY; HEALTH BEHAVIOR-CHANGE; FUTURE-DIRECTIONS; YOUNG-CHILDREN; MENTAL-HEALTH; OBESE ADULTS; TYPE-1; PREVALENCE; MELLITUS AB Diabetes is a common, chronic, and costly condition that currently affects millions of individuals in the United States and worldwide with even greater numbers at high risk for developing the disease. Dramatic increases in diagnosed diabetes are projected for the decades to come meaning that most people will be affected by diabetes; either personally or through a family member. This article introduces the special issue of the American Psychologist focused on diabetes by providing an overview of the scope of diabetes and the importance of psychologists for improving disease management and quality of life. This includes an overview of the contributions of the behavioral and social sciences toward improved diabetes prevention and treatment. Finally, the article will point to opportunities for psychologists to close the gaps in the research, develop practice competencies, and increase training opportunities to meet the challenges of diabetes today and in the future. C1 [Hunter, Christine M.] NIDDK, Bethesda, MD 20892 USA. RP Hunter, CM (reprint author), NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, 6707 Democracy Blvd,Room 6071, Bethesda, MD 20892 USA. EM hunterchristine@niddk.nih.gov NR 79 TC 5 Z9 5 U1 16 U2 16 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X EI 1935-990X J9 AM PSYCHOL JI Am. Psychol. PD OCT PY 2016 VL 71 IS 7 SI SI BP 515 EP 525 DI 10.1037/a0040344 PG 11 WC Psychology, Multidisciplinary SC Psychology GA DZ0YV UT WOS:000385566500001 PM 27690481 ER PT J AU Lenis, YY Wang, XQ Tang, WJ Wu, GY Bazer, FW AF Lenis, Yasser Y. Wang, Xiaoqiu Tang, Wanjin Wu, Guoyao Bazer, Fuller W. TI Effects of agmatine on secretion of interferon tau and catecholamines and expression of genes related to production of polyamines by ovine trophectoderm cells SO AMINO ACIDS LA English DT Article DE Arginine; Agmatine; Polyamines; Trophectoderm cells; Interferon tau ID NITRIC-OXIDE SYNTHASE; SELECT NUTRIENTS; AMINO-ACIDS; ARGININE SUPPLEMENTATION; PERIIMPLANTATION PERIOD; MAMMALIAN CONCEPTUSES; DEVELOPMENTAL-CHANGES; SIGNALING PATHWAYS; EARLY-PREGNANCY; TUMOR-CELLS AB Embryonic survival requires histotrophic nutrition, including molecules secreted or transported into the uterine lumen by uterine epithelia. l-Arginine (Arg) is a common substrate for synthesis of nitric oxide, ornithine, proline, glutamate, creatinine, urea, polyamines and agmatine. Agmatine (Agm) is a product of arginine decarboxylation and it is a substrate for agmatinase for synthesis of putrescine and other polyamines in the ovine conceptus. Polyamines are essential for conceptus development. Therefore, this study compared effects of Arg and Agm on the behavior of ovine trophectoderm (oTr1) cells cultured in vitro. Arg, but not Agm, increased proliferation and migration of oTr1 cells, but neither Arg nor Agm affected cell adhesion. The total amount of IFNT in culture medium of oTr1 cells was increased by Arg, but Agm increased the IFNT production per oTr1 cell. Arg and Agm plus Arg decreased secretion of dopamine and norepinephrine by oTr1 cells. Agm upregulates expression of mRNAs SLC7A1, agmatinase and OAZ2 while the combination of Arg and Agm decreased expression of mRNAs for ODC1, SLC7A1, OAZ1 and OAZ3 by oTr1 cells. Although Agm does not stimulate proliferation, migration or adhesion of oTr1 cells or their secretion of catecholamines, Agm did increase transcription of SLC7A1, agmatinase and OAZ2 genes which would increase the capacity of oTr1 cells to produce polyamines. Collectively, our findings suggest a role for Arg and Agm in the regulation of transport of basic amino acids (including Arg), polyamine synthesis, and secretion of catecholamines by oTr1 cells. C1 [Lenis, Yasser Y.; Wang, Xiaoqiu; Tang, Wanjin; Wu, Guoyao; Bazer, Fuller W.] Texas A&M Univ, Dept Anim Sci, College Stn, TX 77843 USA. [Lenis, Yasser Y.; Wang, Xiaoqiu; Tang, Wanjin; Wu, Guoyao; Bazer, Fuller W.] Texas A&M Univ, Ctr Anim Biotechnol & Genom, College Stn, TX 77843 USA. [Lenis, Yasser Y.] Univ Antioquia, Sch Vet Med, Fac Agr Sci, Centauro Res Grp, Calle 70 52-21, Medellin, Colombia. [Wang, Xiaoqiu] NIEHS, Res Triangle Pk, NC 27709 USA. RP Bazer, FW (reprint author), Texas A&M Univ, Dept Anim Sci, College Stn, TX 77843 USA.; Bazer, FW (reprint author), Texas A&M Univ, Ctr Anim Biotechnol & Genom, College Stn, TX 77843 USA. EM fbazer@cvm.tamu.edu FU CODI University of Antioquia (UdeA); Medellin; Colombia Scholarship "Becas Doctorado UdeA; Agriculture and Food Research Initiative Competitive Grants from the USDA National Institute of Food and Agriculture [2011-67015-20028, 2015-67015-23276] FX This work was supported by Sustainability Strategy 2013-2014, from CODI University of Antioquia (UdeA), Medellin, Colombia Scholarship "Becas Doctorado UdeA 2014" (to YYL; PhD student in Veterinary Science, Faculty of Agrarian Science, Antioquia University) and by Agriculture and Food Research Initiative Competitive Grants (2011-67015-20028 and 2015-67015-23276) from the USDA National Institute of Food and Agriculture (to FWB and GW). Yasser Lenis is also a Research Fellow in the Department of Animal Science, Texas A&M University. NR 52 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0939-4451 EI 1438-2199 J9 AMINO ACIDS JI Amino Acids PD OCT PY 2016 VL 48 IS 10 BP 2389 EP 2399 DI 10.1007/s00726-016-2216-1 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DY8XC UT WOS:000385414500011 PM 27074718 ER PT J AU Charlifue, S Tate, D Biering-Sorensen, F Burns, S Chen, YY Chun, S Jakeman, LB Kowalski, RG Noonan, VK Ullrich, P AF Charlifue, Susan Tate, Denise Biering-Sorensen, Fin Burns, Stephen Chen, Yuying Chun, Sophia Jakeman, Lyn B. Kowalski, Robert G. Noonan, Vanessa K. Ullrich, Philip TI Harmonization of Databases: A Step for Advancing the Knowledge About Spinal Cord Injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Dataset; Database; Rehabilitation; Spinal cord injuries ID POPULATION HEALTH SURVEY; QUALITY-OF-LIFE; DEVELOPING-COUNTRIES; NEUROLOGICAL DISORDERS; NATIONAL INSTITUTE; DATA SET; CLASSIFICATION; EPIDEMIOLOGY; INDIVIDUALS; INSTRUMENTS AB The objectives of this article are to (1) provide an overview of existing spinal cord injury (SCI) clinical research databases-their purposes, characteristics, and accessibility to users; and (2) present a vision for future collaborations required for cross-cutting research in SCI. This vision highlights the need for validated and relevant data for longitudinal clinical trials and observational and epidemiologic SCI-related studies. Three existing SCI clinical research databases/registries are reviewed and summarized with regard to current formats, collection methods, and uses, including major strengths and weaknesses. Efforts to provide a uniform approach to data collection are also reviewed. The databases reviewed offer different approaches to capture important clinical information on SCI. They vary on size, purpose, data points, inclusion of standard outcomes, and technical requirements. Each presents with a set of limitations including lack of population data and lack of a common platform for data comparisons and exchanges. It is clear that numerous issues need to be considered when planning to establish common ways of collecting data through data sets or patient registries, ranging from a carefully crafted implementation plan that lists purposes, cost, resources required, and policies to guide such development to establishing a framework for dissemination of data and findings. For the present, taking advantage of the vast but different data already collected over many decades may require a variety of statistical skills and epidemiologic techniques. Ultimately, our ability to speak the same language with regard to variables and assessment tools will facilitate international collaborations and enhance comparability, data pooling, and the ability to generalize findings to a broader population. (C) 2016 by the American Congress of Rehabilitation Medicine C1 [Charlifue, Susan; Kowalski, Robert G.] Craig Hosp, Rocky Mt Reg Spinal Injury Syst, Englewood, CO USA. [Tate, Denise] Univ Michigan Spinal Cord Injury Model Syst, Dept Phys Med & Rehabil, Ann Arbor, MI USA. [Biering-Sorensen, Fin] Univ Copenhagen, Clin Spinal Cord Injuries, Rigshosp, Copenhagen, Denmark. [Burns, Stephen; Ullrich, Philip] Puget Sound Vet Adm Med Ctr, Vet Adm Spinal Cord Injury & Disorder Serv, Seattle, WA USA. [Burns, Stephen; Ullrich, Philip] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Chen, Yuying] Univ Alabama Birmingham, Dept Phys Med & Rehabil, Birmingham, AL USA. [Chun, Sophia] Vet Adm Long Beach Healthcare Syst, Spinal Cord Injury Ctr, Long Beach, CA USA. [Jakeman, Lyn B.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Noonan, Vanessa K.] Rick Hansen Inst, Vancouver, BC, Canada. RP Charlifue, S (reprint author), Craig Hosp, 3425 S Clarkson St, Englewood, CO 80110 USA. EM susie@craighospital.org FU National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) [90S15003, 90DP0011, 90SI5000]; Health Canada; Western Economic Diversification Canada; Government of Alberta; Government of British Columbia; Government of Manitoba; Government of Ontario FX Supported by the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR grant nos. 90S15003, 90DP0011, 90SI5000). NIDILRR is a Center within the Administration for Community Living (ACL), Department of Health and Human Services (HHS). The Rick Hansen Spinal Cord Injury Registry is supported by funding from Health Canada, Western Economic Diversification Canada, and the Governments of Alberta, British Columbia, Manitoba, and Ontario. The contents of this manuscript do not represent the opinions or policy of NIDILRR, ACL, National Institutes of Health, National Institute of Neurological Disorders and Stroke, or HHS, and do not imply endorsement by the respective institutes, agencies, or the U.S. Federal Government. NR 45 TC 1 Z9 1 U1 2 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 OCT PY 2016 VL 97 IS 10 BP 1805 EP 1818 DI 10.1016/j.apmr.2016.03.030 PG 14 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA DY7TX UT WOS:000385333300027 PM 27137095 ER PT J AU Hourigan, CS Aplan, PD AF Hourigan, Christopher S. Aplan, Peter D. TI Accurate Medicine: Indirect Targeting of NPM1-Mutated AML SO CANCER DISCOVERY LA English DT Editorial Material ID ACUTE MYELOID-LEUKEMIA; CLASSIFICATION; HOXA9 AB Acute myeloid leukemia (AML) is now recognized to be an imprecise term that refers to a range of myeloid malignancies that have different genetical etiologies, clinical characteristics, and therapeutic sensitivities. Targeting the MLL1 and DOT1L histone modification complexes, both alone and in combination, showed activity against AML driven by a mutant NPM1 protein in several preclinical models and may represent a new treatment direction for this devastating disease. (C) 2016 AACR. C1 [Hourigan, Christopher S.] NHLBI, Myeloid Malignancies Sect, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. [Aplan, Peter D.] NCI, Leukemia Biol Sect, Genet Branch, NIH, Bethesda, MD 20892 USA. RP Hourigan, CS; Aplan, PD (reprint author), NCI, NIH, 37 Convent Dr,Bldg 37 Room 6002, Bethesda, MD 20892 USA. EM christopher.hourigan@nih.gov; aplanp@mail.nih.gov RI Hourigan, Christopher/S-2476-2016 OI Hourigan, Christopher/0000-0002-6189-8067 FU Intramural Research Program of the NCI [ZIA SC 010378, ZIA BC 010982]; National Heart, Lung and Blood Institute of the NIH [ZIA HL 006163] FX This work was supported by the Intramural Research Program of the NCI (Grants ZIA SC 010378 and ZIA BC 010982 to P.D. Aplan) and the National Heart, Lung and Blood Institute of the NIH (Grant ZIA HL 006163 to C.S. Hourigan). NR 10 TC 0 Z9 0 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD OCT PY 2016 VL 6 IS 10 BP 1087 EP 1089 DI 10.1158/2159-8290.CD-16-0917 PG 3 WC Oncology SC Oncology GA DZ1ZW UT WOS:000385642200019 PM 27698101 ER PT J AU Trabert, B AF Trabert, Britton TI Body Powder and Ovarian Cancer Risk-What Is the Role of Recall Bias? SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; TALC USE; INFLAMMATION; MORTALITY; EXPOSURE C1 [Trabert, Britton] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Trabert, B (reprint author), NCI, 9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM britton.trabert@nih.gov RI Trabert, Britton/F-8051-2015 FU Intramural NIH HHS [ZIA CP010126-21] NR 17 TC 0 Z9 0 U1 4 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 OCT PY 2016 VL 25 IS 10 BP 1369 EP 1370 DI 10.1158/1055-9965.EPI-16-0476 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA DZ2AA UT WOS:000385642800001 PM 27697794 ER PT J AU Kennedy, AE Khoury, MJ Ioannidis, JPA Brotzman, M Miller, A Lane, C Lai, GY Rogers, SD Harvey, C Elena, JW Seminara, D AF Kennedy, Amy E. Khoury, Muin J. Ioannidis, John P. A. Brotzman, Michelle Miller, Amy Lane, Crystal Lai, Gabriel Y. Rogers, Scott D. Harvey, Chinonye Elena, Joanne W. Seminara, Daniela TI The Cancer Epidemiology Descriptive Cohort Database: A Tool to Support Population-Based Interdisciplinary Research SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOME-WIDE ASSOCIATION; PROSTATE-CANCER; PRECISION MEDICINE; PANCREATIC-CANCER; CLINICAL-TRIALS; PUBLIC-HEALTH; CONSORTIUM; RISK; TRANSFORMATION; BREAST AB Background: We report on the establishment of a web-based Cancer Epidemiology Descriptive Cohort Database (CEDCD). The CEDCD's goals are to enhance awareness of resources, facilitate interdisciplinary research collaborations, and support existing cohorts for the study of cancer-related outcomes. Methods: Comprehensive descriptive data were collected from large cohorts established to study cancer as primary outcome using a newly developed questionnaire. These included an inventory of baseline and follow-up data, biospecimens, genomics, policies, and protocols. Additional descriptive data extracted from publicly available sources were also collected. This information was entered in a searchable and publicly accessible database. We summarized the descriptive data across cohorts and reported the characteristics of this resource. Results: As of December 2015, the CEDCD includes data from 46 cohorts representing more than 6.5 million individuals (29% ethnic/racial minorities). Overall, 78% of the cohorts have collected blood at least once, 57% at multiple time points, and 46% collected tissue samples. Genotyping has been performed by 67% of the cohorts, while 46% have performed whole-genome or exome sequencing in subsets of enrolled individuals. Information on medical conditions other than cancer has been collected in more than 50% of the cohorts. More than 600,000 incident cancer cases and more than 40,000 prevalent cases are reported, with 24 cancer sites represented. Conclusions: The CEDCD assembles detailed descriptive information on a large number of cancer cohorts in a searchable database. Impact: Information from the CEDCD may assist the interdisciplinary research community by facilitating identification of well-established population resources and large-scale collaborative and integrative research. (C) 2016 AACR. C1 [Kennedy, Amy E.; Lai, Gabriel Y.; Rogers, Scott D.; Harvey, Chinonye; Elena, Joanne W.] NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, NIH, Rockville, MD USA. [Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA. [Ioannidis, John P. A.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Ioannidis, John P. A.] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [Ioannidis, John P. A.] Stanford Univ, Dept Stat, Stanford, CA 94305 USA. [Ioannidis, John P. A.] Stanford Univ, Meta Res Innovat Ctr Stanford METRICS, Stanford, CA 94305 USA. [Brotzman, Michelle; Miller, Amy] Westat Corp, Rockville, MD USA. [Lane, Crystal] US Hlth Resources & Serv Adm, Off Epidemiol & Res, Maternal & Child Hlth Bur, Rockville, MD 20857 USA. [Seminara, Daniela] NCI, Div Canc Control & Populat Sci, NIH, Rockville, MD USA. RP Seminara, D (reprint author), NCI, 9609 Med Ctr Dr,Room 3E336,MSC 9763, Bethesda, MD 20850 USA. EM seminard@mail.nih.gov OI Kennedy, Amy/0000-0001-9589-5510 NR 34 TC 0 Z9 0 U1 2 U2 2 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 OCT PY 2016 VL 25 IS 10 BP 1392 EP 1401 DI 10.1158/1055-9965.EPI-16-0412 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA DZ2AA UT WOS:000385642800004 PM 27439404 ER PT J AU Long, AH Highfill, SL Cui, YZ Smith, JP Walker, AJ Ramakrishna, S El-Etriby, R Galli, S Tsokos, MG Orentas, RJ Mackall, CL AF Long, Adrienne H. Highfill, Steven L. Cui, Yongzhi Smith, Jillian P. Walker, Alec J. Ramakrishna, Sneha El-Etriby, Rana Galli, Susana Tsokos, Maria G. Orentas, Rimas J. Mackall, Crystal L. TI Reduction of MDSCs with All-trans Retinoic Acid Improves CAR Therapy Efficacy for Sarcomas SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID MODIFIED T-CELLS; CHIMERIC ANTIGEN RECEPTORS; SUPPRESSOR-CELLS; MYELOID CELLS; IMMUNE-RESPONSE; CANCER; NEUROBLASTOMA; EXPANSION; CYTOKINE; ANTIBODY AB Genetically engineered T cells expressing CD19-specific chimeric antigen receptors (CAR) have shown impressive activity against B-cell malignancies, and preliminary results suggest that T cells expressing a first-generation disialoganglioside (GD2)-specific CAR can also provide clinical benefit in patients with neuroblastoma. We sought to assess the potential of GD2-CAR therapies to treat pediatric sarcomas. We observed that 18 of 18 (100%) of osteosarcomas, 2 of 15 (13%) of rhabdomyosarcomas, and 7 of 35 (20%) of Ewing sarcomas expressed GD2. T cells engineered to express a third-generation GD2-CAR incorporating the 14g2a-scFv with the CD28, OX40, and CD3 zeta signaling domains (14g2a.CD28.OX40.zeta) mediated efficient and comparable lysis of both GD2(+) sarcoma and neuroblastoma cell lines in vitro. However, in xenograft models, GD2-CAR T cells had no antitumor effect against GD2(+) sarcoma, despite effectively controlling GD2(+) neuroblastoma. We observed that pediatric sarcoma xenografts, but not neuroblastoma xenografts, induced large populations of monocytic and granulocytic murine myeloid-derived suppressor cells (MDSC) that inhibited human CAR T-cell responses in vitro. Treatment of sarcoma-bearing mice with all-trans retinoic acid (ATRA) largely eradicated monocytic MDSCs and diminished the suppressive capacity of granulocytic MDSCs. Combined therapy using GD2-CAR T cells plus ATRA significantly improved antitumor efficacy against sarcoma xenografts. We conclude that retinoids provide a clinically accessible class of agents capable of diminishing the suppressive effects of MDSCs, and that co-administration of retinoids may enhance the efficacy of CAR therapies targeting solid tumors. (C) 2016 AACR. C1 [Long, Adrienne H.; Highfill, Steven L.; Cui, Yongzhi; Smith, Jillian P.; Walker, Alec J.; Ramakrishna, Sneha; Orentas, Rimas J.; Mackall, Crystal L.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Long, Adrienne H.] Northwestern Univ, Feinberg Sch Med, Dept Microbiol & Immunol, Chicago, IL 60611 USA. [El-Etriby, Rana; Galli, Susana; Tsokos, Maria G.] NCI, Pathol Lab, CCR, NIH, Bldg 10, Bethesda, MD 20892 USA. [Mackall, Crystal L.] Stanford Univ, Sch Med, Dept Pediat, 265 Campus Dr G3141A, Stanford, CA 94305 USA. [Galli, Susana] Georgetown Univ, Med Ctr, Dept Biochem & Mol & Cellular Biol, Washington, DC 20007 USA. [Tsokos, Maria G.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Orentas, Rimas J.] Lentigen Technol Inc, Gaithersburg, MD USA. RP Mackall, CL (reprint author), Stanford Univ, 265 Campus Dr G3141A,MC5456, Stanford, CA 94305 USA. EM cmackall@stanford.edu FU Intramural NIH HHS [ZIA BC011073-03]; NIGMS NIH HHS [T32 GM008152] NR 50 TC 1 Z9 1 U1 6 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD OCT PY 2016 VL 4 IS 10 BP 869 EP 880 DI 10.1158/2326-6066.CIR-15-0230 PG 12 WC Oncology; Immunology SC Oncology; Immunology GA DZ1WR UT WOS:000385632900007 PM 27549124 ER PT J AU Cook, KL Soto-Pantoja, DR Clarke, PAG Cruz, MI Zwart, A Warri, A Hilakivi-Clarke, L Roberts, DD Clarke, R AF Cook, Katherine L. Soto-Pantoja, David R. Clarke, Pamela A. G. Cruz, M. Idalia Zwart, Alan Warri, Anni Hilakivi-Clarke, Leena Roberts, David D. Clarke, Robert TI Endoplasmic Reticulum Stress Protein GRP78 Modulates Lipid Metabolism to Control Drug Sensitivity and Antitumor Immunity in Breast Cancer SO CANCER RESEARCH LA English DT Article ID FATTY-ACID OXIDATION; ANTIESTROGEN RESPONSIVENESS; THERAPEUTIC TARGET; HEPATIC STEATOSIS; GENE-EXPRESSION; CELL FATE; RESISTANCE; TAMOXIFEN; AUTOPHAGY; CHOLESTEROL AB The unfolded protein response is an endoplasmic reticulum stress pathway mediated by the protein chaperone glucose regulated-protein 78 (GRP78). Metabolic analysis of breast cancer cells shows that GRP78 silencing increases the intracellular concentrations of essential polyunsaturated fats, including linoleic acid. Accumulation of fatty acids is due to an inhibition of mitochondrial fatty acid transport, resulting in a reduction of fatty acid oxidation. These data suggest a novel role of GRP78-mediating cellular metabolism. We validated the effect of GRP78-regulated metabolite changes by treating tumor-bearing mice with tamoxifen and/or linoleic acid. Tumors treated with linoleic acid plus tamoxifen exhibited reduced tumor area and tumor weight. Inhibition of either GRP78 or linoleic acid treatment increased MCP-1 serum levels, decreased CD47 expression, and increased macrophage infiltration, suggesting a novel role for GRP78 in regulating innate immunity. GRP78 control of fatty acid oxidation may represent a new homeostatic function for GRP78. (C) 2016 AACR. C1 [Cook, Katherine L.; Soto-Pantoja, David R.] Wake Forest Univ, Bowman Gray Sch Med, Dept Surg, Winston Salem, NC 27103 USA. [Cook, Katherine L.; Soto-Pantoja, David R.] Wake Forest Univ, Bowman Gray Sch Med, Hypertens & Vasc Res Ctr, Winston Salem, NC USA. [Cook, Katherine L.; Clarke, Pamela A. G.; Cruz, M. Idalia; Zwart, Alan; Warri, Anni; Hilakivi-Clarke, Leena; Clarke, Robert] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA. [Cook, Katherine L.; Clarke, Pamela A. G.; Cruz, M. Idalia; Zwart, Alan; Warri, Anni; Hilakivi-Clarke, Leena; Clarke, Robert] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [Roberts, David D.] NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Cook, KL (reprint author), Wake Forest Univ, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM klcook@wakehealth.edu RI Clarke, Robert/A-6485-2008; Roberts, David/A-9699-2008 OI Clarke, Robert/0000-0002-9278-0854; Roberts, David/0000-0002-2481-2981 FU NCATS NIH HHS [KL2 TR001421]; NCI NIH HHS [U54 CA149147, U01 CA184902, K22 CA181274, R01 CA131465] NR 45 TC 1 Z9 1 U1 7 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD OCT PY 2016 VL 76 IS 19 BP 5657 EP 5670 DI 10.1158/0008-5472.CAN-15-2616 PG 14 WC Oncology SC Oncology GA DZ1UD UT WOS:000385625500012 PM 27698188 ER PT J AU He, XZ Yan, B Liu, S Jia, JT Lai, WW Xin, X Tang, CE Luo, DX Tan, T Jiang, YQ Shi, Y Liu, YT Xiao, DS Chen, L Liu, S Mao, C Yin, G Cheng, Y Fan, J Cao, Y Muegge, K Tao, YG AF He, Xiaozhen Yan, Bin Liu, Shuang Jia, Jiantao Lai, Weiwei Xin, Xing Tang, Can-e Luo, Dixian Tan, Tan Jiang, Yiqun Shi, Ying Liu, Yating Xiao, Desheng Chen, Ling Liu, Shao Mao, Chao Yin, Gang Cheng, Yan Fan, Jia Cao, Ya Muegge, Kathrin Tao, Yongguang TI Chromatin Remodeling Factor LSH Drives Cancer Progression by Suppressing the Activity of Fumarate Hydratase SO CANCER RESEARCH LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; NF-KAPPA-B; DNA METHYLATION; GENE-EXPRESSION; NASOPHARYNGEAL CARCINOMA; STEM-CELLS; IKK-ALPHA; EPIGENETICS; METABOLISM; PHOSPHORYLATION AB Chromatin modification is pivotal to the epithelial-mesenchymal transition (EMT), which confers potent metastatic potential to cancer cells. Here, we report a role for the chromatin remodeling factor lymphoid-specific helicase (LSH) in nasopharyngeal carcinoma (NPC), a prevalent cancer in China. LSH expression was increased in NPC, where it was controlled by the Epstein-Barr virus-encoded protein LMP1. In NPC cells in vitro and in vivo, LSH promoted cancer progression in part by regulating expression of fumarate hydratase (FH), a core component of the tricarboxylic acid cycle. LSH bound to the FH promoter, recruiting the epigenetic silencer factor G9a to repress FH transcription. Clinically, we found that the concentration of TCA intermediates in NPC-patient sera was deregulated in the presence of LSH. RNAi-mediated silencing of FH mimicked LSH overexpression, establishing FH as downstream mediator of LSH effects. The TCA intermediates a-KG and citrate potentiated the malignant character of NPC cells, in part by altering IKK alpha-dependent EMT gene expression. In this manner, LSH furthered malignant progression of NPC by modifying cancer cell metabolism to support EMT. (C) 2016 AACR. C1 [He, Xiaozhen; Yan, Bin; Liu, Shuang; Jia, Jiantao; Lai, Weiwei; Xin, Xing; Tang, Can-e; Jiang, Yiqun; Shi, Ying; Liu, Yating; Chen, Ling; Mao, Chao; Cao, Ya; Tao, Yongguang] Cent S Univ, Xiangya Hosp, Ctr Med Res, Changsha, Hunan, Peoples R China. [He, Xiaozhen; Yan, Bin; Jia, Jiantao; Lai, Weiwei; Xin, Xing; Jiang, Yiqun; Shi, Ying; Liu, Yating; Chen, Ling; Mao, Chao; Cao, Ya; Tao, Yongguang] Cent S Univ, Sch Basic Med, Canc Res Inst, Changsha, Hunan, Peoples R China. [He, Xiaozhen; Yan, Bin; Jia, Jiantao; Lai, Weiwei; Xin, Xing; Jiang, Yiqun; Shi, Ying; Liu, Yating; Chen, Ling; Mao, Chao; Cao, Ya; Tao, Yongguang] Cent S Univ, Minist Educ, Key Lab Carcinogenesis & Canc Invas, Changsha, Hunan, Peoples R China. [He, Xiaozhen; Yan, Bin; Xin, Xing; Shi, Ying; Liu, Yating; Chen, Ling; Cao, Ya; Tao, Yongguang] Cent S Univ, Minist Hlth, Key Lab Carcinogenesis, Changsha, Hunan, Peoples R China. [Luo, Dixian; Tan, Tan] Univ South China, Peoples Hosp Chenzhou 1, Natl & Local Joint Engn Lab High Throughput Mol D, Translat Med Inst, Chenzhou, Hunan, Peoples R China. [Xiao, Desheng] Cent S Univ, Xiangya Hosp, Dept Pathol, Changsha, Hunan, Peoples R China. [Liu, Shao] Cent S Univ, Xiangya Hosp, Dept Pharm, Changsha, Hunan, Peoples R China. [Yin, Gang] Cent S Univ, Sch Basic Med, Dept Pathol, Changsha, Hunan, Peoples R China. [Cheng, Yan] Cent S Univ, Sch Pharmaceut Sci, Dept Pharmacol, Changsha, Hunan, Peoples R China. [Fan, Jia] Fudan Univ, Key Lab Carcinogenesis & Canc Invas, Liver Canc Inst, Liver Surg Dept,Zhongshan Hosp,Minist Educ, Shanghai, Peoples R China. [Fan, Jia] Fudan Univ, Inst Biomed Sci, Shanghai, Peoples R China. [Muegge, Kathrin] NCI, Mouse Canc Genet Program, Basic Sci Program, Leidos Biomed Res Inc,Frederick Natl Lab Canc Res, Frederick, MD 21701 USA. RP Tao, YG (reprint author), Cent S Univ, Xiangya Hosp, 110 Xiangya Rd, Changsha 410078, Hunan, Peoples R China. EM taoyong@csu.edu.cn RI Shi, Ying-Hong/B-7063-2017 NR 56 TC 1 Z9 1 U1 5 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD OCT PY 2016 VL 76 IS 19 BP 5743 EP 5755 DI 10.1158/0008-5472.CAN-16-0268 PG 13 WC Oncology SC Oncology GA DZ1UD UT WOS:000385625500019 PM 27302170 ER PT J AU Patel, YM Park, SL Han, YH Wilkens, LR Bickeboller, H Rosenberger, A Caporaso, N Landi, MT Bruske, I Risch, A Wei, YY Christiani, DC Brennan, P Houlston, R McKay, J McLaughlin, J Hung, R Murphy, S Stram, DO Amos, C Le Marchand, L AF Patel, Yesha M. Park, Sunghim L. Han, Younghun Wilkens, Lynne R. Bickeboeller, Heike Rosenberger, Albert Caporaso, Neil Landi, Maria Teresa Brueske, Irene Risch, Angela Wei, Yongyue Christiani, David C. Brennan, Paul Houlston, Richard McKay, James McLaughlin, John Hung, Rayjean Murphy, Sharon Stram, Daniel O. Amos, Christopher Le Marchand, Loic TI Novel Association of Genetic Markers Affecting CYP2A6 Activity and Lung Cancer Risk SO CANCER RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; NICOTINE METABOLISM; SUSCEPTIBILITY LOCUS; ETHNIC/RACIAL GROUPS; SMOKING-BEHAVIOR; COMPLEX TRAITS; METAANALYSIS; VARIANTS; GENOTYPE; GLUCURONIDATION AB Metabolism of nicotine by cytochrome P450 2A6 (CYP2A6) is a suspected determinant of smoking dose and, consequently, lung cancer risk. We conducted a genome-wide association study (GWAS) of CYP2A6 activity, as measured by the urinary ratio of trans-3'-hydroxycotinine and its glucuronide conjugate over cotinine (total 3HCOT/COT), among 2,239 smokers in the Multiethnic Cohort (MEC) study. We identified 248 CYP2A6 variants associated with CYP2A6 activity (P < 5 x 10(-8)). CYP2A6 activity was correlated (r = 0.32; P < 0.0001) with total nicotine equivalents (a measure of nicotine uptake). When we examined the effect of these variants on lung cancer risk in the Transdisciplinary Research in Cancer of the Lung (TRICL) consortium GWAS dataset (13,479 cases and 43,218 controls), we found that the vast majority of these individual effects were directionally consistent and associated with an increased lung cancer risk. Two hundred and twenty-six of the 248 variants associated with CYP2A6 activity in the MEC were available in TRICL. Of them, 81% had directionally consistent risk estimates, and six were globally significantly associated with lung cancer. When conditioning on nine known functional variants and two deletions, the top two SNPs (rs56113850 in MEC and rs35755165 in TRICL) remained significantly associated with CYP2A6 activity in MEC and lung cancer in TRICL. The present data support the hypothesis that a greater CYP2A6 activity causes smokers to smoke more extensively and be exposed to higher levels of carcinogens, resulting in an increased risk for lung cancer. Although the variants identified in these studies may be used as risk prediction markers, the exact causal variants remain to be identified. (C) 2016 AACR. C1 [Patel, Yesha M.; Park, Sunghim L.; Stram, Daniel O.] Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. [Patel, Yesha M.; Park, Sunghim L.; Stram, Daniel O.] Univ Southern Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA USA. [Han, Younghun; Amos, Christopher] Dartmouth Coll, Dept Biomed Data Sci, Hanover, NH 03755 USA. [Wilkens, Lynne R.; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA. [Bickeboeller, Heike; Rosenberger, Albert] Univ Gottingen, Univ Med Ctr, Dept Genet Epidemiol, Gottingen, Germany. [Caporaso, Neil; Landi, Maria Teresa] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Brueske, Irene] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Epidemiol 1, Neuherberg, Germany. [Risch, Angela] Salzburg Univ, Dept Mol Biol, Salzburg, Austria. [Wei, Yongyue] Nanjing Med Univ, Sch Publ Hlth, Nanjing, Jiangsu, Peoples R China. [Christiani, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Christiani, David C.] Harvard Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Brennan, Paul; McKay, James] Int Agcy Res Canc, Genet Epidemiol Grp, Lyon, France. [Houlston, Richard] Inst Canc Res, Div Genet & Epidemiol, London, England. [McLaughlin, John] Publ Hlth Ontario, Toronto, ON, Canada. [Hung, Rayjean] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada. [Murphy, Sharon] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN USA. [Murphy, Sharon] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. RP Le Marchand, L (reprint author), Univ Hawaii, Ctr Canc, 701 Ilalo St,Room 530, Honolulu, HI 96813 USA. EM loic@cc.hawaii.edu RI Risch, Angela/H-2669-2013 OI Risch, Angela/0000-0002-8026-5505 FU CCR NIH HHS [N01RC37004]; NCI NIH HHS [K07 CA160753, N01 CN045165, N01 CN25404, N01 CN25476, N01 CN25511, N01 CN25512, N01 CN25513, N01 CN25514, N01 CN25515, N01 CN25516, N01 CN25518, N01 CN25522, N01 CN25524, N01 CN75022, P01 CA138338, P20 CA090578, P30 CA023108, P50 CA070907, P50 CA090578, R01 CA055769, R01 CA074386, R01 CA092039, R01 CA092824, R01 CA111703, R01 CA121197, R01 CA127219, R01 CA133996, U01 CA063673, U01 CA164973, U19 CA148127, UM1 CA167462]; NHGRI NIH HHS [HHSN268200782096C, U01 HG004438, U01 HG004446] NR 50 TC 2 Z9 2 U1 5 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD OCT PY 2016 VL 76 IS 19 BP 5768 EP 5776 DI 10.1158/0008-5472.CAN-16-0446 PG 9 WC Oncology SC Oncology GA DZ1UD UT WOS:000385625500021 PM 27488534 ER PT J AU Murphy, B Yin, H Maris, JM Kolb, EA Gorlick, R Reynolds, CP Kang, MH Keir, ST Kurmasheva, RT Dvorchik, I Wu, JR Billups, CA Boateng, N Smith, MA Lock, RB Houghton, PJ AF Murphy, Brendan Yin, Han Maris, John M. Kolb, E. Anders Gorlick, Richard Reynolds, C. Patrick Kang, Min H. Keir, Stephen T. Kurmasheva, Raushan T. Dvorchik, Igor Wu, Jianrong Billups, Catherine A. Boateng, Nana Smith, Malcolm A. Lock, Richard B. Houghton, Peter J. TI Evaluation of Alternative In Vivo Drug Screening Methodology: A Single Mouse Analysis SO CANCER RESEARCH LA English DT Article ID PRECLINICAL TESTING PROGRAM; ACUTE LYMPHOBLASTIC-LEUKEMIA; HUMAN COLORECTAL TUMORS; IMMUNE-DEPRIVED MICE; CELL LUNG-CANCER; MONOCLONAL-ANTIBODY; XENOGRAFT MODELS; STAGE 1; BMN 673; RHABDOMYOSARCOMA AB Traditional approaches to evaluating antitumor agents using human tumor xenograft models have generally used cohorts of 8 to 10 mice against a limited panel of tumor models. An alternative approach is to use fewer animals per tumor line, allowing a greater number of models that capture greater molecular/genetic heterogeneity of the cancer type. We retrospectively analyzed 67 agents evaluated by the Pediatric Preclinical Testing Program to determine whether a single mouse, chosen randomly from each group of a study, predicted the median response for groups of mice using 83 xenograft models. The individual tumor response from a randomly chosen mouse was compared with the group median response using established response criteria. A total of 2,134 comparisons were made. The single tumor response accurately predicted the group median response in 1,604 comparisons (75.16%). The mean tumor response correct prediction rate for 1,000 single mouse random samples was 78.09%. Models had a range for correct prediction (60%-87.5%). Allowing for misprediction of +/- one response category, the overall mean correct single mouse prediction rate was 95.28%, and predicted overall objective response rates for group data in 66 of 67 drug studies. For molecularly targeted agents, occasional exceptional responder models were identified and the activity of that agent confirmed in additional models with the same genotype. Assuming that large treatment effects are targeted, this alternate experimental design has similar predictive value as traditional approaches, allowing for far greater numbers of models to be used that more fully encompass the heterogeneity of disease types. (C) 2016 AACR. C1 [Murphy, Brendan; Yin, Han; Houghton, Peter J.] Nationwide Childrens Hosp, Res Inst, Ctr Childhood Canc & Blood Dis, Columbus, OH USA. [Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Maris, John M.] Abramson Family Canc Res Inst, Philadelphia, PA USA. [Kolb, E. Anders] Alfred I DuPont Hosp Children, Dept Pediat, Wilmington, DE USA. [Gorlick, Richard] Childrens Hosp Montefiore, Dept Pediat, Bronx, NY USA. [Reynolds, C. Patrick] Texas Tech Univ, Hlth Sci Ctr, Dept Internal Med & Pediat, Lubbock, TX 79430 USA. [Kang, Min H.] Texas Tech Univ, Hlth Sci Ctr, Dept Cell Biol & Biochem, Lubbock, TX 79430 USA. [Keir, Stephen T.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Kurmasheva, Raushan T.; Houghton, Peter J.] Univ Texas Hlth Sci Ctr San Antonio, Greehey Childrens Canc Res Inst, Dept Mol Med, San Antonio, TX 78229 USA. [Dvorchik, Igor] Nationwide Childrens Hosp, Res Inst, Biostat, Columbus, OH USA. [Wu, Jianrong; Billups, Catherine A.; Boateng, Nana] St Jude Childrens Res Hosp, Dept Biostat, 332 N Lauderdale St, Memphis, TN 38105 USA. [Smith, Malcolm A.] NCI, Clin Invest Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Lock, Richard B.] Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia. RP Houghton, PJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, 8403 Floyd Curl Dr,Mail Code 7794, San Antonio, TX 78229 USA. EM houghtonp@uthscsa.edu RI Lock, Richard/G-4253-2013 FU NCI NIH HHS [N01 CM042216, N01CM42216, P01 CA165995, U01 CA199297] NR 48 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD OCT PY 2016 VL 76 IS 19 BP 5798 EP 5809 DI 10.1158/0008-5472.CAN-16-0122 PG 12 WC Oncology SC Oncology GA DZ1UD UT WOS:000385625500024 PM 27496711 ER PT J AU Xu, R Shimizu, F Hoyinga, K Beal, K Karimi, S Droms, L Peck, KK Gutin, P Iorgulescu, JB Kaley, T DeAngelis, L Pentsova, E Nolan, C Grommes, C Chan, T Bobrow, D Hormigo, A Cross, JR Wu, N Takebe, N Panageas, K Ivy, P Supko, JG Tabar, V Omuro, A AF Xu, Ran Shimizu, Fumiko Hoyinga, Koos Beal, Kathryn Karimi, Sasan Droms, Leif Peck, Kyung K. Gutin, Philip Iorgulescu, J. Bryan Kaley, Thomas DeAngelis, Lisa Pentsova, Elena Nolan, Craig Grommes, Christian Chan, Timothy Bobrow, Dylan Hormigo, Adilia Cross, Justin R. Wu, Nian Takebe, Naoko Panageas, Katherine Ivy, Percy Supko, Jeffrey G. Tabar, Viviane Omuro, Antonio TI Molecular and Clinical Effects of Notch Inhibition in Glioma Patients: A Phase O/I Trial SO CLINICAL CANCER RESEARCH LA English DT Article ID GAMMA-SECRETASE INHIBITOR; ADVANCED SOLID TUMORS; NEWLY-DIAGNOSED GLIOBLASTOMA; CANCER STEM-CELLS; SIGNALING PATHWAY; INITIATING CELLS; RO4929097; ANGIOGENESIS; COMBINATION; GROWTH AB Purpose: High-grade gliomas are associated with a dismal prognosis. Notch inhibition via the gamma-secretase inhibitor RO4929097 has emerged as a potential therapeutic option based on modulation of the cancer-initiating cell (CIS) population and a presumed antiangiogenic role. Experimental Design: In this phase O/I trial, 21 patients with newly diagnosed glioblastoma or anaplastic as trocytoma received RO4929097 combined with temozolomide and radiotherapy. In addition to establishing the MTD, the study design enabled exploratory studies evaluating tumor and brain drug penetration and neuroimaging parameters. We also determined functional effects on the Notch pathway and targeting of CISs through analysis of tumor tissue sampled from areas with and without blood-brain barrier disruption. Finally, recurrent tumors were also sampled and assessed for Notch pathway responses while on treatment. Results: Treatment was well tolerated and no dose-limiting toxicities were observed. 1FIC of treated tumors showed a significant decrease in proliferation and in the expression of the Notch intracellular domain (NICD) by tumor cells and blood vessels. Patient-specific organotypic tumor explants cultures revealed a specific decrease in the CD133(+) CIS population upon treatment. Perfusion MRI demonstrated a significant decrease in relative plasma volume after drug exposure. Gene expression data in recurrent tumors suggested low Notch signaling activity, the upregulation of key mesenchymal genes, and an increase in VEGF-dependent angiogenic factors. Conclusions: The addition of RO4929097 to temozolomide and radiotherapy was well tolerated; the drug has a variable blood-brain barrier penetration. Evidence of target modulation was observed, but recurrence occurred, associated with alterations in angiogenesis signaling pathways. (C) 2016 AACR. C1 [Xu, Ran; Shimizu, Fumiko; Hoyinga, Koos; Droms, Leif; Gutin, Philip; Iorgulescu, J. Bryan; Tabar, Viviane] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, 1275 York Ave, New York, NY 10065 USA. [Xu, Ran; Shimizu, Fumiko; Hoyinga, Koos; Droms, Leif; Gutin, Philip; Iorgulescu, J. Bryan; Tabar, Viviane] Mem Sloan Kettering Canc Ctr, Ctr Stem Cell Biol, 1275 York Ave, New York, NY 10021 USA. [Xu, Ran] Charite, Dept Neurosurg, Berlin, Germany. [Beal, Kathryn; Chan, Timothy] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, 1275 York Ave, New York, NY 10021 USA. [Karimi, Sasan; Peck, Kyung K.] Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave, New York, NY 10021 USA. [Kaley, Thomas; DeAngelis, Lisa; Pentsova, Elena; Nolan, Craig; Grommes, Christian; Bobrow, Dylan; Hormigo, Adilia; Omuro, Antonio] Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10021 USA. [Hormigo, Adilia] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA. [Hormigo, Adilia] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Hormigo, Adilia] Icahn Sch Med Mt Sinai, Dept Neurosurg, New York, NY 10029 USA. [Hormigo, Adilia] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. [Cross, Justin R.] Mem Sloan Kettering Canc Ctr, Donald B & Catherine C Marron Canc Metab Ctr, 1275 York Ave, New York, NY 10021 USA. [Wu, Nian] Mem Sloan Kettering Canc Ctr, Analyt Pharmacol Core, 1275 York Ave, New York, NY 10021 USA. [Wu, Nian] LipoSeuticals Inc, Princeton, NJ USA. [Takebe, Naoko] NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Panageas, Katherine] Mem Sloan Kettering Canc Ctr, Epidemiol & Stat, 1275 York Ave, New York, NY 10021 USA. [Ivy, Percy] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Supko, Jeffrey G.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Iorgulescu, J. Bryan] Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. RP Tabar, V (reprint author), Mem Sloan Kettering Canc Ctr, Dept Neurosurg, 1275 York Ave, New York, NY 10065 USA. EM tabarv@mskcc.org FU NIH/NCI (NCI Cancer Clinical Investigator Team Leadership Award) [3P30CA008748-47S2, U01CA069856]; B*Cured Foundation; Philadelphia Foundation; Have a Chance Foundation FX The study was partially funded by NIH/NCI through grants 3P30CA008748-47S2 (NCI Cancer Clinical Investigator Team Leadership Award; to A.M.P. Omuro) and U01CA069856. Additional funding was provided by B*Cured Foundation, Philadelphia Foundation, and Have a Chance Foundation. NR 36 TC 5 Z9 6 U1 4 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2016 VL 22 IS 19 BP 4786 EP 4796 DI 10.1158/1078-0432.CCR-16-0048 PG 11 WC Oncology SC Oncology GA DZ1VV UT WOS:000385630500006 PM 27154916 ER PT J AU Muller, F Cunningham, T Liu, XF Wayne, AS Pastan, I AF Mueller, Fabian Cunningham, Tyler Liu, Xiu Fen Wayne, Alan S. Pastan, Ira TI Wide Variability in the Time Required for Immunotoxins to Kill B Lineage Acute Lymphoblastic Leukemia Cells: Implications for Trial Design SO CLINICAL CANCER RESEARCH LA English DT Article ID PHASE-II TRIAL; RECOMBINANT IMMUNOTOXIN; ANTI-CD22 IMMUNOTOXIN; RFB4(DSFV)-PE38 BL22; MOXETUMOMAB PASUDOTOX; IN-VITRO; THERAPY; BLINATUMOMAB; MALIGNANCIES; CONJUGATE AB Purpose: Recombinant immunotoxins (rITs) targeting CD22 are highly active in hairy cell leukemia, but less so in acute lymphoblastic leukemia (ALL). This study aims to understand the variable activity of an rIT against ALL toward improving responses in clinical application. Experimental Design: We determined in vitro activity of rITs by WST-8 assays and the time needed to kill ALL cell lines and patient-derived ALL blasts by flow cytometry. The findings were translated into two systemic ALL xenograft models. Differences in time needed to kill KOPN-8 cells for distinct rITs were addressed biochemically. Results: In vitro activity (IC50) of anti-CD22 rIT varied 210-fold from 0.02 to 4.6 ng/mL. Activity also varied greatly depending on the time ALL cells were exposed to immunotoxin from < 30 minutes to > 4 days. For KOPN-8, the difference in exposure time was related to intracellular rIT processing. We showed in newly developed ALL xenograft models, where immunotoxins have a short half-life, that the needed exposure time in vitro predicted the responses in vivo. By replacing bolus dose with small doses at frequent intervals or with continuous infusion, responses were substantially improved. We confirmed exposure time variability on patient-derived ALL samples and showed a correlation between exposure time needed to reach maximal cytotoxicity in vitro and their clinical response. Conclusions: The exposure time needed for rITs targeting CD22 to kill ALL cells varies widely. Our results suggest that ALL patients would have a better response rate to anti-CD22 immunotoxins if treated by continuous infusion rather than by bolus injections. (C) 2016 AACR. C1 [Mueller, Fabian; Cunningham, Tyler; Liu, Xiu Fen; Pastan, Ira] NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. [Wayne, Alan S.] Univ Southern Calif, Keck Sch Med, Norris Comprehens Canc Ctr,Childrens Ctr Canc & B, Childrens Hosp Los Angeles,Div Hematol Oncol & Bl, Los Angeles, CA USA. RP Pastan, I (reprint author), NCI, NIH, 37 Convent Dr,Rm 5106, Bethesda, MD 20892 USA. EM pastani@mail.nih.gov FU NCI [P30CA014089]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; Medimmune, LLC; German Research Foundation [MU 3619/1 1]; Cooperative Research and Development Agreement FX The work was supported in part by award number P30CA014089 from the NCI, the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and with a Cooperative Research and Development Agreement (#1975) with Medimmune, LLC. F. Muller was supported in part by the German Research Foundation (award number MU 3619/1 1). NR 42 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2016 VL 22 IS 19 BP 4913 EP 4922 DI 10.1158/1078-0432.CCR-15-2500 PG 10 WC Oncology SC Oncology GA DZ1VV UT WOS:000385630500018 PM 27114443 ER PT J AU Lozier, JN Kloos, MT Merricks, EP Lemoine, N Whitford, MH Raymer, RA Bellinger, DA Nichols, TC AF Lozier, Jay N. Kloos, Mark T. Merricks, Elizabeth P. Lemoine, Nathaly Whitford, Margaret H. Raymer, Robin A. Bellinger, Dwight A. Nichols, Timothy C. TI Severe Hemophilia A in a Male Old English Sheep Dog with a C -> T Transition that Created a Premature Stop Codon in Factor VIII SO COMPARATIVE MEDICINE LA English DT Article ID DEFICIENT MOUSE MODEL; MOLECULAR CHARACTERIZATION; INHIBITOR DEVELOPMENT; BLEEDING DISORDERS; ANIMAL-MODELS; GENE; MUTATION; SPECTRUM; DISEASE; IDENTIFICATION AB Animals with hemophilia are models for gene therapy, factor replacement, and inhibitor development in humans. We have actively sought dogs with severe hemophilia A that have novel factor VIII mutations unlike the previously described factor VIII intron 22 inversion. A male Old English Sheepdog with recurrent soft-tissue hemorrhage and hemarthrosis was diagnosed with severe hemophilia A (factor VIII activity less than 1% of normal). We purified genomic DNA from this dog and ruled out the common intron 22 inversion; we then sequenced all 26 exons. Comparing the results with the normal canine factor VIII sequence revealed a C -> T transition in exon 12 of the factor VIII gene that created a premature stop codon at amino acid 577 in the A2 domain of the protein. In addition, 2 previously described polymorphisms that do not cause hemophilia were present at amino acids 909 and 1184. The hemophilia mutation creates a new TaqI site that facilitates rapid genotyping of affected offspring by PCR and restriction endonuclease analyses. This mutation is analogous to the previously described human factor VIII mutation at Arg583, which likewise is a CpG dinucleotide transition causing a premature stop codon in exon 12. Thus far, despite extensive treatment with factor VIII, this dog has not developed neutralizing antibodies ('inhibitors') to the protein. This novel mutation in a dog gives rise to severe hemophilia A analogous to a mutation seen in humans. This model will be useful for studies of the treatment of hemophilia. C1 [Lozier, Jay N.] NIH, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Kloos, Mark T.; Merricks, Elizabeth P.; Lemoine, Nathaly; Whitford, Margaret H.; Raymer, Robin A.; Bellinger, Dwight A.; Nichols, Timothy C.] Univ North Carolina Chapel Hill, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. RP Nichols, TC (reprint author), Univ North Carolina Chapel Hill, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. EM tnichols@med.unc.edu FU NIH Intramural Research Program; NHLBI [HL63098] FX Funded by the NIH Intramural Research Program and NHLBI grant no. HL63098. NR 50 TC 0 Z9 0 U1 2 U2 2 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 OCT PY 2016 VL 66 IS 5 BP 405 EP 411 PG 7 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA DZ1OP UT WOS:000385608000007 PM 27780008 ER PT J AU Cadena, AM Klein, EC White, AG Tomko, JA Chedrick, CL Reed, DS Via, LE Lin, PL Flynn, JL AF Cadena, Anthony M. Klein, Edwin C. White, Alexander G. Tomko, Jaime A. Chedrick, Chelsea L. Reed, Douglas S. Via, Laura E. Lin, Philana Ling Flynn, JoAnne L. TI Very Low Doses of Mycobacterium tuberculosis Yield Diverse Host Outcomes in Common Marmosets (Callithrix jacchus) SO COMPARATIVE MEDICINE LA English DT Article ID CYNOMOLGUS MACAQUES; BIOMEDICAL-RESEARCH; INFECTION; MODEL; VIRULENCE; DISEASE AB Identifying and refining small-animal models of tuberculosis that recapitulate aspects of human Mycobacterium tuberculosis infection can contribute to advancing our understanding of critical facets of the disease. To study the effects of very low-dose infections with 2 strains of M. tuberculosis on disease progression and survival in common marmosets, animals were challenged with strains Erdman and CDC1551 at doses ranging from 1 to 12 cfu. These data revealed that the susceptibility of marmosets to M. tuberculosis infection is influenced by strain virulence and initial dose. Marmoset infection with the Erdman strain, even at very low doses, resulted in rapid disease progression associated with severe weight loss, extensive pathology, and poor survival. By contrast, challenge with the less virulent CDC1551 strain resulted in slower disease progression, delayed weight loss, and prolonged survival. One marmoset infected with CDC1551 at a very low dose (approximately 1 cfu) was able to contain and control M. tuberculosis infection in a subclinical state that persisted as long as 300 d. These findings underscore the critical importance of understanding the heterogeneity in host outcome that can arise in association with different infectious doses and strains in the marmoset model of tuberculosis. C1 [Cadena, Anthony M.; White, Alexander G.; Tomko, Jaime A.; Chedrick, Chelsea L.; Flynn, JoAnne L.] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15260 USA. [Klein, Edwin C.] Univ Pittsburgh, Sch Med, Dept Immunol, Ctr Vaccine Res, Pittsburgh, PA USA. [Reed, Douglas S.] Univ Pittsburgh, Div Lab Anim Res, Pittsburgh, PA USA. [Via, Laura E.] NIAID, TB Res Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Via, Laura E.] Univ Cape Town, Dept Pathol, Inst Infect Dis & Mol Med, Cape Town, South Africa. [Lin, Philana Ling] Univ Pittsburgh, Childrens Hosp Pittsburgh UPMC, Sch Med, Div Infect Dis,Dept Pediat, Pittsburgh, PA USA. RP Flynn, JL (reprint author), Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15260 USA. EM joanne@pitt.edu FU NIH training grant [T32 AI089443]; Bill and Melinda Gates Foundation [OPP1034408]; intramural research program of NIAID, NIH FX We thank Mark Rodgers, Carolyn Bigbee, Catherine Cochran, and Charles Scanga for technical assistance. We also thank Daniel Filmore for veterinary and animal assistance. We gratefully acknowledge Pauline Maiello and Teresa Coleman for imaging support and Danielle Weiner, Daniel Schimel, and Manny Dayao for veterinary assistance at NIAID. These studies were funded in part by a NIH training grant (T32 AI089443 [to AMC]), the Bill and Melinda Gates Foundation (grant no. OPP1034408 [to JLF]), and the intramural research program of NIAID, NIH (to LEV). NR 23 TC 0 Z9 0 U1 2 U2 2 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 OCT PY 2016 VL 66 IS 5 BP 412 EP 419 PG 8 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA DZ1OP UT WOS:000385608000008 PM 27780009 ER PT J AU Wang, XW Wang, HR Guo, B Zhang, Y Gong, Y Zhang, C Xu, H Wu, XH AF Wang, Xiaowen Wang, Herui Guo, Bin Zhang, Ya Gong, Yinv Zhang, Chi Xu, Hong Wu, Xiaohui TI Gen1 and Eme1 Play Redundant Roles in DNA Repair and Meiotic Recombination in Mice SO DNA AND CELL BIOLOGY LA English DT Article DE Gen1; Eme1; DNA repair; meiotic recombination ID HOLLIDAY JUNCTION RESOLVASE; STRUCTURE-SPECIFIC NUCLEASES; MAMMALIAN-CELLS; RESOLUTION; MUS81-EME1; SLX1-SLX4; YEN1; PATHWAYS; MEIOSIS; YEAST AB Resolution of the Holliday junction (HJ) is essential for homologous recombination and DNA repair. In Saccharomyces cerevisiae, HJ resolvase Yen1 and the Mus81-Mms4 complex are redundant in DNA damage repair. In cultured mammalian cells, such redundancy also exists between Yen1 ortholog GEN1 and the Mus81-Mms1 ortholog MUS81-EME1. In this report, we further tested if GEN1 and EME1 redundantly affect HJ-related physiological processes in mice. We found that combined homozygous mutations of Gen1 and Eme1 led to synthetic lethality during early embryonic stages. Homozygous Gen1 mutations did not cause DNA repair deficiency in mouse embryonic fibroblast (MEF) cells, but made heterozygous Eme1 mutant MEFs more sensitive to various DNA-damaging reagents. Gen1 mutations also reduced the meiotic recombination efficiency in Eme1 mutant mice. These results suggest that Gen1 and Eme1 play redundant roles in DNA repair and meiotic recombination in vivo. C1 [Wang, Xiaowen; Zhang, Ya; Gong, Yinv; Xu, Hong; Wu, Xiaohui] Fudan Univ, Childrens Hosp, Shanghai Kidney Dev & Pediat Kidney Dis Res Ctr, Shanghai, Peoples R China. [Wang, Xiaowen] Wuhan Med & Healthcare Ctr Women & Children, Dept Nephrol, Wuhan, Peoples R China. [Wang, Herui; Guo, Bin; Zhang, Chi; Wu, Xiaohui] Fudan Univ, Collaborat Innovat Ctr Genet & Dev, Inst Dev Biol & Mol Med, State Key Lab Genet Engn,Sch Life Sci, Shanghai, Peoples R China. [Wang, Herui; Guo, Bin; Zhang, Chi; Wu, Xiaohui] Fudan Univ, Collaborat Innovat Ctr Genet & Dev, Inst Dev Biol & Mol Med, Natl Ctr Int Res Dev & Dis,Sch Life Sci, Shanghai, Peoples R China. [Wang, Herui] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD USA. [Zhang, Chi] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA. RP Wu, XH (reprint author), Fudan Univ, Inst Dev Biol & Mol Med, Shanghai 200433, Peoples R China.; Xu, H (reprint author), Fudan Univ, Childrens Hosp, Dept Nephrol & Rheumatol, Shanghai 201102, Peoples R China. EM hxu@shmu.edu.cn; xiaohui_wu@fudan.edu.cn FU National Natural Science Foundation of China [81270763]; Chinese Hi-Tech Research and Development Project [2014AA021104]; Chinese Key Projects for Basic Research [2011CB944001]; Shanghai Municipal Government [15XD1500500, 12431900100]; State Key Laboratory of Genetic Engineering, Fudan University FX The authors thank Dr. Kai Lei, Zhisheng Ye, and Xiaoqiang Zhu for helpful discussion, and Guicheng Wang, Yanyan Nie, Xiaorong Huang, and Zhiyan Xia for technical assistance. This study was supported by grants from the National Natural Science Foundation of China (81270763), Chinese Hi-Tech Research and Development Project (2014AA021104), Chinese Key Projects for Basic Research (2011CB944001), Shanghai Municipal Government (15XD1500500 and 12431900100), and the Research Fund of the State Key Laboratory of Genetic Engineering, Fudan University. NR 31 TC 0 Z9 0 U1 3 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5498 EI 1557-7430 J9 DNA CELL BIOL JI DNA Cell Biol. PD OCT PY 2016 VL 35 IS 10 BP 585 EP 590 DI 10.1089/dna.2015.3022 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA DZ2DV UT WOS:000385653400004 PM 27383418 ER PT J AU Woloshchuk, CJ Nelson, KH Rice, KC Riley, AL AF Woloshchuk, Claudia J. Nelson, Katharine H. Rice, Kenner C. Riley, Anthony L. TI Effects of 3,4-methylenedioxypyrovalerone (MDPV) pre-exposure on the aversive effects of MDPV, cocaine and lithium chloride: Implications for abuse vulnerability SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE MDPV; Cocaine; LiCl; Conditioned taste avoidance; Drug pre-exposure ID INTRACRANIAL SELF-STIMULATION; CONDITIONED PLACE PREFERENCE; TASTE-AVERSION; BATH SALTS; CONSTITUENT 3,4-METHYLENEDIOXYPYROVALERONE; DESIGNER CATHINONES; LOCOMOTOR-ACTIVITY; RAT STRAINS; MEPHEDRONE; MICE AB Background: Drug use is thought to be a balance of the rewarding and aversive effects of drugs. Understanding how various factors impact these properties and their relative balance may provide insight into their abuse potential. In this context, the present study attempted to evaluate the effects of drug history on the aversive effects of 3,4-methylenedioxypyrovalerone (MDPV), one of a variety of synthetic cathinones (collectively known as "bath salts"). Methods: Different groups of male Sprague-Dawley rats were exposed to either vehicle or MDPV (1.8 mg/kg) once every fourth day for five total injections prior to taste avoidance conditioning in which a novel saccharin solution was repeatedly paired with either vehicle, MDPV (1.8 mg/kg), the related psychostimulant cocaine (18 mg/kg) or the emetic lithium chloride (LiCl) (13.65 mg/kg). Results: In animals pre-exposed to vehicle, all three drugs induced significant and comparable taste avoidance relative to animals injected with vehicle during conditioning. MDPV pre-exposure attenuated the avoidance induced by both MDPV and cocaine (greater attenuation for MDPV than cocaine), but had no effect on that induced by LiCl. Conclusions: These findings suggest that a history of MDPV use may reduce or attenuate MDPV and cocaine's (but not Lid 's) aversive effects. The implications for such changes in MDPV's aversive effects to its potential use and abuse were discussed. (C) 2016 Elsevier Ireland Ltd. All rights reserved. C1 [Woloshchuk, Claudia J.; Nelson, Katharine H.; Riley, Anthony L.] Amer Univ, Ctr Behav Neurosci, Psychopharmacol Lab, 4400 Massachusetts Ave NW, Washington, DC 20016 USA. [Rice, Kenner C.] NIDA, Mol Targets & Medicat Discovery Branch, NIAAA, Bethesda, MD 20892 USA. RP Woloshchuk, CJ (reprint author), Amer Univ, Ctr Behav Neurosci, Psychopharmacol Lab, 4400 Massachusetts Ave NW, Washington, DC 20016 USA. EM cw2606a@student.american.edu; alriley@american.edu FU Mellon Foundation FX This research was supported in part by a grant from the Mellon Foundation to ALR. The Mellon Foundation had no further role in the study design, data collection, analysis and interpretation, the writing of the report or the decision to submit the manuscript for publication. NR 65 TC 0 Z9 0 U1 1 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 OCT 1 PY 2016 VL 167 BP 121 EP 127 DI 10.1016/j.drugalcdep.2016.08.008 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA DY7QT UT WOS:000385325100017 PM 27520883 ER PT J AU Heinssen, R McGorry, P Nordentoft, M AF Heinssen, Robert McGorry, Patrick Nordentoft, Merete TI RAISE 2.0-Establishing a National Early Psychosis Intervention Network in the US SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Meeting Abstract C1 [Heinssen, Robert] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. [McGorry, Patrick] Univ Melbourne, Ctr Youth Mental Hlth, Orygen, Parkville, Vic, Australia. [Nordentoft, Merete] Univ Copenhagen, Mental Hlth Serv Capital Reg Denmark, DK-1168 Copenhagen, Denmark. 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 1751-7885 EI 1751-7893 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD OCT PY 2016 VL 10 SU 1 BP 4 EP 4 PG 1 WC Psychiatry SC Psychiatry GA DZ1EX UT WOS:000385582800004 ER PT J AU Adelsheim, S Harrison, V Heinssen, R Lowe, JI Blau, GM AF Adelsheim, Steven Harrison, Vicki Heinssen, Robert Lowe, Jane Isaacs Blau, Gary M. TI Implementation of a National Early Psychosis Clinical Support Program in the United States: The Prodrome and Early Psychosis Program Network (PEPPNET) SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Meeting Abstract C1 [Adelsheim, Steven; Harrison, Vicki] Stanford Univ, Palo Alto, CA 94304 USA. [Heinssen, Robert] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. [Lowe, Jane Isaacs] Robert Wood Johnson Fdn, Princeton, NJ 08540 USA. [Blau, Gary M.] Subst Abuse & Mental Hlth Serv Adm, Ctr Mental Hlth Serv, Rockville, 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 1751-7885 EI 1751-7893 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD OCT PY 2016 VL 10 SU 1 BP 23 EP 23 PG 1 WC Psychiatry SC Psychiatry GA DZ1EX UT WOS:000385582800062 ER PT J AU Addington, J Cadenhead, KS Cannon, TD Cornblatt, BA McGlashan, TH Perkins, DO Seidman, LJ Walker, EF Woods, S Bearden, CE Mathalon, D Buchy, L AF Addington, Jean Cadenhead, Kristin S. Cannon, Tyrone D. Cornblatt, Barbara A. McGlashan, Thomas H. Perkins, Diana O. Seidman, Larry J. Walker, Elaine F. Woods, Scott Bearden, Carrie E. Mathalon, Daniel Buchy, Lisa TI Cannabis Use in Individuals at Clinical High Risk of Psychosis SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Meeting Abstract C1 [Addington, Jean; Buchy, Lisa] Univ Calgary, Calgary, AB T2N 1N4, Canada. [Cadenhead, Kristin S.] Univ Calif San Diego, San Diego, CA 92103 USA. [Cannon, Tyrone D.; McGlashan, Thomas H.; Woods, Scott] Yale Univ, New Haven, CT USA. [Cornblatt, Barbara A.] Zucker Hillside Hosp, New York, NY USA. [Perkins, Diana O.] Univ N Carolina, Chapel Hill, NC 27515 USA. [Seidman, Larry J.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Seidman, Larry J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Walker, Elaine F.] Emory Univ, Atlanta, GA 30322 USA. NIMH, Bethesda, MD 20892 USA. [Bearden, Carrie E.] Univ Calif Los Angeles, Los Angeles, CA USA. [Mathalon, Daniel] Univ Calif San Francisco, San Francisco, CA 94143 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 1751-7885 EI 1751-7893 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD OCT PY 2016 VL 10 SU 1 BP 30 EP 30 PG 1 WC Psychiatry SC Psychiatry GA DZ1EX UT WOS:000385582800084 ER PT J AU Adelsheim, S Harrison, V Heinssen, R Lowe, JI Blau, GM AF Adelsheim, Steven Harrison, Vicki Heinssen, Robert Lowe, Jane Isaacs Blau, Gary M. TI Creating a National Early Psychosis Clinical Support Program in the United States: The Development of the Prodrome and Early Psychosis Program Network (PEPPNET) SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Meeting Abstract C1 [Adelsheim, Steven; Harrison, Vicki] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Heinssen, Robert] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. [Lowe, Jane Isaacs] Robert Wood Johnson Fdn, Program Dev, Princeton, NJ 08540 USA. [Blau, Gary M.] Subst Abuse & Mental Hlth Serv Adm, Ctr Mental Hlth Serv, 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 1751-7885 EI 1751-7893 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD OCT PY 2016 VL 10 SU 1 BP 99 EP 99 PG 1 WC Psychiatry SC Psychiatry GA DZ1EX UT WOS:000385582800295 ER PT J AU Schooler, N Mueser, K Estroff, S Correll, C Robinson, D Marcy, P Severe, J Azrin, S Goldstein, A Heinssen, R Kane, J AF Schooler, Nina Mueser, Kim Estroff, Sue Correll, Christoph Robinson, Delbert Marcy, Patricia Severe, Joanne Azrin, Susan Goldstein, Amy Heinssen, Robert Kane, John TI Elements of Recovery in First Episode Psychosis: Developing Measurable Criteria SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Meeting Abstract C1 [Schooler, Nina; Kane, John] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. [Mueser, Kim] Boston Univ, Boston, MA 02215 USA. [Estroff, Sue] Univ N Carolina, Chapel Hill, NC USA. [Correll, Christoph; Robinson, Delbert] Zucker Hillside Hosp, New York, NY USA. [Correll, Christoph; Robinson, Delbert; Marcy, Patricia] Northwell Hlth Syst NY, Great Neck, NY USA. [Severe, Joanne; Azrin, Susan; Goldstein, Amy; Heinssen, Robert] NIMH, 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 1751-7885 EI 1751-7893 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD OCT PY 2016 VL 10 SU 1 MA A106 BP 149 EP 149 PG 1 WC Psychiatry SC Psychiatry GA DZ1EX UT WOS:000385582800445 ER PT J AU Vyas, NS Lehrer, DS Merrill, B DeCastro, A Doninger, NA Christian, BT Buchsbaum, MS AF Vyas, Nora S. Lehrer, Douglas S. Merrill, Brian DeCastro, Alex Doninger, Nicholas A. Christian, Bradley T. Buchsbaum, Monte S. TI D2/D3 Dopamine Receptor Binding with [F-18] fallypride correlates of executive function in medication-naive patients with schizophrenia SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Meeting Abstract C1 [Vyas, Nora S.] Kingston Univ London, Kingston Upon Thames, Surrey, England. [Vyas, Nora S.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Vyas, Nora S.] Imperial Coll Healthcare NHS Trust, London, England. [Lehrer, Douglas S.; Merrill, Brian] Wright State Univ, Dayton, OH 45435 USA. [DeCastro, Alex; Buchsbaum, Monte S.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Doninger, Nicholas A.] Wright State Univ, SOM, Dayton, OH 45435 USA. [Christian, Bradley T.] Univ Wisconsin, Madison, WI 53706 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 1751-7885 EI 1751-7893 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD OCT PY 2016 VL 10 SU 1 BP 246 EP 246 PG 1 WC Psychiatry SC Psychiatry GA DZ1EX UT WOS:000385582800758 ER PT J AU Hoffmann, GR Shelby, MD Zeiger, E AF Hoffmann, George R. Shelby, Michael D. Zeiger, Errol TI Remembering Heinrich Malling In Memoriam SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Biographical-Item C1 [Hoffmann, George R.] Coll Holy Cross, Dept Biol, One Coll St, Worcester, MA 01610 USA. [Shelby, Michael D.] NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. [Zeiger, Errol] Errol Zeiger Consulting, Chapel Hill, NC 27514 USA. RP Hoffmann, GR (reprint author), Coll Holy Cross, Dept Biol, One Coll St, Worcester, MA 01610 USA. EM ghoffmann@holycross.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD OCT PY 2016 VL 57 IS 8 BP 575 EP 578 DI 10.1002/em.22056 PG 4 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA DZ4OA UT WOS:000385836800001 PM 27696552 ER PT J AU Dai, YF Niu, Y Duan, HW Bassig, BA Ye, M Zhang, X Meng, T Bin, P Jia, XW Shen, ML Zhang, R Hu, W Yang, XF Vermeulen, R Silverman, D Rothman, N Lan, Q Yu, SF Zheng, YX AF Dai, Yufei Niu, Yong Duan, Huawei Bassig, Bryan A. Ye, Meng Zhang, Xiao Meng, Tao Bin, Ping Jia, Xiaowei Shen, Meili Zhang, Rong Hu, Wei Yang, Xiaofa Vermeulen, Roel Silverman, Debra Rothman, Nathaniel Lan, Qing Yu, Shanfa Zheng, Yuxin TI Effects of occupational exposure to carbon black on peripheral white blood cell counts and lymphocyte subsets SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE carbon black; occupational exposure; inflammation; immunotoxicity ID LUNG-CANCER; PARTICULATE MATTER; INHALED PARTICLES; COHORT MORTALITY; DIESEL EXHAUST; AIR-POLLUTION; INFLAMMATION; WORKERS; HEALTH; DISEASE AB The International Agency for Research on Cancer has classified carbon black (CB) as a possible (Group 2B) human carcinogen. Given that most CB manufacturing processes result in the emission of various types of chemicals, it is uncertain if the adverse health effects that have been observed in CB-exposed workers are related to CB specifically or are due to other exposures. To address this issue, we conducted a cross-sectional molecular epidemiology study in China of 106 male factory workers who were occupationally exposed to pure CB and 112 unexposed male workers frequency-matched by age and smoking status from the same geographic region. Repeated personal exposure measurements were taken in workers before biological sample collection. Peripheral blood from all workers was used for the complete blood cell count and lymphocyte subsets analysis. Compared to unexposed workers, eosinophil counts in workers exposed to CB were increased by 30.8% (P=0.07) after adjusting for potential confounders. When stratified by smoking status, statistically significant differences in eosinophils between CB exposed and unexposed workers were only present among never smokers (P=0.040). Smoking is associated with alterations in various cell counts; however, no significant interaction between CB exposure and smoking status for any cell counts was observed. Given that inflammation, characterized in part by elevated eosinophils in peripheral blood, may be associated with increased cancer risk, our findings provide new biologic insights into the potential relationship between CB exposure and lung carcinogenesis. Environ. Mol. Mutagen. 57:589-604, 2016. (c) 2016 Wiley Periodicals, Inc. C1 [Dai, Yufei; Niu, Yong; Duan, Huawei; Ye, Meng; Zhang, Xiao; Meng, Tao; Bin, Ping; Jia, Xiaowei; Shen, Meili; Zhang, Rong; Zheng, Yuxin] Chinese Ctr Dis Control & Prevent, Natl Inst Occupat Hlth & Poison Control, Key Lab, Beijing 100050, Peoples R China. [Dai, Yufei; Bassig, Bryan A.; Hu, Wei; Silverman, Debra; Rothman, Nathaniel; Lan, Qing] NCI, Occupat & Environm Epidemiol Branch, Rockville, MD 20850 USA. [Zhang, Rong] Hebei Med Univ, Dept Toxicol, Sch Publ Hlth, Shijiazhuang, Peoples R China. [Yang, Xiaofa] Jiao Zuo Ctr Dis Control & Prevent, Jiaozuo, Peoples R China. [Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Div Environm Epidemiol, Utrecht, Netherlands. [Yu, Shanfa] Henan Prov Inst Occupat Hlth, Zhengzhou, Peoples R China. RP Lan, Q (reprint author), NCI, Occupat & Environm Epidemiol Branch, Rockville, MD 20850 USA.; Yu, SF (reprint author), Henan Prov Inst Occupat Hlth, Zhengzhou, Peoples R China.; Zheng, YX (reprint author), Chinese Ctr Dis Control & Prevent, Natl Inst Occupat Hlth & Poison Control, Beijing 100050, Peoples R China. EM qingl@mail.nih.gov; yu-shanfa@163.com; zhengyx@chinacdc.cn RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 NR 42 TC 0 Z9 0 U1 6 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD OCT PY 2016 VL 57 IS 8 BP 615 EP 622 DI 10.1002/em.22036 PG 8 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA DZ4OA UT WOS:000385836800005 PM 27671983 ER PT J AU Dal-Re, R Rid, A Emanuel, E Wendler, D AF Dal-Re, Rafael Rid, Annette Emanuel, Ezekiel Wendler, David TI Addressing exploitation of poor clinical trial participants in North America and the European Union SO EUROPEAN JOURNAL OF INTERNAL MEDICINE LA English DT Letter DE Clinical research; Clinical trial regulations; Fair benefits; Poor participants; Uninsured patients C1 [Dal-Re, Rafael] Univ Autonoma Madrid, BUC Biosci UAM CSIC Program, Clin Res, Int Campus Excellence, Madrid, Spain. [Rid, Annette] Kings Coll London, Dept Social Sci Hlth & Med, London, England. [Emanuel, Ezekiel] Univ Penn, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. [Wendler, David] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Dal-Re, R (reprint author), Univ Autonoma Madrid, Invest Clin, Programa BUC Biociencias UAM CSIC, Campus Excelencia Int,Ciudad Univ Cantoblanco, E-28049 Madrid, Spain. EM Rafael.dalre@fuam.uam.es NR 10 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0953-6205 EI 1879-0828 J9 EUR J INTERN MED JI Eur. J. Intern. Med. PD OCT PY 2016 VL 34 BP E37 EP E38 DI 10.1016/j.ejim.2016.06.026 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA DY9XG UT WOS:000385488500018 PM 27425655 ER PT J AU Mead, B Tomarev, S AF Mead, Ben Tomarev, Stanislav TI Evaluating retinal ganglion cell loss and dysfunction SO EXPERIMENTAL EYE RESEARCH LA English DT Review DE Retina; Retinal ganglion cells; Electroretinography; Visual evoked potential; Quantification; Dysfunction ID OPTIC-NERVE CRUSH; PHOTOPIC NEGATIVE RESPONSE; RETROGRADE AXONAL-TRANSPORT; OCULAR HYPERTENSION MODEL; RNA-BINDING PROTEIN; OPEN-ANGLE GLAUCOMA; MOUSE MODEL; IN-VIVO; ADULT-RATS; ELECTROPHYSIOLOGICAL ASSESSMENT AB Retinal ganglion cells (RGC) bear the sole responsibility of propagating visual stimuli to the brain. Their axons, which make up the optic nerve, project from the retina to the brain through the lamina cribrosa and in rodents, decussate almost entirely at the optic chiasm before synapsing at the superior colliculus. For many traumatic and degenerative ocular conditions, the dysfunction and/or loss of RGC is the primary determinant of visual loss and are the measurable endpoints in current research into experimental therapies. To actually measure these endpoints in rodent models, techniques must ascertain both the quantity of surviving RGC and their functional capacity. Quantification techniques include phenotypic markers of RGC, retrogradely transported fluorophores and morphological measurements of retinal thickness whereas functional assessments include electroretinography (flash and pattern) and visual evoked potential. The importance of the accuracy and reliability of these techniques cannot be understated, nor can the relationship between RGC death and dysfunction. The existence of up to 30 types of RGC complicates the measuring process, particularly as these may respond differently to disease and treatment. Since the above techniques may selectively identify and ignore particular subpopulations, their appropriateness as measures of RGC survival and function may be further limited. This review discusses the above techniques in the context of their subtype specificity. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Mead, Ben; Tomarev, Stanislav] NEI, Sect Retinal Gangl Cell Biol, Lab Retinal Cell & Mol Biol, NIH, 6 Ctr Dr,Bldg 6,Room 213B, Bethesda, MD 20892 USA. RP Mead, B (reprint author), NEI, Sect Retinal Gangl Cell Biol, Lab Retinal Cell & Mol Biol, NIH, 6 Ctr Dr,Bldg 6,Room 213B, Bethesda, MD 20892 USA. EM ben.mead@nih.gov FU National Eye Institute Intramural Research Program FX This work was funded by a grant from the National Eye Institute Intramural Research Program. NR 113 TC 1 Z9 1 U1 12 U2 12 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 EI 1096-0007 J9 EXP EYE RES JI Exp. Eye Res. PD OCT PY 2016 VL 151 BP 96 EP 106 DI 10.1016/j.exer.2016.08.006 PG 11 WC Ophthalmology SC Ophthalmology GA DZ1OI UT WOS:000385607300014 PM 27523467 ER PT J AU Dreger, DL Davis, BW Cocco, R Sechi, S Di Cerbo, A Parker, HG Polli, M Marelli, SP Crepaldi, P Ostrander, EA AF Dreger, Dayna L. Davis, Brian W. Cocco, Raffaella Sechi, Sara Di Cerbo, Alessandro Parker, Heidi G. Polli, Michele Marelli, Stefano P. Crepaldi, Paola Ostrander, Elaine A. TI Commonalities in Development of Pure Breeds and Population Isolates Revealed in the Genome of the Sardinian Fonni's Dog SO GENETICS LA English DT Article DE dog; whole-genome sequence; demography; population structure ID BARDET-BIEDL-SYNDROME; HEREDITARY PROSTATE-CANCER; OLD ORDER AMISH; DOMESTIC DOG; LINKAGE DISEQUILIBRIUM; GENETIC-STRUCTURE; SEQUENCING DATA; WIDE SEARCH; SNP DATA; DISEASE AB The island inhabitants of Sardinia have long been a focus for studies of complex human traits due to their unique ancestral background and population isolation reflecting geographic and cultural restriction. Population isolates share decreased genomic diversity, increased linkage disequilibrium, and increased inbreeding coefficients. In many regions, dogs and humans have been exposed to the same natural and artificial forces of environment, growth, and migration. Distinct dog breeds have arisen through human-driven selection of characteristics to meet an ideal standard of appearance and function. The Fonni's Dog, an endemic dog population on Sardinia, has not been subjected to an intensive system of artificial selection, but rather has developed alongside the human population of Sardinia, influenced by geographic isolation and unregulated selection based on its environmental adaptation and aptitude for owner-desired behaviors. Through analysis of 28 dog breeds, represented with whole-genome sequences from 13 dogs and similar to 170,000 genome-wide single nucleotide variants from 155 dogs, we have produced a genomic illustration of the Fonni's Dog. Genomic patterns confirm within-breed similarity, while population and demographic analyses provide spatial identity of Fonni's Dog to other Mediterranean breeds. Investigation of admixture and fixation indices reveals insights into the involvement of Fonni's Dogs in breed development throughout the Mediterranean. We describe how characteristics of population isolates are reflected in dog breeds that have undergone artificial selection, and are mirrored in the Fonni's Dog through traditional isolating factors that affect human populations. Lastly, we show that the genetic history of Fonni's Dog parallels demographic events in local human populations. C1 [Dreger, Dayna L.; Davis, Brian W.; Parker, Heidi G.; Ostrander, Elaine A.] NHGRI, Canc Genet & Comparat Genom Branch, NIH, Bethesda, MD 20892 USA. [Cocco, Raffaella; Sechi, Sara] Univ Sassari, Dipartimento Med Vet, Sez Clin Med, I-07100 Sassari, Italy. [Di Cerbo, Alessandro] Univ G dAnnunzio, Specializzaz Biochim Clin, Dipartimento Sci Med Orali & Biotecnol, I-66100 Chieti, Italy. [Polli, Michele; Marelli, Stefano P.; Crepaldi, Paola] Univ Milan, Dipartimento Med Vet, I-20133 Milan, Italy. RP Ostrander, EA (reprint author), NHGRI, NIH, Bldg 50,Room 5351,50 South Dr, Bethesda, MD 20892 USA. EM eostrand@mail.nih.gov OI Ostrander, Elaine/0000-0001-6075-9738 FU Intramural Program of the International Human Genome Research Institute; misura 3.13 del Programma Operativo Regione (P.O.R.) Sardegna (Fondi Europep di Sviluppo Regionale (FESR)) FX The authors thank all the dog owners and their dogs for providing DNA samples. Special thanks to Sir Terence Clark, Mauricio Lima, and Robert Gennari for obtaining DNA samples from regional dog breeds from Italy, North Africa, and the Middle East. D.L.D., E.A.O, B.W.D, and H.G.P. acknowledge support from the Intramural Program of the International Human Genome Research Institute. This study is part of an Italian study "Detection of morphological, genetic, and behavioral characteristics of Fonni's Dog, aimed at selection and official recognition of this breed by ENCI", funded in part by misura 3.13 del Programma Operativo Regione (P.O.R.) Sardegna 2006-2008 (Fondi Europep di Sviluppo Regionale (FESR)). NR 76 TC 0 Z9 0 U1 14 U2 14 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 OCT PY 2016 VL 204 IS 2 BP 737 EP 755 DI 10.1534/genetics.116.192427 PG 19 WC Genetics & Heredity SC Genetics & Heredity GA DZ4ZP UT WOS:000385871400028 PM 27519604 ER PT J AU Rehman, AU Bird, JE Faridi, R Shahzad, M Shah, S Lee, K Khan, SN Imtiaz, A Ahmed, ZM Riazuddin, S Santos-Cortez, RLP Ahmad, W Leal, SM Riazuddin, S Friedman, TB AF Rehman, Atteeq U. Bird, Jonathan E. Faridi, Rabia Shahzad, Mohsin Shah, Sujay Lee, Kwanghyuk Khan, Shaheen N. Imtiaz, Ayesha Ahmed, Zubair M. Riazuddin, Saima Santos-Cortez, Regie Lyn P. Ahmad, Wasim Leal, Suzanne M. Riazuddin, Sheikh Friedman, Thomas B. TI Mutational Spectrum of MYO15A and the Molecular Mechanisms of DFNB3 Human Deafness SO HUMAN MUTATION LA English DT Article DE DFNB3; deafness; myosin 15; MYO15A; shaker 2; giant exon; micro exon ID NONSYNDROMIC HEARING-LOSS; HAIR-CELL STEREOCILIA; MYOSIN-VIIA GENE; TARGETED GENOMIC CAPTURE; NON-SYNDROMIC DEAFNESS; RECESSIVE DEAFNESS; UNCONVENTIONAL MYOSIN; PROFOUND DEAFNESS; USHER-SYNDROME; STEM-CELLS AB Deafness in humans is a common neurosensory disorder and is genetically heterogeneous. Across diverse ethnic groups, mutations of MYO15A at the DFNB3 locus appear to be the third or fourth most common cause of autosomal-recessive, nonsyndromic deafness. In 49 of the 67 exons of MYO15A, there are currently 192 recessive mutations identified, including 14 novel mutations reported here. These mutations are distributed uniformly across MYO15A with one enigmatic exception; the alternatively spliced giant exon 2, encoding 1,233 residues, has 17 truncating mutations but no convincing deafness-causing missense mutations. MYO15A encodes three distinct isoform classes, one of which is 395 kDa (3,530 residues), the largest member of the myosin superfamily of molecular motors. Studies of Myo15 mouse models that recapitulate DFNB3 revealed two different pathogenic mechanisms of hearing loss. In the inner ear, myosin 15 is necessary both for the development and the long-term maintenance of stereocilia, mechanosensory sound-transducing organelles that extend from the apical surface of hair cells. The goal of this Mutation Update is to provide a comprehensive review of mutations and functions of MYO15A. (C) 2016 Wiley Periodicals, Inc. C1 [Rehman, Atteeq U.; Bird, Jonathan E.; Faridi, Rabia; Shah, Sujay; Imtiaz, Ayesha; Friedman, Thomas B.] Natl Inst Deafness & Other Commun Disorders, Lab Mol Genet, NIH, Bethesda, MD 20892 USA. [Faridi, Rabia; Khan, Shaheen N.] Univ Punjab, Ctr Excellence Mol Biol, Lahore 54550, Pakistan. [Shahzad, Mohsin; Ahmed, Zubair M.; Riazuddin, Saima] Univ Maryland, Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Baltimore, MD 21201 USA. [Lee, Kwanghyuk; Santos-Cortez, Regie Lyn P.; Leal, Suzanne M.] Baylor Coll Med, Dept Mol & Human Genet, Ctr Stat Genet, Houston, TX 77030 USA. [Ahmad, Wasim] Quaid I Azam Univ, Fac Biol Sci, Dept Biochem, Islamabad 45320, Pakistan. [Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Res Ctr, Jinnah Hosp Complex, Lahore 54550, Pakistan. [Rehman, Atteeq U.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Friedman, TB (reprint author), Natl Inst Deafness & Other Commun Disorders, Lab Mol Genet, NIH, Bethesda, MD 20892 USA. EM friedman@nidcd.nih.gov OI Bird, Jonathan/0000-0001-5531-8794 FU Intramural Research Program of the NIDCD/NIH [DC000048-19]; Higher Education Commission of Pakistan (HEC); NIDCD [R01 DC003594, R01 DC011651, R01DC012564, R01DC011803] FX Contract grant sponsors: Intramural Research Program of the NIDCD/NIH (DC000048-19); Higher Education Commission of Pakistan (HEC); NIDCD (grants R01 DC003594, R01 DC011651, R01DC012564, R01DC011803). NR 106 TC 2 Z9 2 U1 5 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-7794 EI 1098-1004 J9 HUM MUTAT JI Hum. Mutat. PD OCT PY 2016 VL 37 IS 10 BP 991 EP 1003 DI 10.1002/humu.23042 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA DZ4CQ UT WOS:000385805800013 PM 27375115 ER PT J AU Olfson, M Blanco, C Marcus, SC AF Olfson, Mark Blanco, Carlos Marcus, Steven C. TI Treatment of Adult Depression in the United States SO JAMA INTERNAL MEDICINE LA English DT Article ID COMORBIDITY SURVEY REPLICATION; SERIOUS MENTAL-ILLNESS; HEALTH-CARE; GENERAL-POPULATION; MAJOR DEPRESSION; NATIONAL TRENDS; METAANALYSIS; PSYCHOTHERAPY; DISORDER; SETTINGS AB IMPORTANCE Despite recent increased use of antidepressants in the United States, concerns persist that many adults with depression do not receive treatment, whereas others receive treatments that do not match their level of illness severity. OBJECTIVE To characterize the treatment of adult depression in the United States. DESIGN, SETTING, AND PARTICIPANTS Analysis of screen-positive depression, psychological distress, and depression treatment data from 46 417 responses to the Medical Expenditure Panel Surveys taken in US households by participants aged 18 years or older in 2012 and 2013. MAIN OUTCOME AND MEASURES Percentages of adults with screen-positive depression (Patient Health Questionnaire-2 score of > 3) and adjusted odds ratios (AORs) of the effects of sociodemographic characteristics on odds of screen-positive depression; percentages with treatment for screen-positive depression and AORs; percentages with any treatment of depression and AORs stratified by presence of serious psychological distress (Kessler 6 scale score of >= 13); and percentages with depression treatment by health care professional group (psychiatrists, other health care professionals, and general medical providers); and type of depression treatment (antidepressants, psychotherapy, and both) all stratified by distress level. RESULTS Approximately 8.4%(95% CI, 7.9-8.8) of adults screened positive for depression, of which 28.7% received any depression treatment. Conversely, among all adults treated for depression, 29.9% had screen-positive depression and 21.8% had serious psychological distress. Adults with serious compared with less serious psychological distress who were treated for depression were more likely to receive care from psychiatrists (33.4% vs 17.3%, P < .001) or other mental health specialists (16.2% vs 9.6%, P < .001), and less likely to receive depression care exclusively from general medical professionals (59.0% vs 74.4%, P < .001). They were also more likely to receive psychotherapy (32.5% vs 20.6%, P < .001), though not antidepressant medications (81.1% vs 88.6%, P < .001). CONCLUSIONS AND RELEVANCE Most US adults who screen positive for depression did not receive treatment for depression, whereas most who were treated did not screen positive. In light of these findings, it is important to strengthen efforts to align depression care with each patient's clinical needs. C1 [Olfson, Mark] Columbia Univ Coll Phys & Surg, Dept Psychiat, 722 W 168th St, New York, NY 10032 USA. [Olfson, Mark] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Blanco, Carlos] NIDA, Bethesda, MD 20892 USA. [Marcus, Steven C.] Univ Penn, Sch Social Practice & Policy, Philadelphia, PA 19104 USA. RP Olfson, M (reprint author), Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, 1051 Riverside Dr, New York, NY 10032 USA. EM mo49@cumc.columbia.edu FU Agency for Healthcare Quality and Research [U19 HS02112]; National Institute on Drug Abuse; AHRQ FX This work was supported by the Agency for Healthcare Quality and Research U19 HS02112. Work by Dr. Blanco was supported by the National Institute on Drug Abuse and he had no role in the grant from AHRQ. NR 50 TC 5 Z9 5 U1 10 U2 10 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 OCT PY 2016 VL 176 IS 10 BP 1482 EP 1491 DI 10.1001/jamainternmed.2016.5057 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA DZ1ZU UT WOS:000385642000013 PM 27571438 ER PT J AU Goedert, JJ AF Goedert, James J. TI Intestinal Microbiota and Health of Adults Who Were Born by Cesarean Delivery SO JAMA PEDIATRICS LA English DT Letter C1 [Goedert, James J.] NCI, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,Room 6E106,MSC 9767, Bethesda, MD 20892 USA. RP Goedert, JJ (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,Room 6E106,MSC 9767, Bethesda, MD 20892 USA. EM goedertj@mail.nih.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6203 EI 2168-6211 J9 JAMA PEDIATR JI JAMA Pediatr. PD OCT PY 2016 VL 170 IS 10 BP 1027 EP 1027 DI 10.1001/jamapediatrics.2016.2310 PG 1 WC Pediatrics SC Pediatrics GA DZ2AB UT WOS:000385643000026 PM 27548071 ER PT J AU Blanco, C Compton, WM Grant, BF AF Blanco, Carlos Compton, Wilson M. Grant, Bridget F. TI Toward Precision Epidemiology SO JAMA PSYCHIATRY LA English DT Editorial Material ID COMMON PSYCHIATRIC-DISORDERS; GENERAL-POPULATION; ANXIETY DISORDERS; MENTAL-DISORDERS; DEPRESSION; ILLNESS; ALCOHOL; SAMPLE C1 [Blanco, Carlos] NIDA, Div Epidemiol Serv & Prevent Res, 6001 Execut Blvd, Bethesda, MD 20852 USA. [Compton, Wilson M.] NIDA, Off Director, Bethesda, MD 20892 USA. [Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, Rockville, MD 20852 USA. RP Blanco, C (reprint author), NIDA, Div Epidemiol Serv & Prevent Res, 6001 Execut Blvd, Bethesda, MD 20852 USA. EM carlos.blanco2@nih.gov NR 16 TC 1 Z9 1 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD OCT PY 2016 VL 73 IS 10 BP 1008 EP 1009 DI 10.1001/jamapsychiatry.2016.1869 PG 2 WC Psychiatry SC Psychiatry GA DZ5QG UT WOS:000385916000003 PM 27603943 ER PT J AU Paksarian, D Cui, LH Angst, J Ajdacic-Gross, V Rossler, W Merikangas, KR AF Paksarian, Diana Cui, Lihong Angst, Jules Ajdacic-Gross, Vladeta Rossler, Wulf Merikangas, Kathleen R. TI Latent Trajectories of Common Mental Health Disorder Risk Across 3 Decades of Adulthood in a Population-Based Cohort SO JAMA PSYCHIATRY LA English DT Article ID EPIDEMIOLOGIC CATCHMENT-AREA; NATIONAL-COMORBIDITY-SURVEY; SUBSTANCE USE DISORDERS; OF-ONSET DISTRIBUTIONS; UNITED-STATES; LIFETIME PREVALENCE; FOLLOW-UP; PSYCHIATRIC-DISORDERS; DEPRESSIVE DISORDER; ZURICH COHORT AB IMPORTANCE Epidemiologic evidence indicates that most of the general population will experience a mental health disorder at some point in their lives. However, few prospective population-based studies have estimated trajectories of risk for mental disorders from young through middle adulthood to estimate the proportion of individuals who experience persistent mental disorder across this age period. OBJECTIVES To describe the proportion of the population who experience persistent mental disorder across adulthood and to estimate latent trajectories of disorder risk across this age period. DESIGN, SETTING, AND PARTICIPANTS A population-based, prospective cohort study was conducted between 1979 and 2008 in the canton of Zurich, Switzerland. A stratified random sample of 591 Swiss citizens was enrolled in 1978 at ages 19 years (men) and 20 years (women); 7 interviews were performed during a 29-year period. Men were sampled from military enrollment records and women from electoral records. From those initially enrolled, participants with high levels of psychiatric symptoms were oversampled for follow-up. Data analysis was performed from July 28, 2015, to June 8, 2016. MAIN OUTCOMES AND MEASURES Latent trajectories, estimated using growth mixture modeling, of past-year mood/anxiety disorder (ie, major depressive episode, phobias, panic, generalized anxiety disorder, and obsessive-compulsive disorder), substance use disorder (ie, drug abuse or dependence and alcohol abuse or dependence), and any mental disorder (ie, any of the above) assessed during in-person semistructured interviews at each wave. Diagnoses were based on DSM-III, DSM-III-R, and DSM-IV criteria. RESULTS Of the 591 participants at baseline, 299 (50.6%) were female. Persistent mental health disorder across multiple study waves was rare. Among 252 individuals (42.6%) who participated in all 7 study waves, only 1.2% met criteria for disorder every time. Growth mixture modeling identified 3 classes of risk for any disorder across adulthood: low (estimated prevalence, 40.0%; 95% CI, -8.7% to 88.9%), increasing-decreasing (estimated prevalence, 15.3%; 95% CI, 1.0% to 29.6%), and increasing (estimated prevalence, 44.7%; 95% CI, -0.9% to 90.1%). Although no classes were characterized by persistently high disorder risk, for those in the increasing-decreasing class, risk was high from the late 20s to early 40s. Sex-specific models indicated 4 trajectory classes for women but only 3 for men. CONCLUSIONS AND RELEVANCE Persistently high mental health disorder risk across 3 decades of adulthood was rare in this population-based sample. Identifying early determinants of sex-specific risk trajectories would benefit prevention efforts. C1 [Paksarian, Diana; Cui, Lihong; Merikangas, Kathleen R.] NIMH, Genet Epidemiol Res Branch, Intramural Res Program, Bethesda, MD 20892 USA. [Angst, Jules; Ajdacic-Gross, Vladeta] Univ Zurich, Hosp Psychiat, Dept Psychiat Psychotherapy & Psychosomat, Zurich, Switzerland. [Rossler, Wulf] Univ Sao Paulo, Inst Psychiat, Lab Neurosci, Sao Paulo, Brazil. [Rossler, Wulf] Univ Zurich, Coll Helveticum, Zurich, Switzerland. [Rossler, Wulf] Swiss Tech Inst, Zurich, Switzerland. RP Merikangas, KR (reprint author), NIMH, Genet Epidemiol Res Branch, 35A Convent Dr,MSC 3720, Bethesda, MD 20892 USA. EM kathleen.merikangas@nih.gov FU Intramural Research Program of the National Institute of Mental Health [ZIAMH002807]; Swiss National Science Foundation [3200-050881.97/1, 32-50881.97] FX This study was supported by project ZIAMH002807 from the Intramural Research Program of the National Institute of Mental Health and grants 3200-050881.97/1 and 32-50881.97 from the Swiss National Science Foundation. NR 59 TC 1 Z9 1 U1 14 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD OCT PY 2016 VL 73 IS 10 BP 1023 EP 1031 DI 10.1001/jamapsychiatry.2016.1921 PG 9 WC Psychiatry SC Psychiatry GA DZ5QG UT WOS:000385916000007 PM 27602550 ER PT J AU Pongracic, JA Krouse, RZ Babineau, DC Zoratti, EM Cohen, RT Wood, RA Hershey, GKK Kercsmar, CM Gruchalla, RS Kattan, M Teach, SJ Johnson, CC Bacharier, LB Gern, JE Sigelman, SM Gergen, PJ Togias, A Visness, CM Busse, WW Liu, AH AF Pongracic, Jacqueline A. Krouse, Rebecca Z. Babineau, Denise C. Zoratti, Edward M. Cohen, Robyn T. Wood, Robert A. Hershey, Gurjit K. Khurana Kercsmar, Carolyn M. Gruchalla, Rebecca S. Kattan, Meyer Teach, Stephen J. Johnson, Christine C. Bacharier, Leonard B. Gern, James E. Sigelman, Steven M. Gergen, Peter J. Togias, Alkis Visness, Cynthia M. Busse, William W. Liu, Andrew H. TI Distinguishing characteristics of difficult-to-control asthma in inner-city children and adolescents SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Child; asthma; inner-city asthma; asthma phenotype; asthma morbidity; asthma severity; asthma exacerbations; pulmonary function; rhinitis; allergen sensitization; IgE ID ALLERGIC RHINITIS; BRONCHODILATOR RESPONSIVENESS; PRESCHOOL-CHILDREN; MODERATE ASTHMA; YOUNG-ADULTS; IMPACT; CHILDHOOD; OBSTRUCTION; VALIDATION; MANAGEMENT AB Background: Treatment levels required to control asthma vary greatly across a population with asthma. The factors that contribute to variability in treatment requirements of inner-city children have not been fully elucidated. Objective: We sought to identify the clinical characteristics that distinguish difficult-to-control asthma from easy-to-control asthma. Methods: Asthmatic children aged 6 to 17 years underwent baseline assessment and bimonthly guideline-based management visits over 1 year. Difficult-to-control and easy-to-control asthma were defined as daily therapy with 500 mg of fluticasone or greater with or without a long-acting beta-agonist versus 100 mu g or less assigned on at least 4 visits. Forty-four baseline variables were used to compare the 2 groups by using univariate analyses and to identify the most relevant features of difficult-to-control asthma by using a variable selection algorithm. Nonlinear seasonal variation in longitudinal measures (symptoms, pulmonary physiology, and exacerbations) was examined by using generalized additive mixed-effects models. Results: Among 619 recruited participants, 40.9% had difficult-to-control asthma, 37.5% had easy-to-control asthma, and 21.6% fell into neither group. At baseline, FEV1 bronchodilator responsiveness was the most important characteristic distinguishing difficult-to-control asthma from easy-to-control asthma. Markers of rhinitis severity and atopy were among the other major discriminating features. Over time, difficult-tocontrol asthma was characterized by high exacerbation rates, particularly in spring and fall; greater daytime and nighttime symptoms, especially in fall and winter; and compromised pulmonary physiology despite ongoing high-dose controller therapy. Conclusions: Despite good adherence, difficult-to-control asthma showed little improvement in symptoms, exacerbations, or pulmonary physiology over the year. In addition to pulmonary physiology measures, rhinitis severity and atopy were associated with high-dose asthma controller therapy requirement. C1 [Pongracic, Jacqueline A.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. [Krouse, Rebecca Z.; Babineau, Denise C.; Visness, Cynthia M.] Rho Fed Syst Div, Chapel Hill, NC USA. [Zoratti, Edward M.; Johnson, Christine C.] Henry Ford Hlth Syst, Detroit, MI USA. [Cohen, Robyn T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Wood, Robert A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Hershey, Gurjit K. Khurana; Kercsmar, Carolyn M.] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Gruchalla, Rebecca S.] Univ Texas Southwestern Med Ctr Dallas, Dallas, TX 75390 USA. [Kattan, Meyer] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Teach, Stephen J.] Childrens Natl Hlth Syst, Washington, DC USA. [Teach, Stephen J.] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA. [Bacharier, Leonard B.] St Louis Childrens Hosp, St Louis, MO 63178 USA. [Gern, James E.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Sigelman, Steven M.; Gergen, Peter J.; Togias, Alkis] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Liu, Andrew H.] Natl Jewish Hlth, Denver, CO USA. [Liu, Andrew H.] Childrens Hosp Colorado, Aurora, CO USA. [Liu, Andrew H.] Univ Colorado, Sch Med, Aurora, CO USA. RP Pongracic, JA (reprint author), 225 E Chicago Av 60, Chicago, IL 60614 USA. EM jpongracic@luriechildrens.org OI Cohen, Robyn/0000-0002-6902-3118 FU National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services [HHSN272200900052C, HHSN272201000052I, 1UM1AI114271-01]; National Center for Research Resources (NCRR); National Center for Advancing Translational Sciences (NCATS), NIH [NCRR/NIH UL1TR000451, UL1RR025780, UL1TR000075 Q1, NCATS/NIH UL1TR000154, UL1TR001082, UL1TR000077-04, UL1TR000040, UL1TR000150, UL1TR001105] FX This project has been funded in whole or in part with federal funds from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services (under contract nos. HHSN272200900052C and HHSN272201000052I, and 1UM1AI114271-01). Additional support was provided by the National Center for Research Resources (NCRR), and the National Center for Advancing Translational Sciences (NCATS), NIH (under grant nos. NCRR/NIH UL1TR000451, UL1RR025780, UL1TR000075 Q1 and NCATS/NIH UL1TR000154, UL1TR001082, UL1TR000077-04, UL1TR000040, UL1TR000150, and UL1TR001105). GlaxoSmithKline (GSK) provided Ventolin, Flovent, Advair, and Flonase under a clinical trial agreement with NIH NIAID; GSK did not have a role in the development or approval of the protocol, conduct of the trial, data analysis, manuscript preparation, or the decision to submit the manuscript for publication. NR 38 TC 4 Z9 4 U1 2 U2 2 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 OCT PY 2016 VL 138 IS 4 BP 1030 EP 1041 DI 10.1016/j.jaci.2016.06.059 PG 12 WC Allergy; Immunology SC Allergy; Immunology GA DZ0AP UT WOS:000385499400008 PM 27720017 ER PT J AU Liu, AH Babineau, DC Krouse, RZ Zoratti, EM Pongracic, JA O'Connor, GT Wood, RA Hershey, GKK Kercsmar, CM Gruchalla, RS Kattan, M Teach, SJ Makhija, M Pillai, D Lamm, CI Gern, JE Sigelman, SM Gergen, PJ Togias, A Visness, CM Busse, WW AF Liu, Andrew H. Babineau, Denise C. Krouse, Rebecca Z. Zoratti, Edward M. Pongracic, Jacqueline A. O'Connor, George T. Wood, Robert A. Hershey, Gurjit K. Khurana Kercsmar, Carolyn M. Gruchalla, Rebecca S. Kattan, Meyer Teach, Stephen J. Makhija, Melanie Pillai, Dinesh Lamm, Carin I. Gern, James E. Sigelman, Steven M. Gergen, Peter J. Togias, Alkis Visness, Cynthia M. Busse, William W. TI Pathways through which asthma risk factors contribute to asthma severity in inner-city children SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Asthma; children; inner-city; allergy; sensitization; inflammation; lung function; pulmonary physiology; rhinitis; environmental tobacco smoke exposure ID ALLERGIC RHINITIS; ADOLESCENTS; MORBIDITY; EXACERBATIONS; VALIDATION; EXPOSURE; VALIDITY; VIOLENCE; STRESS; IMPACT AB Background: Pathway analyses can be used to determine how host and environmental factors contribute to asthma severity. Objective: To investigate pathways explaining asthma severity in inner-city children. Methods: On the basis of medical evidence in the published literature, we developed a conceptual model to describe how 8 risk-factor domains (allergen sensitization, allergic inflammation, pulmonary physiology, stress, obesity, vitamin D, environmental tobacco smoke [ETS] exposure, and rhinitis severity) are linked to asthma severity. To estimate the relative magnitude and significance of hypothesized relationships among these domains and asthma severity, we applied a causal network analysis to test our model in an Inner-City Asthma Consortium study. Participants comprised 6- to 17-year-old children (n = 561) with asthma and rhinitis from 9 US inner cities who were evaluated every 2 months for 1 year. Asthma severity was measured by a longitudinal composite assessment of day and night symptoms, exacerbations, and controller usage. Results: Our conceptual model explained 53.4% of the variance in asthma severity. An allergy pathway (linking allergen sensitization, allergic inflammation, pulmonary physiology, and rhinitis severity domains to asthma severity) and the ETS exposure pathway (linking ETS exposure and pulmonary physiology domains to asthma severity) exerted significant effects on asthma severity. Among the domains, pulmonary physiology and rhinitis severity had the largest significant standardized total effects on asthma severity (-0.51 and 0.48, respectively), followed by ETS exposure (0.30) and allergic inflammation (0.22). Although vitamin D had modest but significant indirect effects on asthma severity, its total effect was insignificant (0.01). Conclusions: The standardized effect sizes generated by a causal network analysis quantify the relative contributions of different domains and can be used to prioritize interventions to address asthma severity. C1 [Liu, Andrew H.] Natl Jewish Hlth, Denver, CO USA. [Liu, Andrew H.] Childrens Hosp Colorado, 13123 East 16th Ave,Box B395, Aurora, CO 80045 USA. [Liu, Andrew H.] Univ Colorado, Sch Med, Aurora, CO USA. [Babineau, Denise C.; Krouse, Rebecca Z.; Visness, Cynthia M.] Rho Fed Syst Div, Chapel Hill, NC USA. [Zoratti, Edward M.] Henry Ford Hlth Syst, Detroit, MI USA. [Pongracic, Jacqueline A.; Makhija, Melanie] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. [O'Connor, George T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Wood, Robert A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Hershey, Gurjit K. Khurana; Kercsmar, Carolyn M.] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Gruchalla, Rebecca S.] Univ Texas Southwestern Med Ctr Dallas, Dallas, TX 75390 USA. [Kattan, Meyer; Lamm, Carin I.] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Teach, Stephen J.; Pillai, Dinesh] Childrens Natl Hlth Syst, Washington, DC USA. [Teach, Stephen J.; Pillai, Dinesh] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA. [Gern, James E.; Busse, William W.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Sigelman, Steven M.; Gergen, Peter J.; Togias, Alkis] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Liu, AH (reprint author), Childrens Hosp Colorado, 13123 East 16th Ave,Box B395, Aurora, CO 80045 USA. EM Andrew.liu@childrenscolorado.org FU National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services [HHSN272200900052C, HHSN272201000052I, 1UM1AI114271-01]; National Center for Research Resources (NCRR); National Center for Advancing Translational Sciences (NCATS), NIH [NCRR/NIH UL1TR000451, UL1RR025780, UL1TR000075, NCATS/NIH UL1TR000154, UL1TR001082, UL1TR000077-04, UL1TR000040, UL1TR000150, UL1TR001105] FX This project has been funded in whole or in part with federal funds from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Department of Health and Human Services (under contract nos. HHSN272200900052C and HHSN272201000052I, and 1UM1AI114271-01). Additional support was provided by the National Center for Research Resources (NCRR), and the National Center for Advancing Translational Sciences (NCATS), NIH (under grant nos. NCRR/NIH UL1TR000451, UL1RR025780, UL1TR000075 and NCATS/NIH UL1TR000154, UL1TR001082, UL1TR000077-04, UL1TR000040, UL1TR000150, and UL1TR001105). GlaxoSmithKline (GSK) provided Ventolin, Flovent, Advair, and Flonase under a clinical trial agreement with NIH NIAID; GSK did not have a role in the development or approval of the protocol, conduct of the trial, data analysis, manuscript preparation, or the decision to submit the manuscript for publication. NR 34 TC 2 Z9 2 U1 8 U2 8 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 OCT PY 2016 VL 138 IS 4 BP 1042 EP 1050 DI 10.1016/j.jaci.2016.06.060 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA DZ0AP UT WOS:000385499400009 PM 27720018 ER PT J AU Feeney, M Du Toit, G Roberts, G Sayre, PH Lawson, K Bahnson, HT Sever, ML Radulovic, S Plaut, M Lack, G AF Feeney, Mary Du Toit, George Roberts, Graham Sayre, Peter H. Lawson, Kaitie Bahnson, Henry T. Sever, Michelle L. Radulovic, Suzana Plaut, Marshall Lack, Gideon CA Immune Tolerance Network Leap Stu TI Impact of peanut consumption in the LEAP Study: Feasibility, growth, and nutrition SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Food allergy; allergy prevention; peanut; infant feeding; breast-feeding; nutrition; growth; prospective food diary; protein homeostasis ID HIGH-RISK INFANTS; CONSENSUS COMMUNICATION; ALLERGY; CHILDREN; ADOLESCENTS; PREVENTION; PREVALENCE; ACCEPTANCE; CHILDHOOD; FRUIT AB Background: Early introduction of peanut is an effective strategy to prevent peanut allergy in high-risk infants; however, feasibility and effects on growth and nutritional intake are unknown. Objective: We sought to evaluate the feasibility of introducing peanut in infancy and explore effects on growth and nutritional intake up to age 60 months. Methods: In the Learning Early About Peanut Allergy trial, 640 atopic infants aged 4 to 11 months were randomly assigned to consume (6 g peanut protein per week) or avoid peanut until age 60 months. Peanut consumption and early feeding practices were assessed by questionnaire. Dietary intake was evaluated with prospective food diaries. Anthropometric measurements were taken at all study visits. Results: Peanut was successfully introduced and consumed until 60 months, with median peanut protein intake of 7.5 g/wk (interquartile range, 6.0-9.0 g/wk) in the consumption group compared with 0 g in the avoidance group. Introduction of peanut in breast-feeding infants did not affect the duration of breast-feeding. There were no differences in anthropometric measurements or energy intakes between groups at any visits. Regular peanut consumption led to differences in dietary intakes. Consumers had higher intakes of fat and avoiders had higher carbohydrate intakes; differences were greatest at the upper quartiles of peanut consumption. Protein intakes remained consistent between groups. Conclusions: Introduction of peanut proved feasible in infants at high risk of peanut allergy and did not affect the duration of breast-feeding nor impact negatively on growth or nutrition. Energy balance was achieved in both groups through variations in intakes from fat and carbohydrate while protein homeostasis was maintained. C1 [Feeney, Mary; Du Toit, George; Radulovic, Suzana; Lack, Gideon] Kings Coll London, Dept Pediat Allergy, Div Asthma Allergy & Lung Biol, London, England. [Feeney, Mary; Du Toit, George; Roberts, Graham; Radulovic, Suzana; Lack, Gideon] Guys & St Thomas NHS Fdn Trust, London, England. [Roberts, Graham] Univ Southampton, Southampton, Hants, England. [Roberts, Graham] Natl Inst Hlth, Res Resp Biomed Res Unit, Southampton, Hants, England. [Roberts, Graham] David Hide Ctr, Isle Of Wight, England. [Sayre, Peter H.] Immune Tolerance Network, San Francisco, CA USA. [Sayre, Peter H.] Univ Calif San Francisco, Dept Med, Div Hematol Oncol, San Francisco, CA USA. [Lawson, Kaitie; Bahnson, Henry T.; Sever, Michelle L.] Rho Fed Syst Div, Chapel Hill, NC USA. [Plaut, Marshall] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Lack, G (reprint author), Guys & St Thomas NHS Fdn Trust, Childrens Allergy Unit, 2nd Fl,South Wing,Westminster Bridge Rd, London SE1 7EH, England. EM gideon.lack@kcl.ac.uk FU National Institute of Allergy and Infectious Diseases [UM1AI109565, NO1-AI-15416, HHSN272200800029C]; National Institute of Allergy and Infectious Diseases of the National Institutes of Health; Food Allergy Research & Education (FARE), McLean, Virginia; Medical Research Council & Asthma UK Centre; UK Department of Health through the National Institute for Health Research comprehensive Biomedical Research Centre award; King's College London; King's College Hospital NHS Foundation Trust; National Peanut Board, Atlanta, Georgia; UK Food Standards Agency FX This study was funded by the National Institute of Allergy and Infectious Diseases (award nos. UM1AI109565, NO1-AI-15416, and HHSN272200800029C) and others. This research was performed as a project of the Immune Tolerance Network, an international clinical research consortium headquartered at the Benaroya Research Institute and supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support came from Food Allergy Research & Education (FARE), McLean, Virginia; the Medical Research Council & Asthma UK Centre; the UK Department of Health through the National Institute for Health Research comprehensive Biomedical Research Centre award to Guy's & St Thomas' National Health Service (NHS) Foundation Trust, in partnership with King's College London and King's College Hospital NHS Foundation Trust. The clinical trials unit is supported by the National Peanut Board, Atlanta, Georgia. The UK Food Standards Agency provided additional support for the costs of phlebotomy. NR 41 TC 9 Z9 9 U1 5 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 OCT PY 2016 VL 138 IS 4 BP 1108 EP 1118 DI 10.1016/j.jaci.2016.04.016 PG 11 WC Allergy; Immunology SC Allergy; Immunology GA DZ0AP UT WOS:000385499400016 PM 27297994 ER PT J AU Koplin, JJ Peters, RL Dharmage, SC Gurrin, L Tang, MLK Ponsonby, AL Matheson, M Togias, A Lack, G Allen, KJ AF Koplin, Jennifer J. Peters, Rachel L. Dharmage, Shyamali C. Gurrin, Lyle Tang, Mimi L. K. Ponsonby, Anne-Louise Matheson, Melanie Togias, Alkis Lack, Gideon Allen, Katrina J. CA HealthNuts Study Investigators TI Understanding the feasibility and implications of implementing early peanut introduction for prevention of peanut allergy SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Peanut allergy; infant feeding; guidelines; skin prick test; specific IgE; prevention ID FOOD ALLERGY; EARLY CONSUMPTION; PREVALENCE; INFANTS; HEALTHNUTS; PREDICTORS; DIAGNOSIS; CRITERIA; COHORT; TIME AB Background: A recent randomized trial (the Learning Early About Peanut Allergy [LEAP] study) provided evidence that earlier dietary peanut introduction reduces peanut allergy prevalence in high-risk infants. However, questions remain as to how to identify and target the "at-risk'' population to facilitate timely introduction of peanut. Objective: We sought to use population-based infant peanut allergy data to understand feasibility and implications of implementing the LEAP trial intervention. Methods: Using the HealthNuts study cohort (n = 5276) of 1-year-old infants, we explored the impact of using various criteria to identify infants at high risk of developing peanut allergy, and the implications of skin prick test (SPT) screening before peanut introduction. Results: Screening all infants with early onset eczema and/or egg allergy could require testing 16% of the population and would still miss 23% of peanut allergy cases; 29% of screened infants would require clinical follow-up because of being SPT-positive. Around 11% of high-risk infants were excluded from the LEAP study because of an SPT wheal size of more than 4 mm to peanut at baseline; data from the HealthNuts study suggest that 80% of these would be peanut allergic on food challenge. There were no life-threatening events among either low-or high-risk infants whose parents chose to introduce peanut at home in the first year of life, or in 150 peanut-allergic infants during hospital-based challenges. Conclusions: Based on this large epidemiological study, a population program aiming to identify and screen all infants at risk of peanut allergy would pose major cost and logistic challenges that need to be carefully considered. Further research might be required to provide data for low-risk infants. C1 [Koplin, Jennifer J.; Peters, Rachel L.; Tang, Mimi L. K.; Ponsonby, Anne-Louise; Allen, Katrina J.] Univ Melbourne, Dept Paediat, Murdoch Childrens Res Inst, Parkville, Vic, Australia. [Koplin, Jennifer J.; Peters, Rachel L.; Tang, Mimi L. K.; Ponsonby, Anne-Louise; Allen, Katrina J.] Royal Childrens Hosp, Dept Allergy & Clin Immunol, Parkville, Vic, Australia. [Koplin, Jennifer J.; Dharmage, Shyamali C.; Gurrin, Lyle; Matheson, Melanie] Univ Melbourne, Sch Populat & Global Hlth, Parkville, Vic, Australia. [Togias, Alkis] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Lack, Gideon] Kings Coll London, Dept Pediat Allergy, Div Asthma Allergy & Lung Biol, London, England. [Lack, Gideon] Guys & St Thomas Natl Hlth Serv Fdn Trust, London, England. [Allen, Katrina J.] Univ Manchester, Sch Inflammat & Repair, Manchester, Lancs, England. RP Allen, KJ (reprint author), Royal Childrens Hosp, Murdoch Childrens Res Inst, Flemington Rd, Parkville, Vic 3052, Australia. EM katie.allen@rch.org.au RI Matheson, Melanie/O-4721-2015; OI Matheson, Melanie/0000-0002-5822-3499; Peters, Rachel/0000-0002-2411-6628; Allen, Katrina/0000-0002-1921-4493 FU National Health & Medical Research Council (NHMRC) of Australia; Australian Food Allergy Foundation; Anaphylaxi-Stop; Victorian Government's Operational Infrastructure Support Program FX This work was supported by funding from the National Health & Medical Research Council (NHMRC) of Australia, Australian Food Allergy Foundation, Anaphylaxi-Stop, and the Victorian Government's Operational Infrastructure Support Program. The study sponsors had no involvement in the study design, collection, analysis, and interpretation of data, writing of the report, or decision to submit the article for publication. NR 19 TC 7 Z9 7 U1 3 U2 3 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 OCT PY 2016 VL 138 IS 4 BP 1131 EP + DI 10.1016/j.jaci.2016.04.011 PG 13 WC Allergy; Immunology SC Allergy; Immunology GA DZ0AP UT WOS:000385499400019 PM 27260320 ER PT J AU Chandrasekaran, P Zimmerman, O Paulson, M Sampaio, EP Freeman, AF Sowerwine, KJ Hurt, D Alcantara-Montiel, JC Hsu, AP Holland, SM AF Chandrasekaran, Prabha Zimmerman, Ofer Paulson, Michelle Sampaio, Elizabeth P. Freeman, Alexandra F. Sowerwine, Kathryn J. Hurt, Darell Alcantara-Montiel, Julio C. Hsu, Amy P. Holland, Steven M. TI Distinct mutations at the same positions of STAT3 cause either loss or gain of function SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID GRANULAR LYMPHOCYTIC-LEUKEMIA; HYPER-IGE SYNDROME C1 [Chandrasekaran, Prabha; Zimmerman, Ofer; Paulson, Michelle; Sampaio, Elizabeth P.; Freeman, Alexandra F.; Sowerwine, Kathryn J.; Hsu, Amy P.; Holland, Steven M.] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Chandrasekaran, Prabha] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. [Hurt, Darell] NIAID, Bioinformat & Computat Biosci Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Alcantara-Montiel, Julio C.] CINVES TAV IPN, Dept Mol Biomed, Mexico City, DF, Mexico. RP Holland, SM (reprint author), NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM smh@nih.gov FU CCR NIH HHS [HHSN261200800001C]; Intramural NIH HHS [Z01 AI000646-16]; NCI NIH HHS [HHSN261200800001E] NR 13 TC 1 Z9 1 U1 1 U2 1 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 OCT PY 2016 VL 138 IS 4 BP 1222 EP 1224 DI 10.1016/j.jaci.2016.05.007 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA DZ0AP UT WOS:000385499400037 PM 27345172 ER PT J AU Weeks, J Briggs, JP AF Weeks, John Briggs, Josephine P. TI The New USA NIH Strategic Plan for Complementary and Integrative Health: Interview with Josephine Briggs, MD: Director, National Center for Complementary and Integrative Health (Part 2) SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Editorial Material C1 [Briggs, Josephine P.] NIH, NCCIH, USA Natl Inst Hlth NIH, Bldg 10, Bethesda, MD 20892 USA. [Briggs, Josephine P.] NIH, Precis Med Initiat, Cohort Program, Bldg 10, Bethesda, MD 20892 USA. [Briggs, Josephine P.] NIH, Common Fund Hlth Care Syst Res Collaboratory, Bldg 10, Bethesda, MD 20892 USA. [Briggs, Josephine P.] NIH, Steering Comm, Bldg 10, Bethesda, MD 20892 USA. [Briggs, Josephine P.] NIH, Sci Management Review Board, Bldg 10, Bethesda, MD 20892 USA. [Briggs, Josephine P.] NIH, Pain Consortium, Bldg 10, Bethesda, MD 20892 USA. [Briggs, Josephine P.] Univ Munich, Inst Physiol, Munich, Germany. [Briggs, Josephine P.] Univ Michigan, Internal Med & Physiol, Ann Arbor, MI 48109 USA. [Briggs, Josephine P.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. [Briggs, Josephine P.] NIH, Div Kidney Urol & Hematol Dis, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 EI 1557-7708 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD OCT PY 2016 VL 22 IS 10 BP 765 EP 767 DI 10.1089/acm.2016.29011.jjw PG 3 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA DZ5SU UT WOS:000385922600002 PM 27653499 ER PT J AU Scott, JM Robinson, SE Holroyd, T Coppola, R Sato, S Inati, SK AF Scott, Jonathan M. Robinson, Stephen E. Holroyd, Tom Coppola, Richard Sato, Susumu Inati, Sara K. TI Localization of Interictal Epileptic Spikes With MEG: Optimization of an Automated Beamformer Screening Method (SAMepi) in a Diverse Epilepsy Population SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Magnetoencephalography; Source localization; Epilepsy; Beamforming; Kurtosis ID INTRACRANIAL EEG; MAGNETOENCEPHALOGRAPHY AB Purpose: To describe and optimize an automated beamforming technique followed by identification of locations with excess kurtosis (g2) for efficient detection and localization of interictal spikes in patients with medically refractory epilepsy. Methods: Synthetic aperture magnetometry with g2 averaged over a sliding time window (SAMepi) was performed in seven patients with focal epilepsy and five healthy volunteers. The effect of varied window lengths on detection of spiking activity was evaluated. Results: Sliding window lengths of 0.5 to 10 seconds performed similarly, with 0.5- and 1-second windows detecting spiking activity in 1 of the 3 virtual sensor locations with highest kurtosis. These locations were concordant with the region of eventual surgical resection in these seven patients who remained seizure-free at 1 year. Average g2 values increased with increasing sliding window length in all subjects. In healthy volunteers, kurtosis values stabilized in data sets longer than 2 minutes. Conclusions: SAMepi using g2 averaged over 1-second sliding time windows in data sets of at least 2 minutes of duration reliably identified interictal spiking and the presumed seizure focus in these seven patients. Screening the five locations with highest kurtosis values for spiking activity is an efficient and accurate technique for localizing interictal activity using magnetoencephalography. Significance: SAMepi should be applied using the parameter values and procedure described for optimal detection and localization of interictal spikes. Use of this screening procedure could significantly improve the efficiency of magnetoencephalography analysis if clinically validated. C1 [Scott, Jonathan M.; Sato, Susumu; Inati, Sara K.] NINDS, EEG Sect, NIH, 10 CRC,Room 7-3753,10 Ctr Dr,MSC 1404, Bethesda, MD 20892 USA. [Robinson, Stephen E.; Holroyd, Tom; Coppola, Richard] NIMH, MEG Core Facil, NIH, Bethesda, MD 20892 USA. RP Scott, JM (reprint author), NINDS, EEG Sect, NIH, 10 CRC,Room 7-3753,10 Ctr Dr,MSC 1404, Bethesda, MD 20892 USA. EM jonathan.m.scott2013@gmail.com FU Intramural Research Program of the National Institutes of Health, National Institute of Neurological Disorders and Stroke (NINDS) FX Supported by the Intramural Research Program of the National Institutes of Health, National Institute of Neurological Disorders and Stroke (NINDS). NR 18 TC 0 Z9 0 U1 4 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0736-0258 EI 1537-1603 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD OCT PY 2016 VL 33 IS 5 BP 414 EP 420 DI 10.1097/WNP.0000000000000255 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DZ2HP UT WOS:000385663200007 PM 27760068 ER PT J AU Clark, C Thomas, D Mejzner, N Llewellyn, D Ferrucci, L Campbell, J AF Clark, Christopher Thomas, Daniel Mejzner, Natasha Llewellyn, David Ferrucci, Luigi Campbell, John TI Can we predict who should be tested for postural hypotension? Derivation and validation of a prediction tool SO JOURNAL OF HUMAN HYPERTENSION LA English DT Meeting Abstract C1 [Clark, Christopher; Thomas, Daniel; Mejzner, Natasha; Llewellyn, David; Campbell, John] Univ Exeter, Sch Med, Exeter EX4 4QJ, Devon, England. [Ferrucci, Luigi] NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9240 EI 1476-5527 J9 J HUM HYPERTENS JI J. Hum. Hypertens. PD OCT PY 2016 VL 30 IS 10 SI SI MA O-15 BP 640 EP 640 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DZ3ZY UT WOS:000385797000025 ER PT J AU Murphy, J Mark, H AF Murphy, Jeanne Mark, Hayley TI Self-Sampling as an Intervention to Promote Cervical Cancer Screening Among Women With HIV SO JOURNAL OF LOWER GENITAL TRACT DISEASE LA English DT Letter C1 [Murphy, Jeanne] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Rockville, MD 20850 USA. [Mark, Hayley] Towson Univ, Dept Nursing, Towson, MD USA. RP Murphy, J (reprint author), NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Rockville, MD 20850 USA. EM jeanne.murphy@nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 2 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 1089-2591 EI 1526-0976 J9 J LOW GENIT TRACT DI JI J. Low. Genit. Tract. Dis. PD OCT PY 2016 VL 20 IS 4 BP e63 EP e63 DI 10.1097/LGT.0000000000000259 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DY8II UT WOS:000385372600006 PM 27556424 ER PT J AU Kim, H Sanchez, GAM Goldbach-Mansky, R AF Kim, Hanna Sanchez, Gina A. Montealegre Goldbach-Mansky, Raphaela TI Insights from Mendelian Interferonopathies: Comparison of CANDLE, SAVI with AGS, Monogenic Lupus SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE Type I IFN; Autoinflammatory; Autoimmune; Candle; SAVI; Interferonopathies ID AICARDI-GOUTIERES-SYNDROME; FAMILIAL CHILBLAIN LUPUS; ATYPICAL NEUTROPHILIC DERMATOSIS; INNATE IMMUNE-RESPONSE; SINGLETON-MERTEN SYNDROME; NAKAJO-NISHIMURA SYNDROME; OF-FUNCTION MUTATION; MEDIATED CELL-DEATH; I INTERFERON; EXTRACELLULAR TRAPS AB Autoinflammatory disorders are sterile inflammatory conditions characterized by episodes of early-onset fever and disease-specific patterns of organ inflammation. Recently, the discoveries of monogenic disorders with strong type I interferon (IFN) signatures caused by mutations in proteasome degradation and cytoplasmic RNA and DNA sensing pathways suggest a pathogenic role of IFNs in causing autoinflammatory phenotypes. The IFN response gene signature (IGS) has been associated with systemic lupus erythematosus (SLE) and other autoimmune diseases. In this review, we compare the clinical presentations and pathogenesis of two IFN-mediated autoinflammatory diseases, CANDLE and SAVI, with Aicardi GoutiSres syndrome (AGS) and monogenic forms of SLE (monoSLE) caused by loss-of-function mutations in complement 1 (C1q) or the DNA nucleases, DNASE1 and DNASE1L3. We outline differences in intracellular signaling pathways that fuel a pathologic type I IFN amplification cycle. While IFN amplification is caused by predominantly innate immune cell dysfunction in SAVI, CANDLE, and AGS, autoantibodies to modified RNA and DNA antigens interact with tissues and immune cells including neutrophils and contribute to IFN upregulation in some SLE patients including monoSLE, thus justifying a grouping of "autoinflammatory" and "autoimmune" interferonopathies. Understanding of the differences in the cellular sources and signaling pathways will guide new drug development and the use of emerging targeted therapies. C1 [Kim, Hanna] NIAMSD, Translat Res, Pediat Translat Res Branch, NIH, Bethesda, MD 20892 USA. [Sanchez, Gina A. Montealegre; Goldbach-Mansky, Raphaela] NIAID, Translat Autoinflammatory Dis Studies, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Sanchez, Gina A. Montealegre; Goldbach-Mansky, Raphaela] NIAMS, NIH, Bethesda, MD USA. RP Kim, H (reprint author), NIAMSD, Translat Res, Pediat Translat Res Branch, NIH, Bethesda, MD 20892 USA.; Goldbach-Mansky, R (reprint author), NIAID, Translat Autoinflammatory Dis Studies, 9000 Rockville Pike, Bethesda, MD 20892 USA.; Goldbach-Mansky, R (reprint author), NIAMS, NIH, Bethesda, MD USA. EM hanna.kim@nih.gov; gina.montealegre@nih.gov; goldbacr@mail.nih.gov OI Kim, Hanna/0000-0002-0595-6533 FU Intramural Research Program of the NIH; NIAID; NIAMS FX This research was supported by the Intramural Research Program of the NIH, NIAID, and NIAMS. The authors would like to thank Dr. Ann Marschuk-Rothstein and Dr. Adriana Almeida de Jesus for helpful discussions. NR 120 TC 1 Z9 1 U1 4 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0946-2716 EI 1432-1440 J9 J MOL MED JI J. Mol. Med. PD OCT PY 2016 VL 94 IS 10 BP 1111 EP 1127 DI 10.1007/s00109-016-1465-5 PG 17 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA DY6PP UT WOS:000385250200005 PM 27678529 ER PT J AU Akgul, G McBain, CJ AF Akguel, Guelcan McBain, Chris J. TI Diverse roles for ionotropic glutamate receptors on inhibitory interneurons in developing and adult brain SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Review ID CA2+-PERMEABLE AMPA RECEPTORS; RAT HIPPOCAMPAL-NEURONS; PARVALBUMIN-EXPRESSING INTERNEURONS; LACUNOSUM MOLECULARE INTERNEURONS; DUAL INTRACELLULAR-RECORDINGS; PRESYNAPTIC NMDA RECEPTORS; CALCIUM-PERMEABLE AMPA; LONG-TERM POTENTIATION; SUBUNIT MESSENGER-RNAS; KAINATE RECEPTORS AB Glutamate receptor-mediated recruitment of GABAergic inhibitory interneurons is a critical determinant of network processing. Early studies observed that many, but not all, interneuron glutamatergic synapses contain AMPA receptors that are GluA2-subunit lacking and Ca2+ permeable, making them distinct from AMPA receptors at most principal cell synapses. Subsequent studies demonstrated considerable alignment of synaptic AMPA and NMDA receptor subunit composition within specific subtypes of interneurons, suggesting that both receptor expression profiles are developmentally and functionally linked. Indeed glutamate receptor expression profiles are largely predicted by the embryonic origins of cortical interneurons within the medial and caudal ganglionic eminences of the developing telencephalon. Distinct complements of AMPA and NMDA receptors within different interneuron subpopulations contribute to the differential recruitment of functionally divergent interneuron subtypes by common afferent inputs for appropriate feed-forward and feedback inhibitory drive and network entrainment. In contrast, the lesser-studied kainate receptors, which are often present at both pre- and postsynaptic sites, appear to follow an independent developmental expression profile. Loss of specific ionotropic glutamate receptor (iGluR) subunits during interneuron development has dramatic consequences for both cellular and network function, often precipitating circuit inhibition-excitation imbalances and in some cases lethality. Here we briefly review recent findings highlighting the roles of iGluRs in interneuron development. C1 [Akguel, Guelcan; McBain, Chris J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Porter Neurosci Res Ctr, Rm3C903,Lincoln Dr, Bethesda, MD 20892 USA. RP McBain, CJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. EM mcbainc@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [Z1A-HD001205-21] FX This work was funded by an Intramural research award from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Z1A-HD001205-21). NR 137 TC 2 Z9 2 U1 5 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3751 EI 1469-7793 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD OCT 1 PY 2016 VL 594 IS 19 BP 5471 EP 5490 DI 10.1113/JP271764 PG 20 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA DY8DK UT WOS:000385358500011 PM 26918438 ER PT J AU Lawrence, E Fry, RJ AF Lawrence, Emily Fry, Richard J. TI Content Blocking and the Patron as Situated Knower: What Would It Take for an Internet Filter to Work? SO LIBRARY QUARTERLY LA English DT Article ID INTELLECTUAL FREEDOM; LIBRARIES AB Librarians often object to Internet filters on the grounds that filters are prone to overblocking and underblocking. This argument implies that a significant problem with contemporary filters is that they are insufficiently fine-grained. In this article, we posit that present-day filters will always be conceptually capable of failure, regardless of how granular their content analysis becomes. This is because, we argue, objections to content are best understood as objections to problematic interactions between content and particular knowers. We import the concept of the situated knower from feminist epistemology to capture the heterogeneous, socially embedded nature of patrons, about whom we cannot make blunt generalizations for filtering purposes. A successful filter would need information about these differently situated patrons, the content they seek, and the interactions between the two. We conclude that a genuinely successful Internet filter would therefore need to be both mind reading and fortune-telling. C1 [Lawrence, Emily] Univ Illinois, Grad Sch Lib & Informat Sci, Champaign, IL 61801 USA. [Lawrence, Emily] Natl Lib Med, Reference Serv, Bethesda, MD 20894 USA. [Lawrence, Emily] Natl Lib Med, Web Serv, Bethesda, MD 20894 USA. [Fry, Richard J.] Southern Illinois Univ, Edwardsville, IL USA. RP Lawrence, E (reprint author), Univ Illinois, Grad Sch Lib & Informat Sci, Champaign, IL 61801 USA.; Lawrence, E (reprint author), Natl Lib Med, Reference Serv, Bethesda, MD 20894 USA.; Lawrence, E (reprint author), Natl Lib Med, Web Serv, Bethesda, MD 20894 USA. EM elawrnc2@illinois.edu; rfry@siue.edu NR 38 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0024-2519 EI 1549-652X J9 LIBR QUART JI Libr. Q. PD OCT PY 2016 VL 86 IS 4 BP 403 EP 418 DI 10.1086/688030 PG 16 WC Information Science & Library Science SC Information Science & Library Science GA DZ2EU UT WOS:000385655900003 ER PT J AU Park, YMM Fung, TT Steck, SE Zhang, JJ Hazlett, LJ Han, K Lee, SH Merchant, AT AF Park, Yong-Moon Mark Fung, Teresa T. Steck, Susan E. Zhang, Jiajia Hazlett, Linda J. Han, Kyungdo Lee, Seung-Hwan Merchant, Anwar T. TI Diet Quality and Mortality Risk in Metabolically Obese Normal-Weight Adults SO MAYO CLINIC PROCEEDINGS LA English DT Article ID HEALTHY EATING INDEX; NONDIABETIC KOREAN POPULATION; GUIDELINES-FOR-AMERICANS; HYPERTENSION DASH DIET; MAJOR CHRONIC DISEASE; C-REACTIVE PROTEIN; BODY-MASS INDEX; CARDIOVASCULAR-DISEASE; WAIST CIRCUMFERENCE; NATIONAL-HEALTH AB Objective: To examine the associations among the Dietary Approaches to Stop Hypertension (DASH)-style diet, the Healthy Eating Index (HEI), and mortality risk in metabolically obese normal-weight (MONW) adults. Patients and Methods: Data were from normal-weight (body mass index of 18.5 to < 25) adults aged 30 to 90 years at baseline in the Third National Health and Nutrition Examination Survey, October 18, 1988, through October 15, 1994, followed up for deaths (all-cause, cardiovascular, and cancer related) until December 31, 2011. A total of 2103 participants without known cardiovascular disease and cancer at baseline were included in this prospective cohort study. Metabolic obesity was defined as having 2 or more of the following: high glucose, blood pressure, triglyceride, C-reactive protein, and insulin resistance values and low high-density lipoprotein cholesterol levels; metabolic healthy status was defined as having 0 or 1 of these metabolic derangements. Results: During median follow-up of 18.6 years, there were 344 and 296 deaths in the MONW and metabolically healthy normal-weight (MHNW) phenotypes, respectively. In MONW individuals, a 1-SD increment in adherence to a DASH diet (2 points) or HEI (14 points) was significantly associated with reductions (17% [hazard ratio (HR), 0.83; 95% CI, 0.72-0.97] and 22% [HR, 0.78; 95% CI, 0.68-0.90], respectively) in the risk of all-cause mortality, after adjustment for potential confounders. The corresponding HRs for cardiovascular disease mortality were 0.72 (95% CI, 0.55-0.94) and 0.79 (95% CI, 0.65-0.97), respectively. In addition, reduction of cancer mortality was observed with 1-SD increment of HEI (HR, 0.63; 95% CI, 0.46-0.88). However, no association was observed in the MHNW phenotype. Sensitivity analyses suggested relationships robust to different definitions of MONW and also dose responses with the number of metabolic derangements. Conclusion: Higher diet quality scores were associated with lower risk of mortality in normal-weight individuals with metabolic abnormalities. (C) 2016 Mayo Foundation for Medical Education and Research C1 [Park, Yong-Moon Mark; Steck, Susan E.; Zhang, Jiajia; Hazlett, Linda J.; Merchant, Anwar T.] Univ South Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, 915 Greene St, Columbia, SC 29208 USA. [Park, Yong-Moon Mark] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. [Fung, Teresa T.] Simmons Coll, Dept Nutr, Boston, MA 02115 USA. [Fung, Teresa T.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Han, Kyungdo] Catholic Univ Korea, Coll Med, Dept Biostat, Seoul, South Korea. [Lee, Seung-Hwan] Catholic Univ Korea, Coll Med, Dept Internal Med, Div Endocrinol & Metab, Seoul, South Korea. RP Merchant, AT (reprint author), Univ South Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, 915 Greene St, Columbia, SC 29208 USA. EM merchant@mailbox.sc.edu OI Lee, Seung-Hwan/0000-0002-3964-3877; PARK, YONG-MOON/0000-0002-5879-6879 NR 50 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD OCT PY 2016 VL 91 IS 10 BP 1372 EP 1383 DI 10.1016/j.mayocp.2016.06.022 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA DZ6AQ UT WOS:000385944400011 PM 27712636 ER PT J AU Maio, N Rouault, TA AF Maio, N. Rouault, T. A. TI Mammalian Fe-S proteins: definition of a consensus motif recognized by the co-chaperone HSC20 SO METALLOMICS LA English DT Review ID IRON-SULFUR CLUSTER; MITOCHONDRIAL CYSTEINE DESULFURASE; RESONANCE EPR SPECTROSCOPY; ASSEMBLY SCAFFOLD PROTEIN; X-RAY-STRUCTURE; ESCHERICHIA-COLI; COMPLEX-I; SACCHAROMYCES-CEREVISIAE; ADENOSYLMETHIONINE ENZYMES; AZOTOBACTER-VINELANDII AB Iron-sulfur (Fe-S) clusters are inorganic cofactors that are fundamental to several biological processes in all three kingdoms of life. In most organisms, Fe-S clusters are initially assembled on a scaffold protein, ISCU, and subsequently transferred to target proteins or to intermediate carriers by a dedicated chaperone/co-chaperone system. The delivery of assembled Fe-S clusters to recipient proteins is a crucial step in the biogenesis of Fe-S proteins, and, in mammals, it relies on the activity of a multiprotein transfer complex that contains the chaperone HSPA9, the co-chaperone HSC20 and the scaffold ISCU. How the transfer complex efficiently engages recipient Fe-S target proteins involves specific protein interactions that are not fully understood. This mini review focuses on recent insights into the molecular mechanism of amino acid motif recognition and discrimination by the co-chaperone HSC20, which guides Fe-S cluster delivery. C1 [Maio, N.; Rouault, T. A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Mol Med, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Rouault, TA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Mol Med, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rouault@mail.nih.gov FU intramural program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD FX This work was supported by the intramural program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD. NR 163 TC 0 Z9 0 U1 8 U2 8 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1756-5901 EI 1756-591X J9 METALLOMICS JI Metallomics PD OCT 1 PY 2016 VL 8 IS 10 BP 1032 EP 1046 DI 10.1039/c6mt00167j PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DZ1JF UT WOS:000385594000001 PM 27714045 ER PT J AU Yi, MN Yu, PP Lu, Q Geller, HM Yu, ZH Chen, HZ AF Yi, Mengni Yu, Panpan Lu, Qin Geller, Herbert M. Yu, Zhihua Chen, Hongzhuan TI KCa3.1 constitutes a pharmacological target for astrogliosis associated with Alzheimer's disease SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article DE Astrogliosis; Alzheimer's disease; GFAP; Mouse; Culture ID ACCELERATED MOUSE SAMP8; K+ CHANNEL; REACTIVE ASTROCYTES; THERAPEUTIC TARGET; UP-REGULATION; IN-VIVO; INHIBITION; CALCIUM; MODEL; MEMORY AB Alzheimer's disease (AD) is the most common type of dementia and is characterized by a progression from decline of episodic memory to a global impairment of cognitive function. Astrogliosis is a hallmark feature of AD, and reactive gliosis has been considered as an important target for intervention in various neurological disorders. We previously found in astrocyte cultures that the expression of the intermediate conductance calcium-activated potassium channel KCa3.1 was increased in reactive astrocytes induced by TGF-beta, while pharmacological blockade or genetic deletion of KCa3.1 attenuated astrogliosis. In this study, we sought to suppress reactive gliosis in the context of AD by inhibiting KCa3.1 and evaluate its effects on the cognitive impairment using murine animal models such as the senescence-accelerated mouse prone 8 (SAMP8) model that exhibits some AD-like symptoms. We found KCa3.1 expression was increased in reactive astrocytes as well as neurons in the brains of both SAMP8 mice and Alzheimer's disease patients. Blockade of KCa3.1 with the selective inhibitor TRAM-34 in SAMP8 mice resulted in a decrease in astrogliosis as well as microglia activation, and moreover an attenuation of memory deficits. Using KCa3.1 knockout mice, we further confirmed that deletion of KCa3.1 reduced the activation of astrocytes and microglia, and rescued the memory loss induced by intrahippocampal A beta(1-42) peptide injection. We also found in astrocyte cultures that blockade of KCa3.1 or deletion of KCa3.1 suppressed A beta oligomer-induced astrogliosis. Our data suggest that KCa3.1 inhibition might represent a promising therapeutic strategy for AD treatment. (C) 2016 Elsevier Inc. All rights reserved. C1 [Yi, Mengni; Lu, Qin; Yu, Zhihua; Chen, Hongzhuan] Shanghai Jiao Tong Univ, Sch Med, Inst Med Sci, Dept Pharmacol, 280 South Chongqing Rd, Shanghai 200025, Peoples R China. [Yu, Panpan] Jinan Univ, Guangdong Hongkong Macau Inst CNS Regenerat, Guangzhou 510632, Guangdong, Peoples R China. [Yu, Panpan] Jinan Univ, Minist Educ, Joint Int Res Lab CNS Regenerat, Guangzhou 510632, Guangdong, Peoples R China. [Geller, Herbert M.] NHLBI, Dev Neurobiol Sect, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA. RP Yu, ZH; Chen, HZ (reprint author), Shanghai Jiao Tong Univ, Sch Med, Inst Med Sci, Dept Pharmacol, 280 South Chongqing Rd, Shanghai 200025, Peoples R China. EM yuzhihua@shsmu.edu.cn; hongzhuan_chen@hotmail.com FU Science and Technology Commission of Shanghai Municipality [16ZR1418700]; National Natural Science Foundation of China [81102491]; Natural Science Foundation of Guangdong Province [2016A030313096]; Fundamental Research Funds for the Central Universities [21616340] FX This work was supported by Science and Technology Commission of Shanghai Municipality grant 16ZR1418700, National Natural Science Foundation of China grant 81102491, Natural Science Foundation of Guangdong Province (2016A030313096), the Fundamental Research Funds for the Central Universities (21616340). The authors declare no competing financial interests. NR 48 TC 1 Z9 1 U1 3 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 EI 1095-9327 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD OCT PY 2016 VL 76 BP 21 EP 32 DI 10.1016/j.mcn.2016.08.008 PG 12 WC Neurosciences SC Neurosciences & Neurology GA DY9RA UT WOS:000385471600003 PM 27567685 ER PT J AU Keasey, SL Natesan, M Pugh, C Kamata, T Wuchty, S Ulrich, RG AF Keasey, Sarah L. Natesan, Mohan Pugh, Christine Kamata, Teddy Wuchty, Stefan Ulrich, Robert G. TI Cell-free Determination of Binary Complexes That Comprise Extended Protein-Protein Interaction Networks of Yersinia pestis SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID TANDEM AFFINITY PURIFICATION; RNA CHAPERONE HFQ; ESCHERICHIA-COLI; HELICOBACTER-PYLORI; INTERACTION MAP; III SECRETION; IN-VITRO; PSEUDOTUBERCULOSIS; INHIBITORS; BIOLOGY AB Binary protein interactions form the basic building blocks of molecular networks and dynamic assemblies that control all cellular functions of bacteria. Although these protein interactions are a potential source of targets for the development of new antibiotics, few high-confidence data sets are available for the large proteomes of most pathogenic bacteria. We used a library of recombinant proteins from the plague bacterium Yersinia pestis to probe planar microarrays of immobilized proteins that represented similar to 85% (3552 proteins) of the bacterial proteome, resulting in >77,000 experimentally determined binary interactions. Moderate (K-D similar to mu M) to high-affinity (K-D similar to nM) interactions were characterized for >1600 binary complexes by surface plasmon resonance imaging of microarrayed proteins. Core binary interactions that were in common with other gram-negative bacteria were identified from the results of both microarray methods. Clustering of proteins within the interaction network by function revealed statistically enriched complexes and pathways involved in replication, biosynthesis, virulence, metabolism, and other diverse biological processes. The interaction pathways included many proteins with no previously known function. Further, a large assembly of proteins linked to transcription and translation were contained within highly interconnected subregions of the network. The two-tiered microarray approach used here is an innovative method for detecting binary interactions, and the resulting data will serve as a critical resource for the analysis of protein interaction networks that function within an important human pathogen. C1 [Keasey, Sarah L.; Natesan, Mohan; Pugh, Christine; Kamata, Teddy; Ulrich, Robert G.] US Army Med Res Inst Infect Dis, Mol & Translat Sci Div, Frederick, MD 21702 USA. [Keasey, Sarah L.] Univ Maryland Baltimore Cty, Dept Biol Sci, Baltimore, MD 21250 USA. [Wuchty, Stefan] NIH, Natl Ctr Biotechnol Informat, Bldg 10, Bethesda, MD 20892 USA. [Wuchty, Stefan] Univ Miami, Dept Comp Sci, Coral Gables, FL 33124 USA. RP Ulrich, RG (reprint author), USAMRIID, Mol & Translat Sci, 1425 Porter St, Frederick, MD 21702 USA. EM rulrich@bhsai.org FU Defense Threat Reduction Agency (RGU) FX This work was supported in part by a grant from the Defense Threat Reduction Agency (RGU) and by appointment of SLK to the Research Participation Program for the U.S. Army Medical Research and Materiel Command, administered through an agreement between the U.S. Department of Energy and the USAMRMC. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the U.S. Army or the National Institutes of Health. 10.1074/mcp.M116.059337. NR 51 TC 0 Z9 0 U1 3 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 EI 1535-9484 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2016 VL 15 IS 10 BP 3220 EP 3232 DI 10.1074/mcp.M116.059337 PG 13 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA DY8JB UT WOS:000385374800010 PM 27489291 ER PT J AU Norris, EL Headlam, MJ Dave, KA Smith, DD Bukreyev, A Singh, T Jayakody, BA Chappell, KJ Collins, PL Gorman, JJ AF Norris, Emma L. Headlam, Madeleine J. Dave, Keyur A. Smith, David D. Bukreyev, Alexander Singh, Toshna Jayakody, Buddhika A. Chappell, Keith J. Collins, Peter L. Gorman, Jeffrey J. TI Proteoform-Specific Insights into Cellular Proteome Regulation SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID TRANSFER-RNA-SYNTHETASE; SHOTGUN PROTEOMICS; INTERFERON-GAMMA; MASS-SPECTROMETRY; PEPTIDE IDENTIFICATION; GEL-ELECTROPHORESIS; EPITHELIAL-CELLS; GENE-EXPRESSION; VIRUS; PROTEINS AB Knowledge regarding compositions of proteomes at the proteoform level enhances insights into cellular phenotypes. A strategy is described herein for discovery of proteoform-specific information about cellular proteomes. This strategy involved analysis of data obtained by bottom-up mass spectrometry of multiple protein OGE separations on a fraction by fraction basis. The strategy was exemplified using five matched sets of lysates of uninfected and human respiratory syncytial virus-infected A549 cells. Template matching demonstrated that 67.3% of 10475 protein profiles identified focused to narrow pI windows indicative of efficacious focusing. Furthermore, correlation between experimental and theoretical pI gradients indicated reproducible focusing. Based on these observations a proteoform profiling strategy was developed to identify proteoforms, detect proteoform diversity and discover potential proteoform regulation. One component of this strategy involved examination of the focusing profiles for protein groups. A novel concordance analysis facilitated differentiation between proteoforms, including proteoforms generated by alternate splicing and proteolysis. Evaluation of focusing profiles and concordance analysis were applicable to cells from a single and/or multiple biological states. Statistical analyses identified proteoform variation between biological states. Regulation relevant to cellular responses to human respiratory syncytial virus was revealed. Western blotting and Protomap analyses validated the proteoform regulation. Discovery of STAT1, WARS, MX1, and HSPB1 proteoform regulation by human respiratory syncytial virus highlighted the impact of the profiling strategy. Novel truncated proteoforms of MX1 were identified in infected cells and phosphorylation driven regulation of HSPB1 proteoforms was correlated with infection. The proteoform profiling strategy is generally applicable to investigating interactions between viruses and host cells and the analysis of other biological systems. C1 [Norris, Emma L.; Headlam, Madeleine J.; Dave, Keyur A.; Singh, Toshna; Jayakody, Buddhika A.; Gorman, Jeffrey J.] QIMR Berghofer Med Res Inst, Prot Discovery Ctr, Herston, Qld, Australia. [Smith, David D.] QIMR Berghofer Med Res Inst, Stat Unit, Herston, Qld, Australia. [Bukreyev, Alexander; Collins, Peter L.] NIAID, Resp Virus Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Chappell, Keith J.; Gorman, Jeffrey J.] Univ Queensland, Sch Chem & Mol Biosci, St Lucia, Qld, Australia. [Bukreyev, Alexander] Univ Texas Med Branch, Galveston Natl Lab, Dept Pathol, Keiller Bldg,Room 3-145,301 Univ Blvd, Galveston, TX 77555 USA. [Bukreyev, Alexander] Univ Texas Med Branch, Galveston Natl Lab, Dept Microbiol & Immunol, Keiller Bldg,Room 3-145,301 Univ Blvd, Galveston, TX 77555 USA. RP Gorman, JJ (reprint author), Royal Brisbane Hosp, Prot Discovery Ctr, QIMR Berghofer, Locked Bag 2000, Herston, Qld 4029, Australia. EM jeff.gorman@qimr.edu.au OI Smith, David/0000-0001-9644-2353; Headlam, Madeleine/0000-0001-6812-2459 FU Bioplatforms Australia; Queensland State Government through the Australian Government National Collaborative Infrastructure Strategy (NCRIS); EIF Fund FX Access to proteomic infrastructure in the QIMR Berghofer Protein Discovery Centre was made possible by funding from Bioplatforms Australia and the Queensland State Government provided through the Australian Government National Collaborative Infrastructure Strategy (NCRIS) and EIF Fund. NR 65 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 EI 1535-9484 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD OCT PY 2016 VL 15 IS 10 BP 3297 EP 3320 DI 10.1074/mcp.O116.058438 PG 24 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA DY8JB UT WOS:000385374800016 PM 27451424 ER PT J AU Turkbey, B Choyke, PL AF Turkbey, Baris Choyke, Peter L. TI Birth of a standard: MET-RADS-P for metastatic prostate cancer SO NATURE REVIEWS UROLOGY LA English DT Editorial Material C1 [Turkbey, Baris; Choyke, Peter L.] NCI, Mol Imaging Program, US Natl Inst Hlth, 10 Ctr Dr,Room B3B69, Bethesda, MD 20892 USA. RP Turkbey, B (reprint author), NCI, Mol Imaging Program, US Natl Inst Hlth, 10 Ctr Dr,Room B3B69, Bethesda, MD 20892 USA. EM turkbeyi@mail.nih.gov NR 6 TC 0 Z9 0 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4812 EI 1759-4820 J9 NAT REV UROL JI Nat. Rev. Urol. PD OCT PY 2016 VL 13 IS 10 BP 568 EP 570 DI 10.1038/nrurol.2016.163 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA DY9TH UT WOS:000385477500014 PM 27578044 ER PT J AU Cardenas, SA Kassem, L Brotman, MA Leibenluft, E McMahon, FJ AF Cardenas, Stephanie A. Kassem, Layla Brotman, Melissa A. Leibenluft, Ellen McMahon, Francis J. TI Neurocognitive functioning in euthymic patients with bipolar disorder and unaffected relatives: A review of the literature SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE Bipolar disorder; Neuropsychology; Cognition; At-risk; Relatives; Review ID INCREASED INTRASUBJECT VARIABILITY; TRAUMATIC BRAIN-INJURY; 1ST-DEGREE RELATIVES; I DISORDER; NEUROPSYCHOLOGICAL DEFICITS; COGNITIVE IMPAIRMENT; MULTIGENERATIONAL FAMILIES; SUSTAINED ATTENTION; EXECUTIVE FUNCTIONS; GENETIC LIABILITY AB Background: Neurocognitive deficits are present in bipolar disorder (BD) patients and their unaffected (nonbipolar) relatives, but it is not clear which domains are most often impaired and the extent of the impairment resulting from shared genetic factors. In this literature review, we address these issues and identify specific neurocognitive tasks most sensitive to cognitive deficits in patients and unaffected relatives. Method: We conducted a systematic review in Web of Science, PubMed/Medline and PsycINFO databases. Results: Fifty-one articles assessing cognitive functioning in BD patients (23 studies) and unaffected relatives (28 studies) were examined. Patients and, less so, relatives show impairments in attention, processing speed, verbal learning/memory, and verbal fluency. Conclusion: Studies were more likely to find impairment in patients than relatives, suggesting that some neurocognitive deficits may be a result of the illness itself and/or its treatment. However, small sample sizes, differences among relatives studied (e.g., relatedness, diagnostic status, age), and differences in assessment instruments may contribute to inconsistencies in reported neurocognitive performance among relatives. Additional studies addressing these issues are needed. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Cardenas, Stephanie A.] NIH, 10 Ctr Dr,RM 3D54,MSC 1264, Bethesda, MD 20814 USA. [Kassem, Layla] NIH, 35 Convent Dr,RM 1A202,MSC 3719, Bethesda, MD 20892 USA. [Brotman, Melissa A.] NIH, 15K North Dr,Room 211, Bethesda, MD 20892 USA. [Leibenluft, Ellen] NIH, 15K North Dr,RM 210,MSC 2670, Bethesda, MD 20892 USA. [McMahon, Francis J.] NIH, 35 Convent Dr,RM 1A201,MSC 3719, Bethesda, MD 20892 USA. RP Cardenas, SA (reprint author), NIH, 10 Ctr Dr,RM 3D54,MSC 1264, Bethesda, MD 20814 USA. EM sac1@williams.edu; kasseml@mail.nih.gov; brotmanm@mail.nih.gov; leibs@mail.nih.gov; mcmahonf@mail.nih.gov RI Brotman, Melissa/H-7409-2013 FU NIMH [1Z01MH002810-11] FX This work was funded by the NIMH Intramural Research Program (1Z01MH002810-11). NR 93 TC 3 Z9 3 U1 9 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 EI 1873-7528 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PD OCT PY 2016 VL 69 BP 193 EP 215 DI 10.1016/j.neubiorev.2016.08.002 PG 23 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA DY7QE UT WOS:000385323500015 PM 27502749 ER PT J AU Luo, J AF Luo, Ji TI Ji Luo elucidates the CRISPR gene editing technology, and how it may affect cancer therapy in the future SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 [Luo, Ji] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA. RP Luo, J (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD OCT PY 2016 VL 30 IS 10 BP 879 EP 879 PG 1 WC Oncology SC Oncology GA DZ2TF UT WOS:000385693800001 ER PT J AU Wentzensen, N AF Wentzensen, Nicolas TI Epidemiology, prevention and early detection of cervical cancer SO ONKOLOGE LA German DT Article DE Cervical cancer; Human papillomaviruses; Screening; Biomarker; Risk-based management ID HPV-POSITIVE WOMEN; HUMAN-PAPILLOMAVIRUS INFECTION; INTRAEPITHELIAL NEOPLASIA; AMERICAN SOCIETY; FOLLOW-UP; METHYLATION; RISK; COLPOSCOPY; PATHOLOGY; VACCINE AB Persisting infections with human papillomaviruses (HPV) are the indisputable cause of cervical cancer. The development of HPV-based preventive procedures, HPV vaccination and HPV testing are currently leading to major changes in cervical cancer prevention programs worldwide. A reduction of HPV infections and cancer precursors has been observed for young women in many countries one decade after the introduction of HPV vaccination. The focus is now on the integration of new testing approaches for screening of populations with increasing vaccination rates. A successful cervical cancer prevention program consists of various components including primary screening, triage of screening positives and colposcopy with biopsy to identify women with precursor cancer stages who require treatment. The role of primary screening is to identify a small subset of women with an increased risk of a precancerous stage, while the majority of women can be reassured that the risk is very low. Depending on the primary screening test, additional triage testing is required to decide who should be referred for colposcopy. Currently, there are three major approaches to cervical cancer screening: cervical cytology, HPV testing and HPV cytology co-testing. Several triage tests for HPV-positive women are currently being evaluated, including cytology, HPV genotyping, p16/Ki-67 cytology and various methylation tests. The increasing number of options for cervical cancer screening represent a challenge for clinical guidelines to remain up to date and comprehensible. The increasing complexity can lead to confusion among providers and women who participate in screening programs about the best approaches. Precision prevention is a novel approach to cervical cancer screening that integrates comprehensive risk data based on the individual medical history with test results for uniform, risk-based management decisions. C1 [Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, Med Ctr Dr,Room 7-E114,9609, Bethesda, MD 20892 USA. RP Wentzensen, N (reprint author), NCI, Div Canc Epidemiol & Genet, Med Ctr Dr,Room 7-E114,9609, Bethesda, MD 20892 USA. EM wentzenn@mail.nih.gov NR 46 TC 0 Z9 0 U1 3 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0947-8965 EI 1433-0415 J9 ONKOLOGE JI Onkologe PD OCT PY 2016 VL 22 IS 10 BP 725 EP 736 DI 10.1007/s00761-016-0092-7 PG 12 WC Oncology SC Oncology GA DY5TS UT WOS:000385166900004 PM 28265177 ER PT J AU Olivier, KN AF Olivier, Kenneth N. TI ANTIMICROBIAL THERAPY: QUESTIONS, CONCERNS AND LOOKING AHEAD SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Olivier, Kenneth N.] NHLBI, Cardiovasc & Pulm Branch, Bldg 10, Bethesda, MD 20892 USA. NR 2 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 OCT PY 2016 VL 51 SU S45 MA S04.2 BP 130 EP 131 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA DY0VW UT WOS:000384815300014 ER PT J AU Goeckeler-Fried, J Estabrooks, SK Chiang, A Chung, W Ye, Z Denny, RA Weissman, AM Camacho, CJ Sorscher, EJ Brodsky, JL AF Goeckeler-Fried, J. Estabrooks, S. K. Chiang, A. Chung, W. Ye, Z. Denny, R. A. Weissman, A. M. Camacho, C. J. Sorscher, E. J. Brodsky, J. L. TI IDENTIFICATION OF NOVEL INHIBITORS OF UBIQUITINATION THAT IMPROVE RESCUE OF F508DEL-CFTR BY VX-809 SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Goeckeler-Fried, J.; Estabrooks, S. K.; Chiang, A.; Brodsky, J. L.] Univ Pittsburgh, Biol Sci, Pittsburgh, PA USA. [Chung, W.] Univ Alabama Birmingham, Neurobiol, Birmingham, AL USA. [Ye, Z.; Camacho, C. J.] Univ Pittsburgh, Computat Biol, Pittsburgh, PA USA. [Denny, R. A.] Pfizer Worldwide Med Chem, Cambridge, MA USA. [Weissman, A. M.] NCI, Lab Prot Dynam & Signaling, Frederick, MD 21701 USA. [Sorscher, E. J.] Emory Univ, Pediat, Atlanta, GA 30322 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 8755-6863 EI 1099-0496 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD OCT PY 2016 VL 51 SU S45 MA 35 BP 206 EP 206 PG 1 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA DY0VW UT WOS:000384815300112 ER PT J AU Liou, TG Adler, FR Brown, P Chatfield, BA Clancy, JP Cox, DR Daines, C Elborn, JS Emmett, P Francis, J Jensen, JL Heynekamp, TR Keogh, RH Lechtzin, N Li, Y Lysinger, J Nakamura, C Olivier, KN Packer, KA Quittner, AL Radford, P Szczesniak, RD Taylor-Cousar, JL Vroom, J Sagel, SD AF Liou, T. G. Adler, F. R. Brown, P. Chatfield, B. A. Clancy, J. P. Cox, D. R. Daines, C. Elborn, J. S. Emmett, P. Francis, J. Jensen, J. L. Heynekamp, T. R. Keogh, R. H. Lechtzin, N. Li, Y. Lysinger, J. Nakamura, C. Olivier, K. N. Packer, K. A. Quittner, A. L. Radford, P. Szczesniak, R. D. Taylor-Cousar, J. L. Vroom, J. Sagel, S. D. TI MOUNTAIN WEST CF CONSORTIUM SPUTUM BIOMARKER STUDY SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Liou, T. G.; Adler, F. R.; Chatfield, B. A.; Francis, J.; Jensen, J. L.; Li, Y.; Packer, K. A.; Vroom, J.] Univ Utah, Salt Lake City, UT USA. [Nakamura, C.] Las Vegas CF Ctr, Las Vegas, NV USA. [Brown, P.] CF Ctr Idaho, Boise, ID USA. [Lysinger, J.] Billings Clin, Billings, MT USA. [Clancy, J. P.; Szczesniak, R. D.] Univ Cincinnati, Cincinnati, OH USA. [Daines, C.] Univ Arizona, Tucson, AZ USA. [Elborn, J. S.] Queens Univ Belfast, Belfast, Antrim, North Ireland. [Cox, D. R.] Univ Oxford Nuffield Coll, Oxford, England. [Emmett, P.; Sagel, S. D.] Univ Colorado, Aurora, CO USA. [Heynekamp, T. R.] Univ New Mexico, Albuquerque, NM 87131 USA. [Keogh, R. H.] London Sch Hyg & Trop Med, London, England. [Lechtzin, N.] Johns Hopkins Univ, Baltimore, MD USA. [Olivier, K. N.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. [Quittner, A. L.] Univ Miami, Miami, FL USA. [Radford, P.] Phoenix Childrens Hosp, Phoenix, AZ USA. [Taylor-Cousar, J. L.] Natl Jewish Hlth, Denver, CO USA. [Sagel, S. D.] Childrens Hosp Colorado, Aurora, CO 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 8755-6863 EI 1099-0496 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD OCT PY 2016 VL 51 SU S45 MA 232 BP 279 EP 280 PG 2 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA DY0VW UT WOS:000384815300309 ER PT J AU Tsuchiya, M Kalurupalle, S Kumar, P Ghoshal, S Zhang, Y Lehrmann, E Becker, K Gorospe, M Biswas, R AF Tsuchiya, M. Kalurupalle, S. Kumar, P. Ghoshal, S. Zhang, Y. Lehrmann, E. Becker, K. Gorospe, M. Biswas, R. TI RPTOR, A NOVEL TARGET OF MICRORNA-155, REGULATES THE FIBROTIC PHENOTYPE OF CYSTIC FIBROSIS LUNG EPITHELIUM THROUGH UP-REGULATION OF CTGF SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Tsuchiya, M.; Kalurupalle, S.; Kumar, P.; Ghoshal, S.; Biswas, R.] USUHS, Anat Physiol & Genet, Bethesda, MD USA. [Zhang, Y.; Lehrmann, E.; Becker, K.; Gorospe, M.] NIA, Genet Lab, NIH, Baltimore, MD 21224 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 8755-6863 EI 1099-0496 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD OCT PY 2016 VL 51 SU S45 MA 237 BP 281 EP 281 PG 1 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA DY0VW UT WOS:000384815300314 ER PT J AU Davidson, RM Hasan, NA Epperson, LE Vasireddy, S Smith, T Elliot, B Olivier, KN Holland, SM Salfinger, ML Nick, JA Zelazny, A Wallace, RJ Daley, CL Strong, M AF Davidson, R. M. Hasan, N. A. Epperson, L. E. Vasireddy, S. Smith, T. Elliot, B. Olivier, K. N. Holland, S. M. Salfinger, M. L. Nick, J. A. Zelazny, A. Wallace, R. J. Daley, C. L. Strong, M. TI GENOMIC AND EVOLUTIONARY ANALYSES OF CLINICAL MYCOBACTERIUM ABSCESSUS SUBSP MASSILIENSE FROM PATIENTS WITH AND WITHOUT CYSTIC FIBROSIS SO PEDIATRIC PULMONOLOGY LA English DT Meeting Abstract C1 [Davidson, R. M.; Hasan, N. A.; Epperson, L. E.; Strong, M.] Natl Jewish Hlth, Ctr Genes Environm & Hlth, Denver, CO USA. [Vasireddy, S.; Smith, T.; Elliot, B.; Wallace, R. J.] Univ Texas Hlth Sci Ctr, Dept Microbiol, Tyler, TX USA. [Salfinger, M. L.; Nick, J. A.; Daley, C. L.] Natl Jewish Hlth, Dept Med, Denver, CO USA. [Olivier, K. N.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. [Holland, S. M.] NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Zelazny, A.] NIH, Dept Microbiol Serv, Dept Lab Med, Bldg 10, 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 8755-6863 EI 1099-0496 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD OCT PY 2016 VL 51 SU S45 MA 392 BP 342 EP 342 PG 1 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA DY0VW UT WOS:000384815300468 ER PT J AU Shiroma, EJ Schepps, MA Harezlak, J Chen, KY Matthews, CE Koster, A Caserotti, P Glynn, NW Harris, TB AF Shiroma, E. J. Schepps, M. A. Harezlak, J. Chen, K. Y. Matthews, C. E. Koster, A. Caserotti, P. Glynn, N. W. Harris, T. B. TI Daily physical activity patterns from hip- and wrist-worn accelerometers SO PHYSIOLOGICAL MEASUREMENT LA English DT Article DE physical activity; epidemiology; exercise; accelerometer; patterns; aging ID SEDENTARY BEHAVIOR; OLDER-ADULTS; AGE; CALIBRATION; MONITORS; OUTPUT; WHITE; SITES; WOMEN; MEN AB Accelerometer wear location may influence physical activity estimates. This study investigates this relationship through the examination of activity patterns throughout the day. Participants from the aging research evaluating accelerometry (AREA) study (n men = 37, n women = 47, mean age (SD) = 78.9 (5.5) years) were asked to wear accelerometers in a free-living environment for 7 d at three different wear locations; one on each wrist and one on the right hip. During waking hours, wrist-worn accelerometers consistently produced higher median activity counts, about 5 x higher, as well as wider variability compared to hip-worn monitors. However, the shape of the accrual pattern curve over the course of the day for the hip and wrist are similar; there is a spike in activity in the morning, with a prolonged tapering of activity level as the day progresses. The similar patterns of hip and wrist activity accrual provide support that each location is capable of estimating total physical activity volume. The examination of activity patterns over time may provide a more detailed way to examine differences in wear location and different subpopulations. C1 [Shiroma, E. J.; Schepps, M. A.; Harris, T. B.] NIA, Lab Epidemiol & Populat Sci, 7201 Wisconsin Ave,Gateway Bldg,Suite 3C309, Bethesda, MD 20892 USA. [Harezlak, J.] Indiana Univ, Richard M Fairbanks Sch Publ Hlth, Dept Biostat, Bloomington, IN 47405 USA. [Harezlak, J.] Indiana Univ, Sch Med, Bloomington, IN 47405 USA. [Chen, K. Y.] NIDDK, Diabet Endocrinol & Obes Branch, Bethesda, MD 20892 USA. [Matthews, C. E.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Koster, A.] Maastricht Univ, CAPHRI Sch Publ Hlth & Primary Care, Dept Social Med, Maastricht, Netherlands. [Caserotti, P.] Univ Southern Denmark, Dept Sports Sci & Clin Biomech, Odense, Denmark. [Glynn, N. W.] Univ Pittsburgh, Grad Sch Publ Hlth, Ctr Aging & Populat Hlth, Pittsburgh, PA USA. RP Shiroma, EJ (reprint author), NIA, Lab Epidemiol & Populat Sci, 7201 Wisconsin Ave,Gateway Bldg,Suite 3C309, Bethesda, MD 20892 USA. EM Eric.shiroma@nih.gov RI Dey, Kamalesh/E-6568-2017; Koster, Annemarie/E-7438-2010; OI Chen, Kong/0000-0002-0306-1904 FU Intramural Research Program of the National Institutes of Health, National Institute on Aging; National Institutes of Health [AG024826, AG024827, AG036594, AG000181]; European Union Seventh Framework Programme (FP7-PEOPLE-CIG) [PCIG09-GA-2011-293621]; National Institute on Aging [HHSN271201 100605P] FX This study was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging and by the research grants AG024826, AG024827, AG036594, and AG000181 from the National Institutes of Health. A Koster has received funding from the European Union Seventh Framework Programme (FP7-PEOPLE-2011-CIG) under grant agreement PCIG09-GA-2011-293621. NW Glynn was supported in part by National Institute on Aging Professional Services Contract HHSN271201 100605P. We are grateful to the staff of the AREA and DECO studies, particularly B S Lange-Maia, M E Garcia, and J R Treinish. NR 25 TC 1 Z9 1 U1 6 U2 6 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0967-3334 EI 1361-6579 J9 PHYSIOL MEAS JI Physiol. Meas. PD OCT PY 2016 VL 37 IS 10 BP 1852 EP 1861 DI 10.1088/0967-3334/37/10/1852 PG 10 WC Biophysics; Engineering, Biomedical; Physiology SC Biophysics; Engineering; Physiology GA DY9ZW UT WOS:000385497200015 PM 27654140 ER PT J AU Karlsson, C Rehman, F Damadzic, R Atkins, AL Schank, JR Gehlert, DR Steensland, P Thorsell, A Heilig, M AF Karlsson, Camilla Rehman, Faazal Damadzic, Ruslan Atkins, Alison L. Schank, Jesse R. Gehlert, Donald R. Steensland, Pia Thorsell, Annika Heilig, Markus TI The melanin-concentrating hormone-1 receptor modulates alcohol-induced reward and DARPP-32 phosphorylation (vol 233, pg 2355, 2016) SO PSYCHOPHARMACOLOGY LA English DT Correction C1 [Karlsson, Camilla; Atkins, Alison L.; Thorsell, Annika; Heilig, Markus] Linkopings Univ, Dept Clin & Expt Med, Linkoping, Sweden. [Rehman, Faazal; Damadzic, Ruslan] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. [Schank, Jesse R.] Univ Georgia, Dept Physiol & Pharmacol, Athens, GA 30602 USA. [Gehlert, Donald R.] Lilly Res Labs, Neurosci & Endocrine Discovery Res, Indianapolis, IN USA. [Steensland, Pia] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. RP Heilig, M (reprint author), Linkopings Univ, Dept Clin & Expt Med, Linkoping, Sweden. EM markus.heilig@liu.se NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD OCT PY 2016 VL 233 IS 21-22 BP 3825 EP 3825 DI 10.1007/s00213-016-4434-3 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA DZ0HM UT WOS:000385518500015 PM 27650828 ER PT J AU Murad, H Kipnis, V Freedman, LS AF Murad, Havi Kipnis, Victor Freedman, Laurence S. TI Estimating and testing interactions when explanatory variables are subject to non-classical measurement error SO STATISTICAL METHODS IN MEDICAL RESEARCH LA English DT Article DE measurement error (ME); errors in variables; interaction; regression calibration (RC); linear regression calibration; efficient regression calibration; type I error probability; power ID STRUCTURAL EQUATION MODELS; REGRESSION CALIBRATION; NUTRITIONAL EPIDEMIOLOGY AB Assessing interactions in linear regression models when covariates have measurement error (ME) is complex. We previously described regression calibration (RC) methods that yield consistent estimators and standard errors for interaction coefficients of normally distributed covariates having classical ME. Here we extend normal based RC (NBRC) and linear RC (LRC) methods to a non-classical ME model, and describe more efficient versions that combine estimates from the main study and internal sub-study. We apply these methods to data from the Observing Protein and Energy Nutrition (OPEN) study. Using simulations we show that (i) for normally distributed covariates efficient NBRC and LRC were nearly unbiased and performed well with sub-study size 200; (ii) efficient NBRC had lower MSE than efficient LRC; (iii) the naive test for a single interaction had type I error probability close to the nominal significance level, whereas efficient NBRC and LRC were slightly anti-conservative but more powerful; (iv) for markedly non-normal covariates, efficient LRC yielded less biased estimators with smaller variance than efficient NBRC. Our simulations suggest that it is preferable to use: (i) efficient NBRC for estimating and testing interaction effects of normally distributed covariates and (ii) efficient LRC for estimating and testing interactions for markedly non-normal covariates. C1 [Murad, Havi; Freedman, Laurence S.] Gertner Inst Epidemiol & Hlth Policy Res, Biostat Unit, IL-52621 Tel Hashomer, Israel. [Kipnis, Victor] NCI, Biometry Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. RP Murad, H (reprint author), Gertner Inst Epidemiol & Hlth Policy Res, Biostat Unit, IL-52621 Tel Hashomer, Israel. EM HaviM@gertner.health.gov.il FU Marcia and Eugene Applebaum, Detroit, MI, USA; United States-Israel Educational Foundation (USIEF) FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by the Doctoral Fellowship of Excellence grant, awarded to Bar-Ilan University, Israel by Marcia and Eugene Applebaum, Detroit, MI, USA. Apart of this research was done during a three months visit to the National Cancer Institute, Biometry Research Division, USA supported by the Fulbright Grant for Doctoral Dissertation Students, awarded by the United States-Israel Educational Foundation (USIEF). NR 19 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0962-2802 EI 1477-0334 J9 STAT METHODS MED RES JI Stat. Methods Med. Res. PD OCT PY 2016 VL 25 IS 5 BP 1991 EP 2013 DI 10.1177/0962280213509720 PG 23 WC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Mathematics GA DZ0UO UT WOS:000385555400015 PM 24334284 ER PT J AU Mulatya, CM McLain, AC Cai, B Hardin, JW Albert, PS AF Mulatya, Caroline M. McLain, Alexander C. Cai, Bo Hardin, James W. Albert, Paul S. TI Estimating time to event characteristics via longitudinal threshold regression models - an application to cervical dilation progression SO STATISTICS IN MEDICINE LA English DT Article DE first hitting time; threshold regression; Weiner process ID NULLIPAROUS WOMEN; LABOR CURVE; INTERVAL; OUTCOMES AB In longitudinal studies, it is sometimes of interest to estimate the distribution of the time a longitudinal process takes to traverse from one threshold to another. For example, the distribution of the time it takes a woman's cervical dilation to progress from 3 to 4cm can aid the decision-making of obstetricians as to whether a stalled labor should be allowed to proceed or stopped in favor of other options. Often researchers treat this type of data structure as interval censored and employ traditional survival analysis methods. However, the traditional interval censoring approaches are inefficient in that they do not use all of the available data. In this paper, we propose utilizing a longitudinal threshold model to estimate the distribution of the elapsed time between two thresholds of the longitudinal process from repeated measurements. We extend this modeling framework to be used with multiple thresholds. A Wiener process under the first hitting time framework is used to represent survival distribution. We demonstrate our model through simulation studies and an analysis of data from the Consortium on Safe Labor study. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. C1 [Mulatya, Caroline M.; McLain, Alexander C.; Cai, Bo; Hardin, James W.] Univ South Carolina, Dept Epidemiol & Biostat, 915 Greene St, Columbia, SC 29208 USA. [Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, 6100 Execut Blvd, Rockville, MD 20852 USA. RP McLain, AC (reprint author), Univ South Carolina, Dept Epidemiol & Biostat, 915 Greene St, Columbia, SC 29208 USA. EM mclaina@mailbox.sc.edu RI Hardin, James/Q-7617-2016 OI Hardin, James/0000-0003-0506-5500 FU Intramural Research Program of the National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development; Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development FX We thank the editor, associate editor, and two anonymous referees for their helpful comments, which greatly improved this manuscript. We thank the Intramural Research Program of the National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development for allowing us to use these data from the CSL study. The research by Dr. Albert was supported by the Intramural Research Program of the National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development. The research by Dr. McLain was supported, in part, by an Interpersonal Agreement with the Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 28 TC 0 Z9 0 U1 4 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD OCT PY 2016 VL 35 IS 24 BP 4368 EP 4379 DI 10.1002/sim.7031 PG 12 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA DY9XQ UT WOS:000385490200006 PM 27405611 ER PT J AU Follmann, D Huang, CY Gabriel, E AF Follmann, Dean Huang, Chiung-Yu Gabriel, Erin TI Who really gets strep sore throat? Confounding and effect modification of a time-varying exposure on recurrent events SO STATISTICS IN MEDICINE LA English DT Article DE attributable fraction; case-crossover design; pattern mixture models; probability of causation; self-controlled case series ID CASE-CROSSOVER DESIGN; CAUSAL INFERENCE; CASE SERIES; TESTS; RISK; BIAS AB Unmeasured confounding is the fundamental obstacle to drawing causal conclusions about the impact of an intervention from observational data. Typically, covariates are measured to eliminate or ameliorate confounding, but they may be insufficient or unavailable. In the special setting where a transient intervention or exposure varies over time within each individual and confounding is time constant, a different tack is possible. The key idea is to condition on either the overall outcome or the proportion of time in the intervention. These measures can eliminate the unmeasured confounding either by conditioning or by use of a proxy covariate. We evaluate existing methods and develop new models from which causal conclusions can be drawn from such observational data even if no baseline covariates are measured. Our motivation for this work was to determine the causal effect of Streptococcus bacteria in the throat on pharyngitis (sore throat) in Indian schoolchildren. Using our models, we show that existing methods can be badly biased and that sick children who are rarely colonized have a high probability that the Streptococcus bacteria are causing their disease. Published 2016. This article is a U.S. Government work and is in the public domain in the USA C1 [Follmann, Dean; Gabriel, Erin] NIAID, Biostat Res Branch, NIH, 5601 Fishers Lane Room 4C11, Rockville, MD 20852 USA. [Huang, Chiung-Yu] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA. [Huang, Chiung-Yu] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. RP Follmann, D (reprint author), NIAID, Biostat Res Branch, NIH, 5601 Fishers Lane Room 4C11, Rockville, MD 20852 USA. EM dean.follmann@nih.gov OI Gabriel, Erin/0000-0002-0504-8404 FU National Institutes of Health [1R01CA193888] FX Huang's work was sponsored by the National Institutes of Health grant 1R01CA193888. NR 26 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD OCT PY 2016 VL 35 IS 24 BP 4398 EP 4412 DI 10.1002/sim.7000 PG 15 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA DY9XQ UT WOS:000385490200008 PM 27313096 ER PT J AU Asdaghi, N Romano, JG Wang, KF Ciliberti-Vargas, MA Koch, S Gardener, H Dong, CH Rose, DZ Waddy, SP Robichaux, M Garcia, EJ Gonzalez-Sanchez, JA Burgin, WS Sacco, RL Rundek, T AF Asdaghi, Negar Romano, Jose G. Wang, Kefeng Ciliberti-Vargas, Maria A. Koch, Sebastian Gardener, Hannah Dong, Chuanhui Rose, David Z. Waddy, Salina P. Robichaux, Mary Garcia, Enid J. Gonzalez-Sanchez, Juan A. Burgin, W. Scott Sacco, Ralph L. Rundek, Tatjana TI Sex Disparities in Ischemic Stroke Care FL-PR CReSD Study (Florida-Puerto Rico Collaboration to Reduce Stroke Disparities) SO STROKE LA English DT Article DE Get With The Guidelines; National Institute of Neurological Disorders and Stroke; sex characteristics; stroke ID AMERICAN-HEART-ASSOCIATION; IN-HOSPITAL MORTALITY; EMERGENCY-DEPARTMENT; GENDER-DIFFERENCES; WOMEN; IMPROVEMENT; OUTCOMES; REGISTRY; PROGRAM; FUTURE AB Background and Purpose-Sex-specific disparities in stroke care including thrombolytic therapy and early hospital admission are reported. In a large registry of Florida and Puerto Rico hospitals participating in the Get With The GuidelinesStroke program, we sought to determine sex-specific differences in ischemic stroke performance metrics and overall thrombolytic treatment. Methods-Around 51317 (49% women) patients were included from 73 sites from 2010 to 2014. Multivariable logistic regression with generalized estimating equations evaluated sex-specific differences in the prespecified Get With The GuidelinesStroke metrics for defect-free care in ischemic stroke, adjusting for age, race-ethnicity, insurance status, hospital characteristics, individual risk factors, and the presenting stroke severity. Results-As compared with men, women were older (7315 versus 69 +/- 14 years; P<0.0001), more hypertensive (67% versus 63%, P<0.0001), and had more atrial fibrillation (19% versus 16%; P<0.0001). Defect-free care was slightly lower in women than in men (odds ratio, 0.96; 95% confidence interval, 0.93-1.00). Temporal trends in defect-free care improved substantially and similarly for men and women, with a 29% absolute improvement in women (P<0.0001) and 28% in men (P<0.0001), with P value of 0.13 for time-by-sex interaction. Women were less likely to receive thrombolysis (odds ratio, 0.92; 95% confidence interval, 0.86-0.99; P=0.02) and less likely to have a door-to-needle time <1 hour (odds ratio, 0.83; 95% confidence interval, 0.71-0.97; P=0.02) as compared with men. Conclusions-Women received comparable stroke care to men in this registry as measured by prespecified Get With The Guidelines metrics. However, women less likely received thrombolysis and had door-to-needle time <1 hour, an observation that calls for the implementation of interventions to reduce sex disparity in these measures. C1 [Asdaghi, Negar; Romano, Jose G.; Wang, Kefeng; Ciliberti-Vargas, Maria A.; Koch, Sebastian; Gardener, Hannah; Dong, Chuanhui; Sacco, Ralph L.; Rundek, Tatjana] Univ Miami, Miller Sch Med, Dept Neurol, Coral Gables, FL 33124 USA. [Rose, David Z.; Burgin, W. Scott] Univ S Florida, Sch Med, Dept Neurol, Tampa, FL USA. [Waddy, Salina P.] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Robichaux, Mary] Amer Heart Assoc, Greater Southeast Affiliate, Marietta, GA USA. [Garcia, Enid J.] Univ Puerto Rico, Sch Med, Endowed Hlth Serv Res Ctr, San Juan, PR 00936 USA. [Gonzalez-Sanchez, Juan A.] Univ Puerto Rico, Sch Med, Dept Emergency Med, San Juan, PR 00936 USA. RP Asdaghi, N (reprint author), 1120 NW 14th St,Clin Res Bldg,13th Floor, Miami, FL 33136 USA. EM nasdaghi@med.miami.edu FU National Institute of Health (NIH)/National Institute of Neurological Disorders (NINDs) and Stroke Prevention and Intervention Research Program (SPIRP) cooperative grant [U54NS081763]; Office of Research on Women's Health [3U54NS081763-01S1] FX The Florida Puerto Rico Collaboration to Reduce Stroke Disparities Study is supported by the National Institute of Health (NIH)/National Institute of Neurological Disorders (NINDs) and Stroke Prevention and Intervention Research Program (SPIRP) cooperative grant (grant number: U54NS081763). The women's supplement is awarded from the Office of Research on Women's Health (Grant Number: 3U54NS081763-01S1). NR 29 TC 1 Z9 1 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD OCT PY 2016 VL 47 IS 10 BP 2618 EP 2626 DI 10.1161/STROKEAHA.116.013059 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA DY8VV UT WOS:000385410700037 PM 27553032 ER PT J AU Allen, ES Klein, HG AF Allen, Elizabeth S. Klein, Harvey G. TI In a digital age, a relic of manual transfusion records SO TRANSFUSION LA English DT Editorial Material C1 [Allen, Elizabeth S.; Klein, Harvey G.] NIH, Dept Transfus Med, Ctr Clin, 10 Ctr Dr,MSC 1184,Bldg 10,Room 1C-711, Bethesda, MD 20892 USA. RP Allen, ES (reprint author), NIH, Dept Transfus Med, Ctr Clin, 10 Ctr Dr,MSC 1184,Bldg 10,Room 1C-711, Bethesda, MD 20892 USA. EM elizabeth.allen@nih.gov OI Allen, Elizabeth/0000-0002-1004-3851 NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD OCT PY 2016 VL 56 IS 10 BP 2405 EP 2405 DI 10.1111/trf.13665 PG 1 WC Hematology SC Hematology GA DZ4NG UT WOS:000385834800003 PM 27739156 ER PT J AU Srivastava, K Polin, H Sheldon, SL Wagner, FF Grabmer, C Gabriel, C Denomme, GA Flegel, WA AF Srivastava, Kshitij Polin, Helene Sheldon, Sherry Lynne Wagner, Franz Friedrich Grabmer, Christoph Gabriel, Christian Denomme, Gregory Andrew Flegel, Willy Albert TI The DAU cluster: a comparative analysis of 18 RHD alleles, some forming partial D antigens SO TRANSFUSION LA English DT Article ID SICKLE-CELL-DISEASE; AMINO-ACID SUBSTITUTIONS; PROTEIN-STRUCTURE; TRANSFUSION THERAPY; CLINICALLY RELEVANT; MOLECULAR-GENETICS; RHESUS-BOX; D VARIANTS; PHENOTYPE; ENCODES AB BACKGROUNDThe Rh system is the most complex and polymorphic blood group system in humans with more than 460 alleles known for the RHD gene. The DAU cluster of RHD alleles is characterized by the single-nucleotide change producing the p.Thr379Met amino acid substitution. It is called the DAU-0 allele and has been postulated to be the primordial allele, from which all other alleles of the DAU cluster have eventually evolved. STUDY DESIGN AND METHODSFor two novel DAU alleles, the nucleotide sequences of all 10 exons as well as adjacent intronic regions, including the 5 and 3 untranslated regions (UTR), were determined for the RHD and RHCE genes. A phylogenetic tree for all DAU alleles was established using the neighbor-joining method with Pan troglodytes as root. Standard hemagglutination and flow cytometry tests were performed. RESULTSWe characterized two DAU alleles, DAU-11 and DAU-5.1, closely related to DAU-3 and DAU-5, respectively. A phylogenetic analysis of the 18 known DAU alleles indicated point mutations and interallelic recombination contributing to diversification of the DAU cluster. CONCLUSIONSThe DAU alleles encode a group of RhD protein variants, some forming partial D antigens known to permit anti-D in carriers; all are expected to cause anti-D alloimmunization in recipients of red blood cell transfusions. The DAU alleles evolved through genomic point mutations and recombination. These results suggest that the cluster of DAU alleles represent a clade, which is concordant with our previous postulate that they derived from the primordial DAU-0 allele. C1 [Srivastava, Kshitij; Sheldon, Sherry Lynne; Flegel, Willy Albert] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Polin, Helene; Gabriel, Christian] Red Cross Transfus Serv Upper Austria, Linz, Austria. [Wagner, Franz Friedrich] Inst Springe, Red Cross Blood Serv NSTOB, Springe, Germany. [Grabmer, Christoph] SALK Paracelsus Med Univ, Dept Blood Grp Serol & Transfus Med, Salzburg, Austria. [Gabriel, Christian] Med Univ Graz, Dept Blood Grp Serol & Transfus Med, Graz, Austria. [Denomme, Gregory Andrew] BloodCtr Wisconsin, Diagnost Labs, Milwaukee, WI USA. RP Flegel, WA (reprint author), NIH, Lab Serv Sect, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM waf@nih.gov OI Denomme, Gregory/0000-0001-8727-1679 NR 67 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD OCT PY 2016 VL 56 IS 10 BP 2520 EP 2531 DI 10.1111/trf.13739 PG 12 WC Hematology SC Hematology GA DZ4NG UT WOS:000385834800018 PM 27480171 ER PT J AU Rooney, MR Pankow, JS Sibley, SD Selvin, E Reis, JP Michos, ED Lutsey, PL AF Rooney, Mary R. Pankow, James S. Sibley, Shalamar D. Selvin, Elizabeth Reis, Jared P. Michos, Erin D. Lutsey, Pamela L. TI Serum calcium and incident type 2 diabetes: the Atherosclerosis Risk in Communities (ARIC) study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE calcium-sensing receptor polymorphism; cohort study; diabetes mellitus; race; serum calcium ID GENOME-WIDE ASSOCIATION; CYTOSOLIC-FREE CALCIUM; PARATHYROID-HORMONE; INSULIN-RESISTANCE; RACIAL-DIFFERENCES; VITAMIN-D; CARDIOVASCULAR RISK; 25-HYDROXYVITAMIN D; BLACK-WOMEN; GLUCOSE AB Background: Elevated serum calcium has been associated with a variety of metabolic abnormalities and may be associated with a greater risk of diabetes. Objective: The purpose of this study was to test the hypothesis that serum calcium concentration is positively and independently associated with the incidence of diabetes and to evaluate the association of calcium-sensing receptor (CaSR) gene single nucleotide polymorphism (SNP) rs1801725 with incident diabetes. Design: Atherosclerosis Risk in Communities study participants free of diabetes at baseline (n = 12,800; mean age: 53.9 y; 22.6% black) were studied for incident diabetes. Serum calcium was measured at baseline and corrected for serum albumin. Diabetes was defined by use of glucose concentrations, self-report, or medication use. Cox proportional hazards regression was used. Results: During a mean 8.8 y of follow-up, 1516 cases of diabetes were reported. Participants in the highest compared with lowest calcium quintile were at greater risk of incident diabetes after adjustment for demographic and lifestyle factors [BR (95% CI): 1.34 (1.14, 1.57); P-trend across quintiles <0.0001] and with further adjustment for waist circumference and body mass index [1.26 (1.07, 1.48); P-trend = 0.004]. Additional adjustment for biomarkers on the metabolic pathway (e.g., 25-hydroxyvitamin D, parathyroid hormone, phosphorus) had little impact. The calcium-diabetes association was statistically significant in blacks [1.48 (1.11, 1.98); P-trend = 0.002] but not whites [1.17 (0.96, 1.43); P-trend = 0.17] after adjustment for adiposity. In whites, CaSR gene SNP rs1801725 was associated with serum calcium but not with risk of diabetes. Conclusions: Consistent with 3 previous cohort studies, elevated serum calcium was found to be associated with a greater risk of type 2 diabetes. Further research is needed to understand the role, if any, that calcium plays in the pathogenesis of diabetes. C1 [Rooney, Mary R.; Pankow, James S.; Lutsey, Pamela L.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA. [Sibley, Shalamar D.] Univ Minnesota, Div Endocrinol & Diabet, Minneapolis, MN 55455 USA. [Selvin, Elizabeth; Michos, Erin D.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21205 USA. [Selvin, Elizabeth; Michos, Erin D.] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA. [Michos, Erin D.] Johns Hopkins Univ, Div Cardiol, Baltimore, MD 21205 USA. [Reis, Jared P.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. RP Rooney, MR (reprint author), Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA. EM roone166@umn.edu FU NIH National Heart, Lung, and Blood Institute [R01 HL103706]; NIH Office of Dietary Supplements [R01 HL103706-S1]; National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK089174]; National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]; NHLBI Candidate Gene Resource grant [N01-HC-65226] FX The research was supported by grants from the NIH National Heart, Lung, and Blood Institute (R01 HL103706 to PLL), the NIH Office of Dietary Supplements (R01 HL103706-S1 to PLL), and the National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK089174 to ES). The Atherosclerosis Risk in Communities study is a collaborative study supported by National Heart, Lung, and Blood Institute contracts HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C. Reagents for the serum albumin assays were donated by the manufacturers. Genotyping was supported through NHLBI Candidate Gene Resource grant no. N01-HC-65226. NR 42 TC 1 Z9 1 U1 5 U2 5 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 OCT PY 2016 VL 104 IS 4 BP 1023 EP 1029 DI 10.3945/ajcn.115.130021 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DY1SO UT WOS:000384874900013 PM 27510541 ER PT J AU Ahluwalia, N Herrick, KA Rossen, LM Rhodes, D Kit, B Moshfegh, A Dodd, KW AF Ahluwalia, Namanjeet Herrick, Kirsten A. Rossen, Lauren M. Rhodes, Donna Kit, Brian Moshfegh, Alanna Dodd, Kevin W. TI Usual nutrient intakes of US infants and toddlers generally meet or exceed Dietary Reference Intakes: findings from NHANES 2009-2012 SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE infants and toddlers; nationally representative sample; nutrient adequacy; recommended intakes; usual nutrient intake ID NATIONAL-HEALTH; PRESCHOOL-CHILDREN; FEEDING INFANTS; TOTAL-ENERGY; NUTRITION; COLLECTION; AMERICA; BIRTH; FOODS; B-24 AB Background: To our knowledge, few studies have described the usual nutrient intakes of US children aged <2 y or assessed the nutrient adequacy of their diets relative to the recommended Dietary Reference Intakes (DRIs). Objective: We estimated the usual nutrient intake of US children aged 6-23 mo examined in NHANES 2009-2012 and compared them to age-specific DRIs as applicable. Design: Dietary intake was assessed with two 24-h recalls for infants aged 6-11 mo (n = 381) and toddlers aged 12-23 mo (n = 516) with the use of the USDA's Automated Multiple-Pass Method. Estimates of usual nutrient intakes from food and beverages were obtained with the use of the National Cancer Institute method. The proportions of children with intakes below and above the DRI were also estimated. Results: The estimated usual intakes of infants were adequate for most nutrients; however, 10% had an iron intake below the Estimated Average Requirement (EAR), and only 21% had a vitamin D intake that met or exceeded the recommended Adequate Intake (AI). More nutrient inadequacies were noted among toddlers; 1 in 4 had a lower-than-recommended fat intake (percentage of energy), and most had intakes that were below the EAR for vitamins E (82%) and D (74%). Few toddlers (<1%) met or exceeded the AI for fiber and potassium. In contrast, 1 in 2 had sodium intakes that exceeded the Tolerable Upper Intake Level (UL); >= 16% and 41% of the children had excessive intakes (greater than the ULs) of vitamin A and zinc, respectively. Conclusions: The estimated usual intakes of infants were adequate for most nutrients. Most toddlers were at risk for inadequate intakes of vitamins D and E and had diets low in fiber and potassium. The sources contributing to excessive intakes of vitamin A and zinc among infants and toddlers may need further evaluation. C1 [Ahluwalia, Namanjeet; Herrick, Kirsten A.; Kit, Brian] CDC, Div Hlth & Nutr Examinat Survey, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. [Rossen, Lauren M.] CDC, Off Anal & Epidemiol, Natl Ctr Hlth Stat, Hyattsville, MD USA. [Rhodes, Donna; Moshfegh, Alanna] USDA, Food Surveys Res Grp, Beltsville, MD 20705 USA. [Dodd, Kevin W.] NCI, NIH, Rockville, MD USA. RP Ahluwalia, N (reprint author), CDC, Div Hlth & Nutr Examinat Survey, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. EM n.ahluwalia@cdc.gov NR 40 TC 2 Z9 2 U1 8 U2 8 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 OCT PY 2016 VL 104 IS 4 BP 1167 EP 1174 DI 10.3945/ajcn.116.137752 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DY1SO UT WOS:000384874900029 PM 27629049 ER PT J AU Yanik, EL Nogueira, LM Koch, L Copeland, G Lynch, CF Pawlish, KS Finch, JL Kahn, AR Hernandez, BY Segev, DL Pfeiffer, RM Snyder, JJ Kasiske, BL Engels, EA AF Yanik, E. L. Nogueira, L. M. Koch, L. Copeland, G. Lynch, C. F. Pawlish, K. S. Finch, J. L. Kahn, A. R. Hernandez, B. Y. Segev, D. L. Pfeiffer, R. M. Snyder, J. J. Kasiske, B. L. Engels, E. A. TI Comparison of Cancer Diagnoses Between the US Solid Organ Transplant Registry and Linked Central Cancer Registries SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article ID RECIPIENTS; RISK; MALIGNANCIES AB US transplant centers are required to report cancers in transplant recipients to the transplant network. The accuracy and completeness of these data, collected in the Scientific Registry of Transplant Recipients (SRTR), are unknown. We compared diagnoses in the SRTR and 15 linked cancer registries for colorectal, liver, lung, breast, prostate and kidney cancers; melanoma; and non-Hodgkin lymphoma (NHL). Among 187 384 transplants, 9323 cancers were documented in the SRTR or cancer registries. Only 36.8% of cancers were in both, with 47.5% and 15.7% of cases additionally documented solely in cancer registries or the SRTR, respectively. Agreement between the SRTR and cancer registries varied (kappa = 0.28 for liver cancer and kappa = 0.52-0.66 for lung, prostate, kidney, colorectum, and breast cancers). Upon evaluation, some NHLs documented only in cancer registries were identified in the SRTR as another type of posttransplant lymphoproliferative disorder. Some SRTR-only cases were explained by miscoding (colorectal cancer instead of anal cancer, metastases as lung or liver cancers) or missed matches with cancer registries, partly due to recipients' outmigration from catchment areas. Estimated sensitivity for identifying cancer was 52.5% for the SRTR and 84.3% for cancer registries. In conclusion, SRTR cancer data are substantially incomplete, limiting their usefulness for surveillance and research. C1 [Yanik, E. L.; Pfeiffer, R. M.; Engels, E. A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Nogueira, L. M.] Texas Dept State Hlth Serv, Texas Canc Registry, Austin, TX USA. [Koch, L.] Illinois Dept Publ Hlth, Illinois State Canc Registry, Springfield, IL 62761 USA. [Copeland, G.] Michigan Dept Hlth & Human Serv, Michigan Canc Surveillance Program, Lansing, MI USA. [Lynch, C. F.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. [Pawlish, K. S.] New Jersey Dept Hlth, Canc Epidemiol Serv, New Jersey State Canc Registry, Trenton, NJ USA. [Finch, J. L.] Colorado Dept Publ Hlth & Environm, Colorado Cent Canc Registry, Denver, CO USA. [Kahn, A. R.] New York State Dept Hlth, New York State Canc Registry, Albany, NY USA. [Hernandez, B. Y.] Univ Hawaii, Ctr Canc, Honolulu, HI USA. [Segev, D. L.] Johns Hopkins Med Inst, Dept Surg, Baltimore, MD 21205 USA. [Snyder, J. J.; Kasiske, B. L.] Minneapolis Med Res Fdn Inc, Sci Registry Transplant Recipients, Minneapolis, MN USA. RP Engels, EA (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM engelse@exchange.nih.gov OI Yanik, Elizabeth/0000-0002-5835-0201 FU Intramural Research Program of the National Cancer Institute; Minneapolis Medical Research Foundation, Minneapolis, MN [HHSH250201500009C]; Surveillance, Epidemiology, and End Results Program of the National Cancer Institute: California [HHSN261201000036C, HHSN261201000035C, HHSN261201000034C]; Surveillance, Epidemiology, and End Results Program of the National Cancer Institute: Connecticut [HHSN 261201000024C]; Surveillance, Epidemiology, and End Results Program of the National Cancer Institute: Hawaii [HHSN261201000037C, N01-PC-35137, N01-PC-35139]; Surveillance, Epidemiology, and End Results Program of the National Cancer Institute: Iowa [HSN261201000032C, N01-PC-35143]; Surveillance, Epidemiology, and End Results Program of the National Cancer Institute: New Jersey [HHSN261201300021I, N01-PC-2013-00021]; Surveillance, Epidemiology, and End Results Program of the National Cancer Institute: Seattle-Puget Sound [N01-PC-35142]; Surveillance, Epidemiology, and End Results Program of the National Cancer Institute: Utah [HHSN2612013000171]; National Program of Cancer Registries of the Centers for Disease Control and Prevention: California [1U58 DP000807-01]; National Program of Cancer Registries of the Centers for Disease Control and Prevention: Colorado [U58 DP000848-04]; National Program of Cancer Registries of the Centers for Disease Control and Prevention: Georgia [5U58DP003875-01]; National Program of Cancer Registries of the Centers for Disease Control and Prevention: Illinois [5U58DP003883-03]; National Program of Cancer Registries of the Centers for Disease Control and Prevention: Maryland [U58DP12-1205 3919-03]; National Program of Cancer Registries of the Centers for Disease Control and Prevention: Michigan [5U58DP003921-03]; National Program of Cancer Registries of the Centers for Disease Control and Prevention: New Jersey [5U58/DP003931-02]; National Program of Cancer Registries of the Centers for Disease Control and Prevention: New York [U58DP003879]; National Program of Cancer Registries of the Centers for Disease Control and Prevention: North Carolina [U58DP00 0832]; National Program of Cancer Registries of the Centers for Disease Control and Prevention: Texas [5U58DP000824-04]; state of California; state of Colorado; state of Connecticut; state of Illinois; state of Iowa; state of Massachusetts [5458DP003920] FX This research was supported in part by the Intramural Research Program of the National Cancer Institute. The authors gratefully acknowledge the support and assistance provided by individuals at the Health Resources and Services Administration (Monica Lin), the SRTR (Ajay Israni and Paul Newkirk) and the following cancer registries: the states of California (Tina Clarke), Colorado, Connecticut (Lou Gonsalves), Georgia, Hawaii (Brenda Hernandez), Iowa, Illinois, Michigan, New Jersey (Xiaoling Niu), New York, North Carolina (Chandrika Rao), Texas, Utah (Janna Harrell), and the Seattle-Puget Sound area of Washington (Margaret Madeleine). We also thank analysts at Information Management Services for programming support (David Castenson, Matthew Chaloux, Michael Curry, and Ruth Parsons). The SRTR is currently operated under contract number HHSH250201500009C (Health Resources and Services Administration) by the Minneapolis Medical Research Foundation, Minneapolis, MN. Previously, the SRTR was managed under contracts HHSH250201000018C and HHSH234200537009C. The following cancer registries were supported by the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute: California (contracts HHSN261201000036C, HHSN261201000035C and HHSN261201000034C); Connecticut (HHSN 261201000024C); Hawaii (HHSN261201000037C, N01-PC-35137 and N01-PC-35139); Iowa (HSN261201000032C and N01-PC-35143); New Jersey (HHSN261201300021I and N01-PC-2013-00021); Seattle-Puget Sound (N01-PC-35142); and Utah (HHSN2612013000171). The following cancer registries were supported by the National Program of Cancer Registries of the Centers for Disease Control and Prevention: California (agreement 1U58 DP000807-01), Colorado (U58 DP000848-04), Georgia (5U58DP003875-01), Illinois (5U58DP003883-03), Maryland (U58DP12-1205 3919-03), Michigan (5U58DP003921-03), New Jersey (5U58/DP003931-02), New York (U58DP003879), North Carolina (U58DP00 0832), and Texas (5U58DP000824-04). Additional support was provided by the states of California, Colorado, Connecticut, Illinois, Iowa, Massachusetts (Massachusetts Cancer Prevention and Control Cooperative Agreement 5458DP003920), New Jersey, New York (including the Cancer Surveillance Improvement Initiative), Texas, Utah, and Washington, as well as the University of Utah and the Fred Hutchinson Cancer Research Center in Seattle, WA. NR 12 TC 1 Z9 1 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD OCT PY 2016 VL 16 IS 10 BP 2986 EP 2993 DI 10.1111/ajt.13818 PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA DY0UA UT WOS:000384810500025 ER PT J AU Ferrer, RA Klein, WMP Persoskie, A Avishai-Yitshak, A Sheeran, P AF Ferrer, Rebecca A. Klein, William M. P. Persoskie, Alexander Avishai-Yitshak, Aya Sheeran, Paschal TI The Tripartite Model of Risk Perception (TRIRISK): Distinguishing Deliberative, Affective, and Experiential Components of Perceived Risk SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article DE Risk perception; Vulnerability; Susceptibility; Behavior; Cancer ID HEALTH BELIEF MODEL; BREAST-CANCER; DECISION-MAKING; MECHANICAL TURK; BEHAVIOR; METAANALYSIS; INTENTIONS; JUDGMENT; WORRY; VACCINATION AB Although risk perception is a key predictor in health behavior theories, current conceptions of risk comprise only one (deliberative) or two (deliberative vs. affective/experiential) dimensions. This research tested a tripartite model that distinguishes among deliberative, affective, and experiential components of risk perception. In two studies, and in relation to three common diseases (cancer, heart disease, diabetes), we used confirmatory factor analyses to examine the factor structure of the tripartite risk perception (TRIRISK) model and compared the fit of the TRIRISK model to dual-factor and single-factor models. In a third study, we assessed concurrent validity by examining the impact of cancer diagnosis on (a) levels of deliberative, affective, and experiential risk perception, and (b) the strength of relations among risk components, and tested predictive validity by assessing relations with behavioral intentions to prevent cancer. The tripartite factor structure was supported, producing better model fit across diseases (studies 1 and 2). Inter-correlations among the components were significantly smaller among participants who had been diagnosed with cancer, suggesting that affected populations make finer-grained distinctions among risk perceptions (study 3). Moreover, all three risk perception components predicted unique variance in intentions to engage in preventive behavior (study 3). The TRIRISK model offers both a novel conceptualization of health-related risk perceptions, and new measures that enhance predictive validity beyond that engendered by unidimensional and bidimensional models. The present findings have implications for the ways in which risk perceptions are targeted in health behavior change interventions, health communications, and decision aids. C1 [Ferrer, Rebecca A.; Klein, William M. P.] NCI, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD 20850 USA. [Persoskie, Alexander] NCI, Behav Res Program, Div Canc Control & Populat Sci, Silver Spring, MD USA. [Avishai-Yitshak, Aya; Sheeran, Paschal] Univ North Carolina Chapel Hill, Chapel Hill, NC USA. RP Ferrer, RA (reprint author), NCI, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD 20850 USA. EM ferrerra@mail.nih.gov NR 61 TC 0 Z9 0 U1 11 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD OCT PY 2016 VL 50 IS 5 BP 653 EP 663 DI 10.1007/s12160-016-9790-z PG 11 WC Psychology, Multidisciplinary SC Psychology GA DY5ZI UT WOS:000385184000003 PM 26961206 ER PT J AU Shomaker, LB Kelly, NR Pickworth, CK Cassidy, OL Radin, RM Shank, LM Vannucci, A Thompson, KA Armaiz-Flores, SA Brady, SM Demidowich, AP Galescu, OA Courville, AB Olsen, C Chen, KY Stice, E Tanofsky-Kraff, M Yanovski, JA AF Shomaker, Lauren B. Kelly, Nichole R. Pickworth, Courtney K. Cassidy, Omni L. Radin, Rachel M. Shank, Lisa M. Vannucci, Anna Thompson, Katherine A. Armaiz-Flores, Sara A. Brady, Sheila M. Demidowich, Andrew P. Galescu, Ovidiu A. Courville, Amber B. Olsen, Cara Chen, Kong Y. Stice, Eric Tanofsky-Kraff, Marian Yanovski, Jack A. TI A Randomized Controlled Trial to Prevent Depression and Ameliorate Insulin Resistance in Adolescent Girls at Risk for Type 2 Diabetes SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article DE Adolescence; Depression; Insulin resistance; Type 2 diabetes; Randomized controlled trial ID EXCESS WEIGHT-GAIN; BETA-CELL FUNCTION; CARDIORESPIRATORY FITNESS; RECIPROCAL RELATIONS; SENSITIVITY INDEXES; FEMALE ADOLESCENTS; OBESE ADOLESCENTS; HISPANIC CHILDREN; PLASMA-GLUCOSE; EFFICACY TRIAL AB Prospective data suggest depressive symptoms worsen insulin resistance and accelerate type 2 diabetes (T2D) onset. We sought to determine whether reducing depressive symptoms in overweight/obese adolescents at risk for T2D would increase insulin sensitivity and mitigate T2D risk. We conducted a parallel-group, randomized controlled trial comparing a 6-week cognitive-behavioral (CB) depression prevention group with a 6-week health education (HE) control group in 119 overweight/obese adolescent girls with mild-to-moderate depressive symptoms (Center for Epidemiological Studies-Depression Scale [CES-D] aeyen16) and T2D family history. Primary outcomes were baseline to post-intervention changes in CES-D and whole body insulin sensitivity index (WBISI), derived from 2-h oral glucose tolerance tests. Outcome changes were compared between groups using ANCOVA, adjusting for respective baseline outcome, puberty, race, facilitator, T2D family history degree, baseline age, adiposity, and adiposity change. Multiple imputation was used for missing data. Depressive symptoms decreased (p < 0.001) in CB and HE from baseline to posttreatment, but did not differ between groups (Delta CESD = -12 vs. -11, 95 % CI difference = -4 to +1, p = 0.31). Insulin sensitivity was stable (p > 0.29) in CB and HE (Delta WBISI = 0.1 vs. 0.2, 95 % CI difference = -0.6 to +0.4, p = 0.63). Among all participants, reductions in depressive symptoms were associated with improvements in insulin sensitivity (p = 0.02). Girls at risk for T2D displayed reduced depressive symptoms following 6 weeks of CB or HE. Decreases in depressive symptoms related to improvements in insulin sensitivity. Longer-term follow-up is needed to determine whether either program causes sustained decreases in depressive symptoms and improvements in insulin sensitivity. The trial was registered with clinicaltrials.gov (NCT01425905). C1 [Shomaker, Lauren B.; Kelly, Nichole R.; Pickworth, Courtney K.; Cassidy, Omni L.; Radin, Rachel M.; Shank, Lisa M.; Vannucci, Anna; Thompson, Katherine A.; Armaiz-Flores, Sara A.; Brady, Sheila M.; Demidowich, Andrew P.; Galescu, Ovidiu A.; Courville, Amber B.; Olsen, Cara; Tanofsky-Kraff, Marian; Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, NIH, Hatfield Clin Res Ctr, 10 Ctr Dr,Bldg 10,Room 1-3330,MSC 1103, Bethesda, MD 20892 USA. [Shomaker, Lauren B.; Kelly, Nichole R.; Cassidy, Omni L.; Radin, Rachel M.; Shank, Lisa M.; Vannucci, Anna; Tanofsky-Kraff, Marian] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. [Shomaker, Lauren B.; Kelly, Nichole R.] Colorado State Univ, Dept Human Dev & Family Studies, 303A Behav Sci Bldg,410 Pitkin St, Ft Collins, CO 80523 USA. [Courville, Amber B.] NIH, Dept Nutr, Mark O Hatfield Clin Ctr, Bldg 10, Bethesda, MD 20892 USA. [Olsen, Cara] Uniformed Serv Univ Hlth Sci, Dept Prevent Med, Biostat, Bethesda, MD 20814 USA. [Chen, Kong Y.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. [Stice, Eric] Oregon Res Inst, Eugene, OR 97403 USA. RP Shomaker, LB; Tanofsky-Kraff, M; Yanovski, JA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, NIH, Hatfield Clin Res Ctr, 10 Ctr Dr,Bldg 10,Room 1-3330,MSC 1103, Bethesda, MD 20892 USA.; Shomaker, LB; Tanofsky-Kraff, M (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.; Shomaker, LB (reprint author), Colorado State Univ, Dept Human Dev & Family Studies, 303A Behav Sci Bldg,410 Pitkin St, Ft Collins, CO 80523 USA. EM lauren.shomaker@colostate.edu; marian.tanofsky-kraff@usuhs.edu; jy15i@nih.gov OI Chen, Kong/0000-0002-0306-1904; Shank, Lisa/0000-0002-6922-7946 FU Intramural NIH HHS [Z01 HD000641-12, Z01 HD000641-13, Z99 HD999999, ZIA HD000641-21]; NICHD NIH HHS [R00 HD069516, K99 HD069516, ZIA HD000641] NR 48 TC 0 Z9 0 U1 11 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD OCT PY 2016 VL 50 IS 5 BP 762 EP 774 DI 10.1007/s12160-016-9801-0 PG 13 WC Psychology, Multidisciplinary SC Psychology GA DY5ZI UT WOS:000385184000013 PM 27333897 ER PT J AU Deligiannidis, KM Kroll-Desrosiers, AR Svenson, A Jaitly, N Barton, BA Hall, JE Rothschild, AJ AF Deligiannidis, Kristina M. Kroll-Desrosiers, Aimee R. Svenson, Abby Jaitly, Nina Barton, Bruce A. Hall, Janet E. Rothschild, Anthony J. TI Cortisol response to the Trier Social Stress Test in pregnant women at risk for postpartum depression SO ARCHIVES OF WOMENS MENTAL HEALTH LA English DT Article DE Postpartum; Cortisol; Depression; Anxiety ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; POSTNATAL DEPRESSION; SALIVARY CORTISOL; PSYCHOSOCIAL STRESS; AWAKENING RESPONSE; MATERNAL CORTISOL; PHYSICAL ABUSE; REACTIVITY; SYMPTOMS AB Antepartum depression and anxiety are risk factors for postpartum depression (PPD). Postpartum abnormalities in hypothalamic-pituitary-adrenal (HPA) reactivity are associated with PPD. It is not known if antepartum HPA abnormalities exist in women at risk for PPD (AR-PPD). We measured salivary cortisol response to the Trier Social Stress Test (TSST) in 44 (24 AR-PPD, 20 healthy comparison) pregnant women. Depression and anxiety were measured using the Edinburgh Postnatal Depression Scale (EPDS) and Spielberger State-Trait Anxiety Inventory-State (STAI-S). We analyzed longitudinal changes in cortisol using generalized estimating equation methods to control for the correlation within subjects at the six TSST time points. Group differences in area under the curve (AUC) were examined. A majority (70.8 %) of the AR-PPD had prior depression. EPDS total score was higher in AR-PPD vs. comparison women (mean EPDS = 9.8 +/- 4.9 vs. mean EPDS = 2.4 +/- 2.0 respectively, p < 0.001). Mean STAI-S total score was higher in AR-PPD vs. comparison women at all TSST time points and over time (z = 2.71, df = 1, p = 0.007). There was no significant difference in cortisol concentration over time between groups. We observed no detectable difference in cortisol response to psychosocial stress induced by the TSST despite clinically significant between-group differences in current/past depression and current symptomatology. C1 [Deligiannidis, Kristina M.; Svenson, Abby; Jaitly, Nina; Rothschild, Anthony J.] Univ Massachusetts, Sch Med, Ctr Psychopharmacol Res & Treatment, Dept Psychiat, Worcester, MA 01605 USA. [Deligiannidis, Kristina M.] Univ Massachusetts, Dept Psychiat, Womens Mental Hlth Program, Med Sch,UMass Mem Med Ctr, 55 Lake Ave North, Worcester, MA 01605 USA. [Deligiannidis, Kristina M.] Univ Massachusetts, Dept Obstet & Gynecol, Womens Mental Hlth Program, Med Sch,UMass Mem Med Ctr, 55 Lake Ave North, Worcester, MA 01605 USA. [Kroll-Desrosiers, Aimee R.; Barton, Bruce A.] Univ Massachusetts, Dept Quantitat Hlth Sci, Sch Med, Worcester, MA 01605 USA. [Jaitly, Nina; Hall, Janet E.] NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. [Hall, Janet E.] Harvard Med Sch, Reprod Endocrine Unit, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Deligiannidis, KM (reprint author), Univ Massachusetts, Sch Med, Ctr Psychopharmacol Res & Treatment, Dept Psychiat, Worcester, MA 01605 USA.; Deligiannidis, KM (reprint author), Univ Massachusetts, Dept Psychiat, Womens Mental Hlth Program, Med Sch,UMass Mem Med Ctr, 55 Lake Ave North, Worcester, MA 01605 USA.; Deligiannidis, KM (reprint author), Univ Massachusetts, Dept Obstet & Gynecol, Womens Mental Hlth Program, Med Sch,UMass Mem Med Ctr, 55 Lake Ave North, Worcester, MA 01605 USA. EM Kristina.Deligiannidis@umassmemorial.org; aimee.kroll@umassmed.edu; abbysve@gmail.com; nina.jaitly@nih.gov; bruce.barton@umassmed.edu; janet.hall@nih.gov; anthony.rothschild@umassmemorial.org OI Deligiannidis, Kristina/0000-0001-7439-2236; Barton, Bruce/0000-0001-7878-8895; Hall, Janet/0000-0003-4644-3061 FU National Center for Advancing Translational Sciences, National Institutes of Health [UL1 TR000161]; National Institutes of Health [5K23MH097794] FX This study was supported by the National Center for Advancing Translational Sciences, National Institutes of Health Grant (UL1 TR000161), and National Institutes of Health Grant (5K23MH097794) awarded to Dr. Deligiannidis. The sponsoring agency had no further role in the study design and analysis, the writing of the report, or the decision to submit the paper for publication. The authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. The views expressed in this article are those of the authors and do not necessarily reflect the position of the NIH. NR 58 TC 0 Z9 0 U1 5 U2 5 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 1434-1816 EI 1435-1102 J9 ARCH WOMEN MENT HLTH JI Arch. Womens Ment. Health PD OCT PY 2016 VL 19 IS 5 BP 789 EP 797 DI 10.1007/s00737-016-0615-7 PG 9 WC Psychiatry SC Psychiatry GA DW4JW UT WOS:000383610000008 PM 26951216 ER PT J AU Musset, L Allenbach, Y Benveniste, O Boyer, O Bossuyt, X Bentow, C Phillips, J Mammen, A Van Damme, P Westhovens, R Ghirardello, A Doria, A Choi, MY Fritzler, MJ Schmeling, H Muro, Y Garcia-De la Torre, I Ortiz-Villalvazo, MA Bizzaro, N Infantino, M Imbastaro, T Peng, QL Wang, GC Vencovsky, J Klein, M Krystufkova, O Franceschini, F Fredi, M Hue, S Belmondo, T Danko, K Mahler, M AF Musset, Lucile Allenbach, Yves Benveniste, Olivier Boyer, Olivier Bossuyt, Xavier Bentow, Chelsea Phillips, Joe Mammen, Andrew Van Damme, Philip Westhovens, Rene Ghirardello, Anna Doria, Andrea Choi, May Y. Fritzler, Marvin J. Schmeling, Heinrike Muro, Yoshinao Garcia-De la Torre, Ignacio Ortiz-Villalvazo, Miguel A. Bizzaro, Nicola Infantino, Maria Imbastaro, Tiziana Peng, Qinglin Wang, Guochun Vencovsky, Jiri Klein, Martin Krystufkova, Olga Franceschini, Franco Fredi, Micaela Hue, Sophie Belmondo, Thibaut Danko, Katalin Mahler, Michael TI Anti-HMGCR antibodies as a biomarker for immune-mediated necrotizing myopathies: A history of statins and experience from a large international multi-center study SO AUTOIMMUNITY REVIEWS LA English DT Review DE Autoimmune myositis; Autoantibodies; Immune-mediated necrotizing myopathy; HMGCR; Statins ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; IDIOPATHIC INFLAMMATORY MYOPATHIES; CLASSIFICATION CRITERIA; AUTOIMMUNE MYOPATHY; AMERICAN-COLLEGE; RHEUMATOLOGY/EUROPEAN LEAGUE; REDUCTASE AUTOANTIBODIES; RISK-ASSESSMENT; MYOSITIS; DIAGNOSIS AB In an effort to find naturally occurring substances that reduce cholesterol by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), statins were first discovered by Endo in 1972. With the widespread prescription and use of statins to decrease morbidity from myocardial infarction and stroke, it was noted that approximately 5% of all statin users experienced muscle pain and weakness during treatment In a smaller proportion of patients, the myopathy progressed to severe morbidity marked by proximal weakness and severe muscle wasting. Remarkably, Mammen and colleagues were the first to discover that the molecular target of statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), is an autoantibody target in patients that develop an immune-mediated necrotizing myopathy (IMNM). These observations have been confirmed in a number of studies but, until today, a multi-center, international study of IMNM, related idiopathic inflammatory myopathies (IIM), other auto-inflammatory conditions and controls has not been published. Accordingly, an international, multi-center study investigated the utility of anti-HMGCR antibodies in the diagnosis of statin-associated IMNM in comparison to different forms of IIM and controls. This study included samples from patients with different forms of IIM (n = 1250) and patients with other diseases (n = 656) that were collected from twelve sites and tested for anti-HMGCR antibodies by ELISA. This study confirmed that anti-HMGCR autoantibodies, when found in conjunction with statin use, characterize a subset of IIM who are older and have necrosis on muscle biopsy. Taken together, the data to date indicates that testing for anti-HMGCR antibodies is important in the differential diagnosis of IIM and might be considered for future classification criteria. (C) 2016 Published by Elsevier B.V. C1 [Musset, Lucile] Pitie Salpetriere Univ Hosp Paris, AP HP, Dept Immunol, Immunochem & Autoimmun Lab, Paris, France. [Allenbach, Yves; Benveniste, Olivier] Pitie Salpetriere Univ Hosp, AP HP, Dept Internal Med & Clin Immunol, Hosp Univ Dept Inflammat Immunopathol & Biotherap, Paris, France. [Allenbach, Yves; Benveniste, Olivier] Univ Paris 06, Sorbonne Univ, INSERM, U974, Paris, France. [Boyer, Olivier] Rouen Univ Hosp, Dept Immunol, Rouen, France. [Boyer, Olivier] INSERM, U905, Rouen, France. [Boyer, Olivier] Normandie Univ, IRIB, Rouen, France. [Bossuyt, Xavier] Univ Hosp Leuven, Dept Lab Med, Leuven, Belgium. [Bossuyt, Xavier] Katholieke Univ Leuven, Dept Microbiol & Immunol, Leuven, Belgium. [Bentow, Chelsea; Phillips, Joe; Mahler, Michael] Inova Diagnost, Dept Res, San Diego, CA USA. [Mammen, Andrew] NIAMSD, NIH, Bethesda, MD 20892 USA. [Van Damme, Philip] Univ Leuven, KU Leuven, Dept Neurosci, VIB Vesalius Res Ctr,Expt Neurol Lab Neurobiol, Leuven, Belgium. [Van Damme, Philip] Univ Hosp Leuven, Dept Neurol, Leuven, Belgium. [Westhovens, Rene] Katholieke Univ Leuven, Skeletal Biol & Engn Res Ctr, Dept Dev & Regenerat, Leuven, Belgium. [Westhovens, Rene] Univ Hosp Leuven, Rheumatol, Leuven, Belgium. [Ghirardello, Anna; Doria, Andrea] Univ Padua, Dept Med, Div Rheumatol, Padua, Italy. [Choi, May Y.; Fritzler, Marvin J.] Univ Calgary, Dept Med, Calgary, AB, Canada. [Schmeling, Heinrike] Univ Calgary, Dept Pediat, Alberta Childrens Hosp, Calgary, AB, Canada. [Muro, Yoshinao] Nagoya Univ, Div Connect Tissue Dis & Autoimmun, Dept Dermatol, Grad Sch Med, Nagoya, Aichi, Japan. [Garcia-De la Torre, Ignacio] Hosp Gen Occidente Seguro Social, Dept Immunol & Rheumatol, Zapopan, Jalisco, Mexico. [Garcia-De la Torre, Ignacio] Univ Guadalajara, Zapopan, Jalisco, Mexico. [Ortiz-Villalvazo, Miguel A.] Hosp Civil Dr Juan I Menchaca, Dept Internal Med, Guadalajara, Jalisco, Mexico. [Bizzaro, Nicola] San Antonio Hosp, Clin Pathol Lab, Tolmezzo, Italy. [Infantino, Maria] S Giovanni di Dio Hosp, Lab Immunol & Allergol, Florence, Italy. [Imbastaro, Tiziana] Lab Autoimmune Dis Diagnost, PO Spirit Santo, Pescara, Italy. [Peng, Qinglin; Wang, Guochun] China Japan Friendship Hosp, Dept Rheumatol, Beijing, Peoples R China. [Vencovsky, Jiri; Klein, Martin; Krystufkova, Olga] Charles Univ Prague, Inst Rheumatol, Prague, Czech Republic. [Vencovsky, Jiri; Klein, Martin; Krystufkova, Olga] Charles Univ Prague, Dept Rheumatol, Prague, Czech Republic. [Franceschini, Franco; Fredi, Micaela] Univ Brescia, Rheumatol & Clin Immunol, Spedali Civili Brescia, I-25121 Brescia, Italy. [Franceschini, Franco; Fredi, Micaela] Univ Pavia, I-27100 Pavia, Italy. [Hue, Sophie; Belmondo, Thibaut] Henri Mondor Univ Hosp, Dept Immunohematol, Creteil, France. [Danko, Katalin] Univ Debrecen, Div Immunol, Dept Internal Med 3, Med & Hlth Sci Ctr, Debrecen, Hungary. RP Mahler, M (reprint author), Inova Diagnost, 9900 Old Grove Rd, San Diego, CA 92131 USA. EM mmahler@inovadx.com RI Van Damme, Philip/A-6464-2009 OI Van Damme, Philip/0000-0001-6384-0611 FU Ministry of Health [00023728] FX The work of Jiri Vencovsky in myositis is supported by project from Ministry of Health No. 00023728. We acknowledge Laurent Drouot and Fabienne Jouen (Rouen University Hospital, Department of Immunology, Rouen, France) as well as Jean-Luc Charuel and Laurent Dufat (Pitie-Salpetriere Hospital University, Paris, France) for their help during the study. We acknowledge Lisa Christopher-Stine for proofreading the draft manuscript and providing valuable suggestions. The local ethics committees who approved the study for the various centers involved included the local ethics committee of the University Hospital Leuven (ML9544, Leuven, Belgium), the local ethics committee of CPP-Ile-de-France VI GH Pitie-Salpetriere/Ch Foix (President: Dr Laurent Capelle, Paris, France), the Italian Local Ethics Committee (Comitato Etico per la Sperimentazione dell'Azienda Ospedaliera di Padova, Prot. N. 2542P), the Conjoint Health Research Ethics Board (CHREB) of the University of Calgary (Calgary, Canada), the local ethics committees of the Nagoya University Graduate School of Medicine (Nagoya, Japan), the Human Ethics Board of China-Japan Friendship Hospital (Beijing, China), and the local ethics committee at the Institute of Rheumatology (Prague, Czech Republic). Where no ethics committee was required per institution guidelines, informed consent was obtained from the patients involved in the study. NR 72 TC 1 Z9 2 U1 9 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-9972 EI 1873-0183 J9 AUTOIMMUN REV JI Autoimmun. Rev. PD OCT PY 2016 VL 15 IS 10 BP 983 EP 993 DI 10.1016/j.autrev.2016.07.023 PG 11 WC Immunology SC Immunology GA DY1RM UT WOS:000384872100009 PM 27491568 ER PT J AU Alousi, AM Anasetti, C Antin, JH Appelbaum, FR Bashey, A Confer, DL Devine, SM DiFronzo, N Giralt, SA Grupp, SN Hari, PN Heslop, HE Horowitz, MM Jones, RJ Kurtzberg, J Lazarus, HM Lowsky, R Mendizabal, AM Merritt, W Nakamura, R Pulsipher, MA Ratanatharathorn, V Stadtmauer, EA Stiff, PJ Vose, JM Weisdorf, DJ Westervelt, P Wingard, JR Yanik, GA AF Alousi, Amin M. Anasetti, Claudio Antin, Joseph H. Appelbaum, Frederick R. Bashey, Asad Confer, Dennis L. Devine, Steven M. DiFronzo, Nancy Giralt, Sergio A. Grupp, Stephan N. Hari, Parameswaran N. Heslop, Helen E. Horowitz, Mary M. Jones, Richard J. Kurtzberg, Joanne Lazarus, Hillard M. Lowsky, Robert Mendizabal, Adam M. Merritt, William Nakamura, Ryotaro Pulsipher, Michael A. Ratanatharathorn, Voravit Stadtmauer, Edward A. Stiff, Patrick J. Vose, Julie M. Weisdorf, Daniel J. Westervelt, Peter Wingard, John R. Yanik, Gregory A. CA Blood Marrow Transplant Clinical TI The Blood and Marrow Transplant Clinical Trials Network: An Effective Infrastructure for Addressing Important Issues in Hematopoietic Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE Hematopoietic cell transplantation; Blood and Marrow Transplant; Clinical Trials Network; Infrastructure; Review ID VERSUS-HOST-DISEASE; UMBILICAL-CORD BLOOD; COST-EFFECTIVENESS ANALYSIS; COOPERATIVE-ONCOLOGY-GROUP; INVASIVE FUNGAL-INFECTION; ACUTE MYELOID-LEUKEMIA; SCIENCE SYMPOSIUM 2007; BMT CTN 0902; BONE-MARROW; MULTIPLE-MYELOMA AB Hematopoietic cell transplantation (HCT) is a rapidly evolving field with active preclinical and clinical development of new strategies for patient assessment, graft selection and manipulation, and pre- and post transplantation drug and cell therapy. New strategies require evaluation in definitive clinical trials; however, HCT trials face unique challenges, including the relatively small number of transplantations performed at any single center, the diverse indications for HCT requiring dissimilar approaches, the complex nature of the intervention itself, the risk of multiple complications in the immediate post-transplantation period, and the risk of important, though infrequent, late effects. The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) was established by the US National Heart Lung and Blood Institute and the National Cancer Institute to meet these challenges. In its 15 years as a network, the BMT CTN has proven to be a successful infrastructure for planning, implementing, and completing such trials and for providing definitive answers to questions leading to improvements in the understanding and practice of HCT. It has opened 37 trials, about one-half phase 2 and one-half phase 3, enrolled more than 8000 patients, and published 57 papers addressing important issues in the treatment of patients with life-threatening malignant and nonmalignant blood disorders. This review describes the network's accomplishments, key components of its success, lessons learned over the past 15 years, and challenges for the future. (C) 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. C1 [Blood Marrow Transplant Clinical] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Alousi, Amin M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Anasetti, Claudio] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Appelbaum, Frederick R.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Bashey, Asad] Northside Hosp, Blood & Marrow Transplant Program, Atlanta, GA USA. [Confer, Dennis L.] Natl Marrow Donor Program, Minneapolis, MN USA. [Devine, Steven M.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [DiFronzo, Nancy] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. [Giralt, Sergio A.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Grupp, Stephan N.; Horowitz, Mary M.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Hari, Parameswaran N.; Horowitz, Mary M.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Heslop, Helen E.] Baylor Coll Med, Houston, TX 77030 USA. [Jones, Richard J.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Kurtzberg, Joanne] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Lazarus, Hillard M.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Lowsky, Robert] Stanford Hosp & Clin, Palo Alto, CA USA. [Mendizabal, Adam M.] Emmes Corp, Rockville, MD USA. [Merritt, William] NCI, NIH, Bethesda, MD 20892 USA. [Nakamura, Ryotaro] City Hope Natl Med Ctr, 1500 E Duarte Rd, Duarte, CA 91010 USA. [Pulsipher, Michael A.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Ratanatharathorn, Voravit] Karmanos Canc Inst, Detroit, MI USA. [Stadtmauer, Edward A.] Univ Penn, Philadelphia, PA 19104 USA. [Stiff, Patrick J.] Loyola Univ, Med Ctr, 2160 S 1st Ave, Maywood, IL 60153 USA. [Vose, Julie M.] Univ Nebraska Med Ctr, Omaha, NE USA. [Weisdorf, Daniel J.] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Westervelt, Peter] Washington Univ, St Louis, MO USA. [Wingard, John R.] Univ Florida, Gainesville, FL USA. [Yanik, Gregory A.] Univ Michigan, Ann Arbor, MI 48109 USA. RP Horowitz, MM (reprint author), Med Coll Wisconsin, Milwaukee, WI 53226 USA. FU National Institutes of Health; Health Resources and Services Administration FX This work was supported by the National Institutes of Health and the Health Resources and Services Administration. The views expressed do not necessarily represent the views of the National Institutes of Health, the Health Resources and Services Administration, or the United States government. NR 68 TC 0 Z9 0 U1 4 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD OCT PY 2016 VL 22 IS 10 BP 1747 EP 1757 DI 10.1016/j.bbmt.2016.07.003 PG 11 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA DY3BG UT WOS:000384965200004 ER PT J AU Khan, NE Rosenberg, PS Alter, BP AF Khan, Nicholas E. Rosenberg, Philip S. Alter, Blanche P. TI Preemptive Bone Marrow Transplantation and Event-Free Survival in Fanconi Anemia SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Preemptive transplantation; Fanconi anemia; Markov model; Decision analysis ID STEM-CELL TRANSPLANTATION; DIAMOND-BLACKFAN ANEMIA; DECISION-MAKING; FAILURE SYNDROMES; CANCER; REGISTRY AB Fanconi anemia (FA) is a rare inherited bone marrow failure syndrome associated with high risks of severe bone marrow failure (BMF), acute myeloid leukemia (AML), and solid tumors (ST). Bone marrow transplantation (BMT) provides a theoretical cure for hematologic risks (BMF, AML), but it introduces uncertain risks of transplantation-related mortality (TRM) and carcinogenicity. We developed a mathematical (Markov) decision model to estimate event-free survival (EFS) conditional on age based on per-year cause-specific hazard rates. We assumed that preemptive (PE) BMT eliminates the risks of BMF and AML, but it may introduce independent risks of TRM or influence the trajectory to ST. Our model suggested that the expected mean EFS in FA is higher for PE-BMT at young ages, with minimal risk of TRM and with little carcinogenicity. PE-BMT in adults decreased expected EFS because of the greater competing risk of ST in adulthood. Estimates of EFS conditioned on attained age may be used in shared decision-making when clinicians must counsel patients using limited data. Our methods may be used to model early transplantation in other blood disorders for which hematopoietic stem cell transplantation mitigates some but not all of the risks. Published by Elsevier Inc. on behalf of the American Society for Blood and Marrow Transplantation. C1 [Khan, Nicholas E.; Alter, Blanche P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 6E452, Bethesda, MD 20850 USA. [Rosenberg, Philip S.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Alter, BP (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 6E452, Bethesda, MD 20850 USA. EM alterb@mail.nih.gov FU Intramural Research Program of the National Cancer Institute of the National Institutes of Health FX This research was supported in part by the Intramural Research Program of the National Cancer Institute of the National Institutes of Health. NR 23 TC 1 Z9 1 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD OCT PY 2016 VL 22 IS 10 BP 1888 EP 1892 DI 10.1016/j.bbmt.2016.06.018 PG 5 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA DY3BG UT WOS:000384965200022 PM 27345141 ER PT J AU Doyle, M Pohost, GM Merz, CNB Shaw, LJ Sopko, G Rogers, WJ Sharaf, BL Pepine, CJ Thompson, DV Rayarao, G Tauxe, L Kelsey, SF Biederman, RWW AF Doyle, Mark Pohost, Gerald M. Merz, C. Noel Bairey Shaw, Leslee J. Sopko, George Rogers, William J. Sharaf, Barry L. Pepine, Carl J. Thompson, Diane V. Rayarao, Geetha Tauxe, Lindsey Kelsey, Sheryl F. Biederman, Robert W. W. TI Use of bio-informatics assessment schema (BIAS) to improve diagnosis and prognosis of myocardial perfusion data: results from the NHLBI-sponsored women's ischemia syndrome evaluation (WISE) SO CARDIOVASCULAR DIAGNOSIS AND THERAPY LA English DT Article DE Modeling; prognosis; diagnosis; myocardial perfusion imaging (MPI); women ID CARDIOVASCULAR MAGNETIC-RESONANCE; CORONARY-ARTERY-DISEASE; FEASIBILITY; RESERVE; SPECT; FLOW AB Background: We introduce an algorithmic approach to optimize diagnostic and prognostic value of gated cardiac single photon emission computed tomography (SPECT) and magnetic resonance (MR) myocardial perfusion imaging (MPI) modalities in women with suspected myocardial ischemia. The novel approach: bioinformatics assessment schema (BIAS) forms a mathematical model utilizing MPI data and cardiac metrics generated by one modality to predict the MPI status of another modality. The model identifies cardiac features that either enhance or mask the image-based evidence of ischemia. For each patient, the BIAS model value is used to set an appropriate threshold for the detection of ischemia. Methods: Women (n=130), with symptoms and signs of suspected myocardial ischemia, underwent MPI assessment for regional perfusion defects using two different modalities: gated SPECT and MR. To determine perfusion status, MR data were evaluated qualitatively (MRIQL) and semi-quantitatively (MRISQ) while SPECT data were evaluated using conventional clinical criteria. Evaluators were masked to results of the alternate modality. These MPI status readings were designated "original". Two regression models designated "BIAS" models were generated to model MPI status obtained with one modality (e.g., MRI) compared with a second modality (e.g., SPECT), but importantly, the BIAS models did not include the primary Original MPI reading of the predicting modality. Instead, the BIAS models included auxiliary measurements like left ventricular chamber volumes and myocardial wall thickness. For each modality, the BIAS model was used to set a progressive threshold for interpretation of MPI status. Women were then followed for 38 +/- 14 months for the development of a first major adverse cardiovascular event [MACE: CV death, nonfatal myocardial infarction (MI) or hospitalization for heart failure]. Original and BIAS-augmented perfusion status were compared in their ability to detect coronary artery disease (CAD) and for prediction of MACE. Results: Adverse events occurred in 14 (11%) women and CAD was present in 13 (10%). There was a positive correlation of maximum coronary artery stenosis and BIAS score for MRI and SPECT (P<0.001). Receiver operator characteristic (ROC) analysis was conducted and showed an increase in the area under the curve of the BIAS-augmented MPI interpretation of MACE vs. the original for MRISQ (0.78 vs. 0.54), MRIQL (0.78 vs. 0.64), SPECT (0.82 vs. 0.63) and the average of the three readings (0.80 +/- 0.02 vs. 0.60 +/- 0.05, P<0.05). Conclusions: Increasing values of the BIAS score generated by both MRI and SPECT corresponded to the increasing prevalence of CAD and MACE. The BIAS-augmented detection of ischemia better predicted MACE compared with the Original reading for the MPI data for both MRI and SPECT. C1 [Doyle, Mark; Thompson, Diane V.; Rayarao, Geetha; Biederman, Robert W. W.] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. [Pohost, Gerald M.] Univ Southern Calif, Keck Med Ctr, Los Angeles, CA USA. [Merz, C. Noel Bairey; Shaw, Leslee J.] Cedars Sinai Heart Inst, Barbra Streisand Womens Heart Ctr, Los Angeles, CA USA. [Sopko, George] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. [Rogers, William J.; Tauxe, Lindsey] Univ Alabama Birmingham, Birmingham, AL USA. [Sharaf, Barry L.] Brown Univ, Providence, RI 02912 USA. [Pepine, Carl J.] Univ Florida, Gainesville, FL USA. [Kelsey, Sheryl F.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. RP Doyle, M (reprint author), Allegheny Gen Hosp, Div Cardiol, CV MRI Ctr, 320 East North Ave, Pittsburgh, PA 15212 USA. EM mdoyle@wpahs.org FU NHLBI NIH HHS [N01 HV068161, N01 HV068164, N01HV68162, N01HV68163, R01 HL073412] NR 16 TC 0 Z9 0 U1 2 U2 2 PU AME PUBL CO PI SHEUNG WAN PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG 00000, PEOPLES R CHINA SN 2223-3652 EI 2223-3660 J9 CARDIOVASC DIAGN THE JI Cardiovisc. Diagn. Ther. PD OCT PY 2016 VL 6 IS 5 BP 424 EP U9 DI 10.21037/cdt.2016.03.11 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DX6KS UT WOS:000384493200003 PM 27747165 ER PT J AU Morkl, S Muller, NJ Blesl, C Wilkinson, L Tmava, A Wurm, W Holl, AK Painold, A AF Moerkl, Sabrina Mueller, Nicole J. Blesl, Claudia Wilkinson, Leonora Tmava, Adelina Wurm, Walter Holl, Anna K. Painold, Annamaria TI Problem solving, impulse control and planning in patients with early- and late-stage Huntington's disease SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE LA English DT Article DE Huntington's disease; Executive function; Tower of London; Neuropsychology; Disease severity ID DECISION-MAKING; LONDON TASK; SCHIZOPHRENIA; COMPENSATION; PROGRESSION; DIAGNOSIS; PATHOLOGY; MEMORY; TOWER; HD AB Sub-domains of executive functions, including problems with planning, accuracy, impulsivity, and inhibition, are core features of Huntington's disease. It is known that the decline of cognitive function in Huntington's disease is related to the anatomical progression of pathology in the basal ganglia. However, it remains to be determined whether the severity of executive dysfunction depends on the stage of the disease. To examine the severity of sub-domains of executive dysfunction in early- and late-stage Huntington's disease, we studied performance in the Tower of London task of two groups of Huntington's disease patients (Group 1: early, n = 23, and Group 2: late stage, n = 29), as well as a third group of age, education, and IQ matched healthy controls (n = 34). During the task, we measured the total number of problems solved, total planning time, and total number of breaks taken. One aspect of executive function indexed by the number of solved problems seems to progress in the course of the disease. Late-stage Huntington's disease patients scored significantly worse than early-stage patients and controls, and early-stage patients scored significantly worse than controls on this measure of accuracy. In contrast, late- and early-stage HD patients did not differ in terms of planning time and number of breaks. Early- and late-stage HD pathology has a different impact on executive sub-domains. While accuracy differs between early- and late-stage HD patients, other domains like planning time and number of breaks do not. Striatal degeneration, which is a characteristic feature of the disease, might not affect all aspects of executive function in HD. C1 [Moerkl, Sabrina; Mueller, Nicole J.; Blesl, Claudia; Tmava, Adelina; Wurm, Walter; Holl, Anna K.; Painold, Annamaria] Med Univ Graz, Dept Psychiat, Auenbruggerpl 31-1, A-8036 Graz, Austria. [Wilkinson, Leonora] NINDS, Behav Neurol Unit, NIH, 10 Ctr Dr,MSC 1440, Bethesda, MD 20892 USA. RP Blesl, C (reprint author), Med Univ Graz, Dept Psychiat, Auenbruggerpl 31-1, A-8036 Graz, Austria. EM claudia.blesl@medunigraz.at FU Medical University of Graz FX Open access funding provided by Medical University of Graz. We express our kind appreciation to all the participants of the study. NR 36 TC 0 Z9 0 U1 8 U2 8 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0940-1334 EI 1433-8491 J9 EUR ARCH PSY CLIN N JI Eur. Arch. Psych. Clin. Neurosci. PD OCT PY 2016 VL 266 IS 7 BP 663 EP 671 DI 10.1007/s00406-016-0707-4 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA DY5TY UT WOS:000385167700009 PM 27372072 ER PT J AU Li, DX Ferrada, MA Avdic, E Tamma, PD Cosgrove, SE AF Li, David X. Ferrada, Marcela A. Avdic, Edina Tamma, Pranita D. Cosgrove, Sara E. TI Sustained Impact of an Antibiotic Stewardship Intervention for Community-Acquired Pneumonia SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID IMPLEMENTATION AB Antibiotic stewardship interventions targeting community-acquired pneumonia have been successful in reducing antibiotic overuse in the short term, but the sustainability of their effects has not been investigated. We report that improvements in antibiotic use due to a syndrome-focused intervention for community-acquired pneumonia were sustained 3 years later without additional intervention. C1 [Li, David X.; Ferrada, Marcela A.; Cosgrove, Sara E.] Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. [Ferrada, Marcela A.] NIH, Dept Crit Care Med, Bldg 10, Bethesda, MD 20892 USA. [Avdic, Edina] Johns Hopkins Univ Hosp, Dept Pharm, Baltimore, MD 21287 USA. [Tamma, Pranita D.] Johns Hopkins Univ, Sch Med, Div Pediat Infect Dis, Baltimore, MD USA. RP Cosgrove, SE (reprint author), Johns Hopkins Univ Hosp, 600 N Wolfe St,Halsted 827, Baltimore, MD 21287 USA. EM scosgro1@jhmi.edu FU Pfizer Grants for Learning and Change; Joint Commission FX Pfizer Grants for Learning and Change and the Joint Commission (grant to P.D.T., E.A., and S.E.C.). NR 9 TC 0 Z9 0 U1 2 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD OCT PY 2016 VL 37 IS 10 BP 1243 EP 1246 DI 10.1017/ice.2016.165 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA DY4GS UT WOS:000385057600016 PM 27498601 ER PT J AU Sy, AA Kim, WS Chen, J Shen, Y Tao, C Lee, JS AF Sy, A. A. Kim, W. S. Chen, J. Shen, Y. Tao, C. Lee, J. S. TI Acculturation levels and personalizing orthognathic surgery for the Asian American patient SO INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article DE facial aesthetics; ethnic variation; Suinn-Lew survey; Western aesthetics; customized orthognathic treatment planning ID HEALTH-CARE; ATTRACTIVENESS; QUALITY AB This study was performed to investigate whether the level of acculturation among Asians living in the USA plays a significant role in their opinion of facial profiles. One hundred and ninety-eight Asian American subjects were asked to complete a pre-validated survey to measure their level of acculturation and to evaluate four sets of pictures that displayed a class II male, class II female, class III male, and class III female. Each set consisted of three lateral profile pictures: an initial unaltered photo, a picture simulating a flatter profile (orthodontic camouflage in class II; mandibular setback in class III), and a picture simulating a fuller profile (mandibular advancement in class II; maxillary advancement in class III). For the class II male, subjects who were more acculturated indicated that a flatter profile (orthodontic camouflage) was less attractive. For the class II female, higher acculturated subjects chose expansive treatment (mandibular advancement) as more aesthetic compared to the less acculturated subjects. Each of these scenarios had statistically significant odds ratios. In general, highly acculturated subjects preferred a fuller facial profile, while low acculturated subjects preferred a flatter facial profile appearance, except for the class III female profile, which did not follow this trend. C1 [Sy, A. A.; Lee, J. S.] UCSF Oral & Maxillofacial Surg, Box 0440,521 Parnassus Ave,Clin Sci Room 522C, San Francisco, CA 94143 USA. [Kim, W. S.] Columbia Univ, Oral & Maxillofacial Surg, New York, NY USA. [Shen, Y.] Washington St, Daly City, CA USA. [Lee, J. S.] NIDCR, NIH, Bethesda, MD USA. RP Sy, AA (reprint author), UCSF Oral & Maxillofacial Surg, Box 0440,521 Parnassus Ave,Clin Sci Room 522C, San Francisco, CA 94143 USA. EM Aldrich.sy@ucsf.edu OI Kim, William/0000-0001-7693-3454 FU Oral and Maxillofacial Surgery Foundation Student Research Fund FX This research was supported by the Oral and Maxillofacial Surgery Foundation Student Research Fund. NR 26 TC 0 Z9 0 U1 3 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0901-5027 EI 1399-0020 J9 INT J ORAL MAX SURG JI Int. J. Oral Maxillofac. Surg. PD OCT PY 2016 VL 45 IS 10 BP 1201 EP 1208 DI 10.1016/j.ijom.2016.04.013 PG 8 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA DY1MB UT WOS:000384858000003 PM 27197783 ER PT J AU Yoneyama, K Donekal, S Venkatesh, BA Wu, CO Liu, CY Nacif, MS Armstrong, A Gomes, AS Hundley, WG McClelland, RL Bluemke, DA Lima, JAG AF Yoneyama, Kihei Donekal, Sirisha Venkatesh, Bharath A. Wu, Colin O. Liu, Chia-Ying Nacif, Marcelo Souto Armstrong, Anderson Gomes, Antoinette S. Hundley, W. Gregory McClelland, Robyn L. Bluemke, David A. Lima, Joao A. G. TI Natural History of Myocardial Function in an Adult Human Population Serial Longitudinal Observations From MESA SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE aging; heart failure; hypertension; left ventricular; torsion ID LEFT-VENTRICULAR HYPERTROPHY; HYPERTENSIVE HEART-DISEASE; CARDIAC MAGNETIC-RESONANCE; ASYMPTOMATIC INDIVIDUALS; CARDIOVASCULAR EVENTS; ATHEROSCLEROSIS MESA; PROGNOSTIC VALUE; BLOOD-PRESSURE; MIDDLE-AGE; DYSFUNCTION AB OBJECTIVES The aim of this longitudinal study was to define the determinants of aging-related left ventricular (LV) remodeling and function in a large multiethnic population. BACKGROUND The influence of risk factor exposure on myocardial remodeling and function in humans across adult life remains incompletely understood. MESA (Multi-Ethnic Study of Atherosclerosis) is a Longitudinal population-based cohort of asymptomatic adults at baseline. METHODS We examined 757 participants who were free of clinical cardiovascular disease and underwent tagged cardiac magnetic resonance both at baseline and at the 10-year follow-up as part of the MESA study. LV remodeling, circumferential shortening (CS), and torsion were assessed by tagged cardiac magnetic resonance. Multivariable linear regression was used to determine the association of changes in risk factors with changes in cardiac geometry and function. RESULTS The mean age of participants was 63 9 years at baseline; 50% were women. Overall, the LV mass-to volume ratio increased by 10% over 10 years (p < 0.01). CS was unchanged (17.8% to 17.9%, p = 0.246), whereas torsion increased by 13% (3.8 degrees/cm to 4.3 degrees/cm, p < 0.001). Increased systolic blood pressure was associated with reduced CS (-0.02%/mm Hg, p < 0.01). Participants who remained on antihypertensive therapy during the whole study had a greater decrease in LV mass-to-volume ratio (-0.045 vs. no medication, p < 0.05) with a greater increase in CS (0.78% vs. no medication, p < 0.01). Moreover, greater LV mass at baseline was significantly associated with reduced CS (-0.02%/g, p < 0.01) and torsion (-0.02 degrees/cm/g, p < 0.01) independently of risk factors. CONCLUSIONS Longitudinal observation demonstrates that LV mass and worsening risk factors are fundamental determinants of reduced regional myocardial shortening over 10 years. Increased torsion of the myocardial wall is seen with progressive concentric remodeling and may explain why systolic function is maintained with aging. (C) 2016 by the American College of Cardiology Foundation. C1 [Yoneyama, Kihei; Donekal, Sirisha; Venkatesh, Bharath A.; Nacif, Marcelo Souto; Armstrong, Anderson; Lima, Joao A. G.] Johns Hopkins Univ, Dept Cardiol, Baltimore, MD USA. [Yoneyama, Kihei] St Marianna Univ, Sch Med, Kawasaki, Kanagawa, Japan. [Wu, Colin O.] NHLBI, Off Biostat Res, Bldg 10, Bethesda, MD 20892 USA. [Liu, Chia-Ying; Nacif, Marcelo Souto; Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, NIH, Ctr Clin, Bethesda, MD USA. [Gomes, Antoinette S.] Univ Calif Los Angeles, Sch Med, Dept Radiol, Los Angeles, CA 90024 USA. [Hundley, W. Gregory] Wake Forest Univ Hlth Sci, Dept Internal Med Cardiol, Winston Salem, NC USA. [McClelland, Robyn L.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Lima, JAG (reprint author), Johns Hopkins Univ, Johns Hopkins Hosp, Div Cardiol, Blalock 524D1,600 North Wolfe St, Baltimore, MD 21287 USA. EM jlima@jhmi.edu OI Bluemke, David/0000-0002-8323-8086 FU National Heart, Lung, and Blood Institute [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]; National Center for Research Resources [UL1-TR-000040, UL1-TR-001079] FX This research was supported by 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, and N01-HC-95169 from the National Heart, Lung, and Blood Institute and by grants UL1-TR-000040 and UL1-TR-001079 from the National Center for Research Resources. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 37 TC 2 Z9 2 U1 1 U2 1 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 OCT PY 2016 VL 9 IS 10 BP 1164 EP 1173 DI 10.1016/j.jcmg.2016.01.038 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA DY6JO UT WOS:000385212400005 PM 27639760 ER PT J AU Lancaster, C Pristatsky, P Hoang, VM Casimiro, DR Schwartz, RM Rustandi, R Ha, S AF Lancaster, Catherine Pristatsky, Pavlo Hoang, Van M. Casimiro, Danilo R. Schwartz, Richard M. Rustandi, Richard Ha, Sha TI Characterization of N-glycosylation profiles from mammalian and insect cell derived chikungunya VLP SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE Chikungunya; Vaccine; VLP; Glycosylation; HILIC ID PARTICLE VACCINE; NEUTRALIZING ANTIBODIES; VIRAL HEMAGGLUTININ; AEDES-ALBOPICTUS; VIRUS; CULTURE; IMMUNOGENICITY; GLYCOPROTEINS; PATTERNS; MOSQUITO AB Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes severe arthralgia. The envelope of CHIKV is composed of 240 copies of two glycoproteins: El and E2. In this work, we have characterized the N-glycosylation patterns of CHIKV virus-like particles (VLP5), containing both El and E2 proteins, derived from mammalian and insect cells using hydrophilic interaction liquid chromatography (HILIC) with fluorescence (FL) and mass spectrometry (MS) detection. While HEK293 derived CHIKV VLPs contain oligomannose, hybrid and complex glycans, VLPs derived from SfBasic predominantly contain oligomannose glycans. This strong host dependence of N-glycosylation pattern resembles other alphaviruses such as SINV. The VLPs from HEK293 and SfBasic, with significantly different N-glycosylation profiles, are valuable reagents enabling future in-depth correlation studies between immunogenicity and glycosylation. In addition, the characterization tools presented here allow one to monitor glycosylation during vaccine process development and ensure process consistency. (C) 2016 Published by Elsevier B.V. C1 [Lancaster, Catherine; Pristatsky, Pavlo; Hoang, Van M.; Casimiro, Danilo R.; Rustandi, Richard; Ha, Sha] Merck Res Labs, Vaccine Bioproc Res & Dev, West Point, PA 19486 USA. [Schwartz, Richard M.] NIAID, Vaccine Prod Program, Vaccine Res Ctr, NIH, Gaithersburg, MD 20878 USA. RP Ha, S (reprint author), Merck Res Labs, Vaccine Bioproc Res & Dev, West Point, PA 19486 USA. EM sha_ha@merck.com NR 30 TC 0 Z9 0 U1 4 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 EI 1873-376X J9 J CHROMATOGR B JI J. Chromatogr. B PD OCT 1 PY 2016 VL 1032 SI SI BP 218 EP 223 DI 10.1016/j.jchromb.2016.04.025 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA DY1LV UT WOS:000384857400024 PM 27157808 ER PT J AU Gordon, SN Liyanage, NPM Doster, MN Vaccari, M Vargas-Inchaustegui, DA Pegu, P Schifanella, L Shen, XY Tomaras, GD Rao, M Billings, EA Schwartz, J Prado, I Bobb, K Zhang, WL Montefiori, DC Foulds, KE Ferrari, G Robert-Guroff, M Roederer, M Phan, TB Forthal, DN Stablein, DM Phogat, S Venzon, DJ Fouts, T Franchini, G AF Gordon, Shari N. Liyanage, Namal P. M. Doster, Melvin N. Vaccari, Monica Vargas-Inchaustegui, Diego A. Pegu, Poonam Schifanella, Luca Shen, Xiaoying Tomaras, Georgia D. Rao, Mangala Billings, Erik A. Schwartz, Jennifer Prado, Ilia Bobb, Kathryn Zhang, Wenlei Montefiori, David C. Foulds, Kathryn E. Ferrari, Guido Robert-Guroff, Marjorie Roederer, Mario Phan, Tran B. Forthal, Donald N. Stablein, Donald M. Phogat, Sanjay Venzon, David J. Fouts, Timothy Franchini, Genoveffa TI Boosting of ALVAC-SIV Vaccine-Primed Macaques with the CD4-SIVgp120 Fusion Protein Elicits Antibodies to V2 Associated with a Decreased Risk of SIVmac251 Acquisition SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DEPENDENT CELLULAR CYTOTOXICITY; IMMUNODEFICIENCY VIRUS SIV; SIMIAN IMMUNODEFICIENCY; RHESUS MACAQUES; HIV-1 VACCINE; MEDIATED CYTOTOXICITY; SHIV CHALLENGE; GAG/POL/NEF VACCINE; ENVELOPE PROTEIN; EFFICACY TRIAL AB The recombinant ALVAC vaccine coupled with the monomeric gp120/alum protein have decreased the risk of HIV and SIV acquisition. Ab responses to the V1/V2 regions have correlated with a decreased risk of virus acquisition in both humans and macaques. We hypothesized that the breadth and functional profile of Abs induced by an ALVAC/envelope protein regimen could be improved by substituting the monomeric gp120 boost, with the full-length single-chain (FLSC) protein. FLSC is a CD4-gp120 fusion immunogen that exposes cryptic gp120 epitopes to the immune system. We compared the immunogenicity and relative efficiency of an ALVAC-SIV vaccine boosted either with bivalent FLSC proteins or with monomeric gp120 in alum. FLSC was superior to monomeric gp120 in directing Abs to the C3 alpha 2 helix, the V5 loop, and the V3 region that contains the putative CCR5 binding site. In addition, FLSC boosting elicited significantly higher binding Abs to V2 and increased both the Ab-dependent cellular cytotoxicity activity and the breadth of neutralizing Abs. However, the FLSC vaccine regimen demonstrated only a trend in vaccine efficacy, whereas the monomeric gp120 regimen significantly decreased the risk of SIVmac251 acquisition. In both vaccine regimens, anti-V2 Abs correlated with a decreased risk of virus acquisition but differed with regard to systemic or mucosal origin. In the FLSC regimen, serum Abs to V2 correlated, whereas in the monomeric gp120 regimen, V2 Abs in rectal secretions, the site of viral challenge, were associated with efficacy. C1 [Gordon, Shari N.; Liyanage, Namal P. M.; Doster, Melvin N.; Vaccari, Monica; Pegu, Poonam; Schifanella, Luca; Franchini, Genoveffa] NCI, Anim Models & Vaccine Sect, NIH, 41 Lib Dr,Bldg 41,Room D804, Bethesda, MD 20892 USA. [Vargas-Inchaustegui, Diego A.; Robert-Guroff, Marjorie] NCI, Immune Biol Retroviral Infect Sect, Vaccine Branch, Bethesda, MD 20892 USA. [Shen, Xiaoying; Tomaras, Georgia D.; Montefiori, David C.; Ferrari, Guido] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Rao, Mangala; Billings, Erik A.] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD 20910 USA. [Schwartz, Jennifer; Prado, Ilia; Bobb, Kathryn; Zhang, Wenlei; Fouts, Timothy] Profectus BioSci Inc, Baltimore, MD 21224 USA. [Foulds, Kathryn E.; Roederer, Mario] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Phan, Tran B.; Forthal, Donald N.] Univ Calif Irvine, Div Infect Dis, Dept Med, Sch Med, Irvine, CA 92868 USA. [Stablein, Donald M.] Emmes Corp, Rockville, MD 20850 USA. [Phogat, Sanjay] Sanofi Pasteur, Swiftwater, PA 18370 USA. [Venzon, David J.] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. RP Franchini, G (reprint author), NCI, Anim Models & Vaccine Sect, NIH, 41 Lib Dr,Bldg 41,Room D804, Bethesda, MD 20892 USA. EM franchig@mail.nih.gov FU Intramural NIH HHS [Z01 BC005688-17] NR 53 TC 0 Z9 0 U1 2 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2016 VL 197 IS 7 BP 2726 EP 2737 DI 10.4049/jimmunol.1600674 PG 12 WC Immunology SC Immunology GA DY3OX UT WOS:000385004600022 PM 27591322 ER PT J AU Roberts, LM Crane, DD Wehrly, TD Fletcher, JR Jones, BD Bosio, CM AF Roberts, Lydia M. Crane, Deborah D. Wehrly, Tara D. Fletcher, Joshua R. Jones, Bradley D. Bosio, Catharine M. TI Inclusion of Epitopes That Expand High-Avidity CD4(+) T Cells Transforms Subprotective Vaccines to Efficacious Immunogens against Virulent Francisella tularensis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RESPIRATORY VIRUS-INFECTIONS; TULAREMIA VACCINES; PROTECTIVE IMMUNITY; INTERFERON-GAMMA; C57BL/6 MICE; IFN-GAMMA; LVS; PULMONARY; LIVE; IDENTIFICATION AB T cells are the immunological cornerstone in host defense against infections by intracellular bacterial pathogens, such as virulent Francisella tularensis spp. tularensis (Ftt). The general paucity of novel vaccines for Ftt during the past 60 y can, in part, be attributed to the poor understanding of immune parameters required to survive infection. Thus, we developed a strategy utilizing classical immunological tools to elucidate requirements for effective adaptive immune responses directed against Ftt. Following generation of various Francisella strains expressing well-characterized lymphocytic choriomeningitis virus epitopes, we found that survival correlated with persistence of Ag-specific CD4(+) T cells. Function of these cells was confirmed in their ability to more effectively control Ftt replication in vitro. The importance of understanding the Ag-specific response was underscored by our observation that inclusion of an epitope that elicits high-avidity CD4(+) T cells converted a poorly protective vaccine to one that engenders 100% protection. Taken together, these data suggest that improved efficacy of current tularemia vaccine platforms will require targeting appropriate Ag-specific CD4(+) T cell responses and that elucidation of Francisella epitopes that elicit high-avidity CD4(+) T cell responses, specifically in humans, will be required for successful vaccine development. C1 [Roberts, Lydia M.; Crane, Deborah D.; Wehrly, Tara D.; Bosio, Catharine M.] NIAID, Immun Pulm Pathogens Sect, Bacteriol Lab, Rocky Mt Labs,NIH, 903 S 4th St, Hamilton, MT 59840 USA. [Fletcher, Joshua R.; Jones, Bradley D.] Univ Iowa, Carver Coll Med, Dept Microbiol, Iowa City, IA 52242 USA. RP Bosio, CM (reprint author), NIAID, Immun Pulm Pathogens Sect, Bacteriol Lab, Rocky Mt Labs,NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM bosioc@niaid.nih.gov FU Intramural NIH HHS [Z01 AI001013-02]; NIAID NIH HHS [HHSN272201300006C] NR 38 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2016 VL 197 IS 7 BP 2738 EP 2747 DI 10.4049/jimmunol.1600879 PG 10 WC Immunology SC Immunology GA DY3OX UT WOS:000385004600023 PM 27543611 ER PT J AU Gazzinelli-Guimaraes, PH Bonne-Annee, S Fujiwara, RT Santiago, HC Nutman, TB AF Gazzinelli-Guimaraes, Pedro H. Bonne-Annee, Sandra Fujiwara, Ricardo T. Santiago, Helton C. Nutman, Thomas B. TI Allergic Sensitization Underlies Hyperreactive Antigen-Specific CD4(+) T Cell Responses in Coincident Filarial Infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TROPICAL PULMONARY EOSINOPHILIA; SPIRALIS NEWBORN LARVAE; ASCARIS-LUMBRICOIDES; IGE RESPONSES; LYMPHATIC FILARIASIS; HELMINTH INFECTIONS; SCHISTOSOMA-MANSONI; NECATOR-AMERICANUS; IMMUNOGLOBULIN-E; SCHOOL-CHILDREN AB Among the various hypotheses put forward to explain the modulatory influence of helminth infection on allergic effector responses in humans, the IL-10-induced suppression of Th2-associated responses has been the leading candidate. To explore this helminth/allergy interaction more fully, parasite-and allergen-specific CD4(+) T cell responses in 12 subjects with filarial infections, and coincident allergic sensitization (filarial [Fil](+)allergy [A](+)) were compared with the responses to three appropriate control groups (Fil(-)A(-) [n = 13], Fil(-)A(+) [n = 12], Fil(+)A(-) [n = 11]). The most important findings revealed that Fil(+)A(+) had marked (p < 0.0001 for all cytokines) increases in parasite Ag-driven Th2 (IL-4, IL-5, IL-13), Th9 (IL-9), and the regulatory (IL-10) cytokines when compared with Fil(+)A(-). Moreover, using multiparameter flow cytometry, filarial parasite Ag induced a marked increase in not only the frequency of CD4(+) T cells producing IL-4, IL-5, IL-2, and TNF-alpha in Fil(+)A(+) when compared with Fil(+)A(-) patients, but also in the frequencies of polyfunctional Th2-like (CD4(+)IL-4(+)IL-5(+) and CD4(+)IL-2(+)IL-4(+)IL-5(+)TNF-alpha(+)) cells. The Th2-associated responses seen in the Fil(+)A(+) group were correlated with serum IgE levels (p < 0.01, r = 0.5165 for IL-4; p < 0.001, r = 0.5544 for IL-5; and p < 0.001, r = 0.4901 for IL-13) and levels of circulating eosinophils (p < 0.0116, r = 0.5656) and their degranulation/activation products (major basic protein [p < 0.001, r = 0.7353] and eosinophil-derived neurotoxin [p < 0.01, r = 0.7059]). CD4(+) responses to allergen were not different (to a large extent) among the groups. Taken together, our data suggest that allergic sensitization coincident with filarial infection drives parasite Ag-specific T cell hyperresponsiveness, which is characterized largely by an augmented Th2-dominated immune response. C1 [Gazzinelli-Guimaraes, Pedro H.; Bonne-Annee, Sandra; Nutman, Thomas B.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Gazzinelli-Guimaraes, Pedro H.; Fujiwara, Ricardo T.] Univ Fed Minas Gerais, Inst Biol Sci, Dept Parasitol, BR-31270901 Belo Horizonte, MG, Brazil. [Santiago, Helton C.] Univ Fed Minas Gerais, Inst Biol Sci, Dept Immunol & Biochem, BR-31270901 Belo Horizonte, MG, Brazil. RP Nutman, TB (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr,Bldg 4,Room B1-03, Bethesda, MD 20892 USA. EM tnutman@niaid.nih.gov RI Gazzinelli-Guimaraes, Pedro Henrique/E-7693-2013; Fujiwara, Ricardo/J-7579-2012 OI Gazzinelli-Guimaraes, Pedro Henrique/0000-0003-4932-2206; Fujiwara, Ricardo/0000-0002-4713-575X FU Intramural NIH HHS [Z01 AI000197-28] NR 76 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2016 VL 197 IS 7 BP 2772 EP 2779 DI 10.4049/jimmunol.1600829 PG 8 WC Immunology SC Immunology GA DY3OX UT WOS:000385004600026 PM 27566825 ER PT J AU Chan, YN Boesch, AW Osei-Owusu, NY Emileh, A Crowley, AR Cocklin, SL Finstad, SL Linde, CH Howell, RA Zentner, I Cocklin, S Miles, AR Eckman, JW Alter, G Schmitz, JE Ackerman, ME AF Chan, Ying N. Boesch, Austin W. Osei-Owusu, Nana Y. Emileh, Ali Crowley, Andrew R. Cocklin, Sarah L. Finstad, Samantha L. Linde, Caitlyn H. Howell, Rebecca A. Zentner, Isaac Cocklin, Simon Miles, Adam R. Eckman, Joshua W. Alter, Galit Schmitz, Joern E. Ackerman, Margaret E. TI IgG Binding Characteristics of Rhesus Macaque Fc gamma R SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HIGH-THROUGHPUT; PROTECTIVE EFFICACY; ANTIBODY; AFFINITY; RECEPTOR; HIV; COMPLEMENT; CHALLENGES; SUBCLASSES; VACCINES AB Indian rhesus macaques (Macaca mulatta) are routinely used in preclinical studies to evaluate therapeutic Abs and candidate vaccines. The efficacy of these interventions in many cases is known to rely heavily on the ability of Abs to interact with a set of Ab Fc gamma R expressed on innate immune cells. Yet, despite their presumed functional importance, M. mulatta Ab receptors are largely uncharacterized, posing a fundamental limit to ensuring accurate interpretation and translation of results from studies in this model. In this article, we describe the binding characteristics of the most prevalent allotypic variants of M. mulatta FcgR for binding to both human and M. mulatta IgG of varying subclasses. The resulting determination of the affinity, specificity, and glycan sensitivity of these receptors promises to be useful in designing and evaluating studies of candidate vaccines and therapeutic Abs in this key animal model and exposes significant evolutionary divergence between humans and macaques. C1 [Chan, Ying N.; Boesch, Austin W.; Emileh, Ali; Ackerman, Margaret E.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Osei-Owusu, Nana Y.; Crowley, Andrew R.; Ackerman, Margaret E.] Dartmouth Coll, Mol & Cellular Biol Program, Hanover, NH 03755 USA. [Cocklin, Sarah L.; Finstad, Samantha L.; Linde, Caitlyn H.; Howell, Rebecca A.; Schmitz, Joern E.] Harvard Med Sch, Ctr Virol & Vaccine Res, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Zentner, Isaac; Cocklin, Simon] Drexel Univ, Coll Med, Dept Biochem & Mol Biol, Philadelphia, PA 19102 USA. [Miles, Adam R.; Eckman, Joshua W.] Wasatch Microfluid, Salt Lake City, UT 84103 USA. [Linde, Caitlyn H.; Alter, Galit] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA. [Finstad, Samantha L.] NIH, Off AIDS Res, Bldg 10, Bethesda, MD 20892 USA. [Schmitz, Joern E.] Fraunhofer Inst Mol Biol & Appl Ecol, Dept Immunotherapy, Aachen, Germany. RP Ackerman, ME (reprint author), Dartmouth Coll, 14 Engn Dr, Hanover, NH 03755 USA. EM margaret.e.ackerman@dartmouth.edu FU NIAID NIH HHS [HHSN272201100023C, P01 AI120756, R01 AI102691, R56 AI097315, UM1 AI100645] NR 30 TC 1 Z9 1 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2016 VL 197 IS 7 BP 2936 EP 2947 DI 10.4049/jimmunol.1502252 PG 12 WC Immunology SC Immunology GA DY3OX UT WOS:000385004600042 PM 27559046 ER PT J AU Absinta, M Reich, DS Filippi, M AF Absinta, Martina Reich, Daniel S. Filippi, Massimo TI Spring cleaning: time to rethink imaging research lines in MS? SO JOURNAL OF NEUROLOGY LA English DT Review DE Multiple sclerosis; Neuroimaging; Biomarkers ID MULTIPLE-SCLEROSIS LESIONS; OPTICAL COHERENCE TOMOGRAPHY; REGIONAL HIPPOCAMPAL ATROPHY; WHITE-MATTER LESIONS; BLOOD-BRAIN-BARRIER; CORTICAL-LESIONS; IN-VIVO; 7 TESLA; COGNITIVE IMPAIRMENT; SPINAL-CORD AB Together with recently advanced MRI technological capability, new needs and updated questions are emerging in imaging research in multiple sclerosis (MS), especially with respect to the identification of novel in vivo biomarkers of MS-relevant pathological processes. Expected benefits will involve approaches to diagnosis and clinical classification. In detail, three main points of discussion are addressed in this review: (1) new imaging biomarkers (centrifugal/centripetal lesion enhancement, central vein, paramagnetic rims at the lesion edge, subpial cortical demyelination); (2) thinking about high-resolution MR from a pathological perspective (from postmortem to in vivo staging); and (3) the clinical utility of quantitative MRI. In this context, research efforts should increasingly be focused on the direct in vivo visualization of "hidden" inflammation, beyond what can be detected with conventional gadolinium-based methods, as well as remyelination and repair, since these are likely to represent critical pathological processes and potential therapeutic targets. Concluding remarks concern the limitations, challenges, and ultimately clinical role of non-conventional MRI techniques. C1 [Absinta, Martina; Filippi, Massimo] Univ Vita Salute San Raffaele, Inst Expt Neurol, San Raffaele Sci Inst, Hosp San Raffaele,Neuroimaging Res Unit,Div Neuro, Via Olgettina 60, I-20132 Milan, Italy. [Absinta, Martina; Reich, Daniel S.] NINDS, Translat Neuroradiol Unit, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. RP Filippi, M (reprint author), Univ Vita Salute San Raffaele, Inst Expt Neurol, San Raffaele Sci Inst, Hosp San Raffaele,Neuroimaging Res Unit,Div Neuro, Via Olgettina 60, I-20132 Milan, Italy. EM filippi.massimo@hsr.it OI Filippi, Massimo/0000-0002-5485-0479 FU Intramural Research Program of NINDS, NIH FX Special thanks to Prof. Andrea Falini (Head of the Department of Neuroradiology, San Raffaele Hospital), Dr. Vittorio Martinelli (Head of Clinical Trials Unit, Division of Neuroscience, San Raffaele Hospital), and Dr. Pascal Sati and Dr. Govind Nair (staff scientists, NINDS, NIH) for valuable advice, assistance with MRI data acquisition/post-processing, and help in figures' preparation. This work was supported in part by the Intramural Research Program of NINDS, NIH. NR 116 TC 0 Z9 0 U1 3 U2 3 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 EI 1432-1459 J9 J NEUROL JI J. Neurol. PD OCT PY 2016 VL 263 IS 10 BP 1893 EP 1902 DI 10.1007/s00415-016-8060-0 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA DY5WA UT WOS:000385173900001 PM 26886204 ER PT J AU Buch, S Chivero, ET Hoare, J Jumare, J Nakasujja, N Mudenda, V Paul, R Kanmogne, GD Sacktor, N Wood, C Royal, W Joseph, J AF Buch, Shilpa Chivero, Ernest T. Hoare, Jackie Jumare, Jibreel Nakasujja, Noeline Mudenda, Victor Paul, Robert Kanmogne, Georgette D. Sacktor, Ned Wood, Charles Royal, Walter Joseph, Jeymohan TI Proceedings from the NIMH symposium on "NeuroAIDS in Africa: neurological and neuropsychiatric complications of HIV" SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE Human immunodeficiency virus (HIV); HIV-associated neurocognitive disorders (HAND); NeuroAIDS ID COGNITIVE IMPAIRMENT; TAT; DISORDERS; THERAPY; DISEASE; HAART AB Despite major advances in HIV-1 treatment, the prevalence of HIV-associated neurocognitive disorders (HAND) remains a problem, particularly as individuals on suppressive treatment continue to live longer. To facilitate discussion on emerging and future directions in HAND research, a meeting was held in Durban, South Africa in March 2015 as part of the Society of Neuroscientists of Africa (SONA) conference. The objective of the meeting was to assess the impact of HIV subtype diversity on HAND and immunological dysfunction. The meeting brought together international leaders in the area of neurological complications of HIV-1 infection with special focus on the African population. Research presentations indicated that HAND was highly prevalent and that inflammatory cytokines and immune-activation played important roles in progression of neurocognitive impairment. Furthermore, children on antiretroviral therapy were also at risk for developing neurocognitive impairment. With respect to the effect of HIV-1 subtype diversity, analyses of HIV-1 clade C infection among South Africans revealed that clade C infection induced cognitive impairment that was independent of the substitution in HIV-1 Trans-Activator of Transcription (Tat; C31S). At the cellular level, a Zambian study showed that clade C infection resulted in reduced brain cell death compared with clade B infection suggesting clade specific variations in mediating brain cell injury. Furthermore, ex vivo Tat protein from clade CRF02_AG, prevalent in West/ Central Africa, exhibited reduced disruption of brain endothelium compared with clade B Tat protein. Discussions shed light on future research directions aimed at understanding biomarkers and disease mechanisms critical for HAND. C1 [Buch, Shilpa; Chivero, Ernest T.; Kanmogne, Georgette D.] Univ Nebraska Med Ctr, Omaha, NE 68198 USA. [Hoare, Jackie] Univ Cape Town, Cape Town, South Africa. [Jumare, Jibreel; Royal, Walter] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Nakasujja, Noeline] Makerere Univ, Kampala, Uganda. [Mudenda, Victor] Univ Zambia, Lusaka, Zambia. [Paul, Robert] Univ Missouri, St Louis, MO 63121 USA. [Sacktor, Ned] Johns Hopkins Univ, Baltimore, MD USA. [Wood, Charles] Univ Nebraska, Lincoln, NE USA. [Joseph, Jeymohan] NIMH, Div AIDS Res, NIH, Bethesda, MD 20892 USA. RP Buch, S (reprint author), Univ Nebraska Med Ctr, Omaha, NE 68198 USA.; Joseph, J (reprint author), NIMH, Div AIDS Res, NIH, Bethesda, MD 20892 USA. EM sbuch@unmc.edu; jjeymoha@mail.nih.gov FU National Institutes of Health [MH094160, DA036157] FX The authors acknowledge funding from National Institutes of Health: MH094160 (to GDK); DA036157 (to SB). NR 16 TC 0 Z9 0 U1 3 U2 3 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 OCT PY 2016 VL 22 IS 5 BP 699 EP 702 DI 10.1007/s13365-016-0467-y PG 4 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA DY4JM UT WOS:000385064800020 PM 27473196 ER PT J AU Lindenberg, L Ahlman, M Turkbey, B Mena, E Choyke, P AF Lindenberg, Liza Ahlman, Mark Turkbey, Baris Mena, Esther Choyke, Peter TI Evaluation of Prostate Cancer with PET/MRI SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE multiparametric MRI; PET/MRI; prostate cancer ID SEMINAL-VESICLE INVASION; PLANAR BONE-SCINTIGRAPHY; INTEGRATED WHOLE-BODY; FUSION-GUIDED BIOPSY; EXTRACAPSULAR EXTENSION; INITIAL-EXPERIENCE; F-18-DCFBC PET/CT; CHOLINE-PET/CT; METASTASES; MRI AB In the ongoing effort to understand and cure prostate cancer, imaging modalities are constantly evolving to assist in clinical decisions. Multiparametric MRI can be used to direct prostate biopsies, improve diagnostic yield, and help clinicians make more accurate decisions. PET is superior in providing biologic information about the cancer and is sensitive and highly specific. Integrated PET/MRI is a welcome technical advance with great potential to influence the diagnosis and management of prostate cancer in clinical practice. C1 [Lindenberg, Liza; Turkbey, Baris; Choyke, Peter] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room B3B402 MS 1088,10 Ctr Dr, Bethesda, MD 20892 USA. [Ahlman, Mark] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Mena, Esther] Johns Hopkins Med Inst, Russell H Morgan Dept Radiol & Radiol Sci, 600 N Wolfe St, Baltimore, MD 21205 USA. RP Lindenberg, L (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room B3B402 MS 1088,10 Ctr Dr, Bethesda, MD 20892 USA. EM liza.lindenberg@mail.nih.gov NR 51 TC 2 Z9 2 U1 3 U2 3 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD OCT PY 2016 VL 57 SU 3 BP 111S EP 116S DI 10.2967/jnumed.115.169763 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DY3AB UT WOS:000384962100019 PM 27694163 ER PT J AU Kiess, AP Minn, I Vaidyanathan, G Hobbs, RF Josefsson, A Shen, C Brummet, M Chen, Y Choi, J Koumarianou, E Baidoo, K Brechbiel, MW Mease, RC Sgouros, G Zalutsky, MR Pomper, MG AF Kiess, Ana P. Minn, Il Vaidyanathan, Ganesan Hobbs, Robert F. Josefsson, Anders Shen, Colette Brummet, Mary Chen, Ying Choi, Jaeyeon Koumarianou, Eftychia Baidoo, Kwamena Brechbiel, Martin W. Mease, Ronnie C. Sgouros, George Zalutsky, Michael R. Pomper, Martin G. TI (2S)-2-(3-(1-Carboxy-5-(4-At-211-Astatobenzamido)Pentyl) Ureido)-Pentanedioic Acid for PSMA-Targeted alpha-Particle Radiopharmaceutical Therapy SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE oncology: GU; radionuclide therapy; radiopharmaceuticals; alpha emitter; astatine; prostate cancer; prostate-specific membrane antigen; radiation dosimetry ID METASTATIC PROSTATE-CANCER; MALIGNANT HUMAN TISSUES; MEMBRANE ANTIGEN PSMA; SURVIVAL; RADIOIMMUNOTHERAPY; EXPRESSION; INHIBITORS; F-18-DCFBC; DOSIMETRY; SERIES AB Alpha-particle emitters have a high linear energy transfer and short range, offering the potential for treating micrometastases while sparing normal tissues. We developed a urea-based, At-211-labeled small molecule targeting prostate-specific membrane antigen (PSMA) for the treatment of micrometastases due to prostate cancer (PC). Methods: PSMA-targeted (2S)-2-(3-(1-carboxy-5-(4-At-211-astatobenzami do) pentyl)ureido)-pentanedioic acid (At-211-6) was synthesized. Cellular uptake and clonogenic survival were tested in PSMA-positive (PSMA+) PC3 PIP and PSMA-negative (PSMA-) PC3 flu human PC cells after At-211-6 treatment. The antitumor efficacy of At-211-6 was evaluated in mice bearing PSMA+ PC3 PIP and PSMA- PC3 flu flank xenografts at a 740-kBq dose and in mice bearing PSMA+, luciferase-expressing PC3-ML micrometastases. Biodistribution was determined in mice bearing PSMA+ PC3 PIP and PSMA(-) PC3 flu flank xenografts. Suborgan distribution was evaluated using alpha-camera images, and microscale dosimetry was modeled. Longterm toxicity was assessed in mice for 12 mo. Results: At-211-6 treatment resulted in PSMA-specific cellular uptake and decreased clonogenic survival in PSMA+ PC3 PIP cells and caused significant tumor growth delay in PSMA+ PC3 PIP flank tumors. Significantly improved survival was achieved in the newly developed PSMA+ micrometastatic PC model. Biodistribution showed uptake of At-211-6 in PSMA+ PC3 PIP tumors and in kidneys. Microscale kidney dosimetry based on alpha-camera images and a nephron model revealed hot spots in the proximal renal tubules. Long-term toxicity studies confirmed that the dose-limiting toxicity was late radiation nephropathy. Conclusion: PSMA-targeted At-211-6 alpha-particle radiotherapy yielded significantly improved survival in mice bearing PC micrometastases after systemic administration. At-211-6 also showed uptake in renal proximal tubules resulting in late nephrotoxicity, highlighting the importance of long-term toxicity studies and microscale dosimetry. C1 [Kiess, Ana P.; Hobbs, Robert F.; Shen, Colette; Sgouros, George; Pomper, Martin G.] Johns Hopkins Univ, Sch Med, Dept Radiat Oncol & Mol Radiat Sci, Baltimore, MD USA. [Minn, Il; Josefsson, Anders; Brummet, Mary; Chen, Ying; Mease, Ronnie C.; Sgouros, George; Pomper, Martin G.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. [Vaidyanathan, Ganesan; Choi, Jaeyeon; Koumarianou, Eftychia; Zalutsky, Michael R.] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. [Baidoo, Kwamena; Brechbiel, Martin W.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Pomper, MG (reprint author), Johns Hopkins Med Sch, 1550 Orleans St,492 CRB 2, Baltimore, MD 21287 USA. EM mpomper@jhmi.edu FU NIH [CA116477, CA184228, CA134675, CA183031, CA157542, EB005324]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX The costs of publication of this article were defrayed in part by the payment of page charges. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 USC section 1734. This work was supported by NIH CA116477, CA184228, CA134675, CA183031, CA157542, and EB005324 and in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. No other potential conflict of interest relevant to this article was reported. NR 32 TC 2 Z9 2 U1 15 U2 15 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD OCT PY 2016 VL 57 IS 10 BP 1569 EP 1575 DI 10.2967/jnumed.116.174300 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DY2ZZ UT WOS:000384961900022 PM 27230930 ER PT J AU Von Korff, M Scher, AI Helmick, C Carter-Pokras, O Dodick, DW Goulet, J Hamill-Ruth, R LeResche, L Porter, L Tait, R Terman, G Veasley, C Mackey, S AF Von Korff, Michael Scher, Ann I. Helmick, Charles Carter-Pokras, Olivia Dodick, David W. Goulet, Joseph Hamill-Ruth, Robin LeResche, Linda Porter, Linda Tait, Raymond Terman, Gregory Veasley, Christin Mackey, Sean TI United States National Pain Strategy for Population Research: Concepts, Definitions, and Pilot Data SO JOURNAL OF PAIN LA English DT Article DE Chronic pain; epidemiology; health services research; prevalence; electronic databases ID CROSS-SECTIONAL SURVEY; CHRONIC BACK-PAIN; SEVERITY; MODERATE; PATIENT; MILD; COMORBIDITY; PREVALENCE; DISABILITY; ARTHRITIS AB National Pain Strategy population research objectives include: estimating chronic pain prevalence, studying pain treatment with electronic health care data, and developing metrics to assess progress in reducing chronic pain impact. In this article, the National Pain Strategy Population Research Workgroup reviews concepts relevant to achieving these aims. High-impact chronic pain was defined as persistent pain with substantial restriction of life activities lasting 6 months or more. In pilot work, we tested a brief assessment of high-impact chronic pain, and used electronic health records data to describe pain-related health care. A mail survey of adult health plan enrollees (N = 770) reported that 14% had high-impact chronic pain. Relative to persons with lower-impact chronic pain, those with high-impact chronic pain were more often frequent users of health care for pain, reported lower quality of life, greater pain-related interference with activities, and more often reported pain at multiple anatomic locations. Analyses of health care data (N = 289,464) reported that pain patients had higher health care costs compared with others and that pain services were typically delivered in primary care. These results support the feasibility of developing data on chronic pain through national health interview surveys and large electronic health care databases. Perspective: Pilot analyses supported the feasibility of brief chronic pain assessments suitable for national health surveys and use of electronic health care databases to develop data regarding trends in the delivery of pain treatments, costs, and effectiveness. These methods are relevant to achieving the aims of the US National Pain Strategy. (C) 2016 by the American Pain Society C1 [Von Korff, Michael] Grp Hlth Res Inst, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. [Scher, Ann I.] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biostat, Bethesda, MD 20814 USA. [Helmick, Charles] Ctr Dis Control & Prevent, Atlanta, GA USA. [Carter-Pokras, Olivia] Univ Maryland, Sch Publ Hlth, College Pk, MD 20742 USA. [Dodick, David W.] Mayo Clin, Coll Med, Phoenix, AZ USA. [Goulet, Joseph] Yale Univ, Sch Med, New Haven, CT USA. [Hamill-Ruth, Robin] Univ Virginia Hlth Syst, Charlottesville, VA USA. [LeResche, Linda] Univ Washington, Sch Dent, Seattle, WA 98195 USA. [Porter, Linda] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Tait, Raymond] St Louis Univ, Sch Med, Dept Psychiat, St Louis, MO 63103 USA. [Terman, Gregory] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Veasley, Christin] Chron Pain Res Alliance, Milwaukee, WI USA. [Mackey, Sean] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. RP Von Korff, M (reprint author), Grp Hlth Res Inst, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. EM vonkorff.m@ghc.org OI Goulet, Joseph/0000-0002-0842-804X FU NINDS; IH Inter-Agency Pain Research Coordinating Committee [AG034181]; Pfizer Inc.; Healthlogix; Haymarket Media Group, Ltd.; SAGE Publishing; Synergy; Allergan; Lippincott Williams Wilkins; Oxford University Press; Cambridge University Press FX The pilot data collection reported in this paper was supported by a supplemental award from NINDS and the NIH Inter-Agency Pain Research Coordinating Committee to a National Institute on Aging grant (AG034181, Von Korff, Principal Investigator).; Dr. Von Korff is the Principal Investigator of grants to GHRI from Pfizer Inc. that concern opioids. Dr. Scher is an advisory board member and consultant for Allergan. Dr. Tait's spouse serves on the speaker's bureau for Lilly Pharmaceuticals. David W. Dodick, MD, in the past 12 months, has served on advisory boards and has consulted for Allergan, Amgen, Alder, CoLucid, Merck, ENeura, Eli Lilly & Company, Autonomic Technologies, Teva, Tonix, Novartis, Supernus, ScionNeurostim, Boston Scientific. Within the past 12 months, Dr. Dodick has received royalties, funding for travel, speaking, or editorial activities from the following: Healthlogix, Haymarket Media Group, Ltd., SAGE Publishing, Synergy, Allergan, Lippincott Williams & Wilkins, Oxford University Press, and Cambridge University Press; he serves as Editor-in-Chief of Cephalalgia and on the editorial boards of The Neurologist, Lancet Neurology, and Postgraduate Medicine. The remaining authors report no conflicts. NR 41 TC 1 Z9 1 U1 4 U2 4 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD OCT PY 2016 VL 17 IS 10 BP 1068 EP 1080 DI 10.1016/j.jpain.2016.06.009 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DY1SF UT WOS:000384874000003 PM 27377620 ER PT J AU Ruiz-Rodado, V Nicoli, ER Probert, F Smith, DA Morris, L Wassif, CA Platt, FM Grootveld, M AF Ruiz-Rodado, Victor Nicoli, Elena-Raluca Probert, Fay Smith, David A. Morris, Lauren Wassif, Christopher A. Platt, Frances M. Grootveld, Martin TI H-1 NMR-Linked Metabolomics Analysis of Liver from a Mouse Model of NP-C1 Disease SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE NP-Cl disease; liver damage/dysfunction; fibrosis-cirrhosis; NMR-based metabolomics; biomarkers; amino acid biosynthesis and metabolism; nicotinate and niacinamide metabolism; 3-hydroxyphenylacetate; metabolic pathway analysis ID NIEMANN-PICK-DISEASE; CHAIN AMINO-ACIDS; C DISEASE; GLUTATHIONE METABOLISM; METABONOMIC APPROACH; URINARY-EXCRETION; STORAGE DISORDER; PHENOLIC-ACIDS; RANDOM FORESTS; MURINE MODEL AB Clinical manifestations of Niemann-Pick type Cl (NP-C1) disease include neonatal hepatosplenomegaly and in some patients progressive liver dysfunction and failure. This study involved a H-1 NMR-linked metabolomics analysis of liver samples collected from a NP-C1 disease mutant mouse model in order to explore time-dependent imbalances in metabolic pathways associated with NP-C1 liver dysfunction, including fibrosis. NP-Cl mutant (Npc1(-/-); NP-C1), control (Npcl(+/+); WT), and NP-C1 heterozygous mice (Npc1(+/-); HET) were generated from heterozygote matings. Aqueous extracts of these liver samples collected at time points of 3, 6, 9, and 11 weeks were subjected to high-resolution NMR analysis, and multivariate (MV) metabolomics analyses of data sets acquired were performed. A MV random forests (RFs) model effectively discriminated between NP-C1 and a combined WT/HET hepatic NMR profiles with very high predictive accuracy and reliability. Key distinguishing features included significant upregulations in the hepatic concentrations of phenylalanine, tyrosine, glutamate, lysine/ornithine, valine, threonine, and hypotaurine/methionine, and diminished levels of nicotinate/niacinamide, inosine, phosphoenolpyruvate, and 3-hydroxyphenylacetate. Quantitative pathway topological analysis confirmed that imbalances in tyrosine biosynthesis, and hepatic phenylalanine, tyrosine, glutamate/glutamine, and nicotinate/niacinamide metabolism were involved in the pathogenesis of NP-C1 disease-associated liver dysfunction/damage. H-1 NMR-linked metabolomics analysis provides valuable biomarker information regarding hepatic dysfunction or damage in NP-C1 disease. C1 [Ruiz-Rodado, Victor; Probert, Fay; Grootveld, Martin] De Montfort Univ, Leicester Sch Pharm, Leicester LE1 9BH, Leics, England. [Nicoli, Elena-Raluca; Smith, David A.; Morris, Lauren; Wassif, Christopher A.; Platt, Frances M.] Univ Oxford, Dept Pharmacol, Mansfield Rd, Oxford OX1 3QT, England. [Wassif, Christopher A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. RP Grootveld, M (reprint author), De Montfort Univ, Leicester Sch Pharm, Leicester LE1 9BH, Leics, England. EM mgrootveld@dmu.ac.uk FU SPARKS Medical Charity for Children's Health; Action Medical research; Niemann-Pick Research Foundation FX We are very grateful to the SPARKS Medical Charity for Children's Health for providing funding for a Research Fellowship to F.P. and the Hope Against Cancer Charity and De Montfort University, Leicester, for the provision of doctoral training bursaries to V.R-R. E.-R.N. is supported by Action Medical research, and D.S. is supported by the Niemann-Pick Research Foundation. F.M.P. is a Royal Society Wolfson Research Merit Award holder. NR 90 TC 0 Z9 0 U1 3 U2 3 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 OCT PY 2016 VL 15 IS 10 BP 3511 EP 3527 DI 10.1021/acs.jproteome.6b00238 PG 17 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA DY4FJ UT WOS:000385054100007 PM 27503774 ER PT J AU Park, S Thompson, FE McGuire, LC Pan, LP Galuska, DA Blanck, HM AF Park, Sohyun Thompson, Frances E. McGuire, Lisa C. Pan, Liping Galuska, Deborah A. Blanck, Heidi M. TI Sociodemographic and Behavioral Factors Associated with Added Sugars Intake among US Adults SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS LA English DT Article DE Added sugars; Sugar-sweetened beverages; Sweet food; Sociodemographic characteristics; Behaviors ID SWEETENED BEVERAGE INTAKE; FAMILY-HISTORY; CIGARETTE-SMOKING; TASTE INTENSITY; YOUNG-ADULTS; HEALTH; ALCOHOLISM; STATES; CONSUMPTION; ADDICTION AB Background Reducing added sugars intake is one, of the Healthy People 2020 objectives. High added sugars intake may be associated with adverse health consequences. Objective This cross-sectional study identified sociodemographic and behavioral characteristics associated With added sugars intake among US adults (18 years and older) using the 2010 National Health Interview Survey data (n=24,967). Methods The outcome variable was added sugars intake from foods and beverages using scoring algorithms to convert dietary screener frequency responses on nine items to estimates of individual dietary intake of added sugars in teaspoons per day. Added sugars intake was categorized into tertiles (lowest, middle, highest) stratified by sex. The explanatory variables were sociodemographic and behavioral characteristics. Multinomial logistic regression was used to estimate the adjusted odds ratios for the highest and middle tertile added sugars intake groups as compared with the lowest tertile group. Results Estimated median added sugars intake was 17.6 tsp/d for men and 11.7 tsp/d for women. For men and women, those who had significantly greater odds for being in the highest tertile of added sugars intake (men: >= 22.0 tsp/d; women: >= 14.6 tsp/d) were younger, less educated, had lower income, were less physically active, were current smokers, and were former or current infrequent/light drinkers, whereas non-Hispanic other/multiracial and those living in the West had significantly lower odds for being in the highest tertile of added sugars intake. Different patterns were found by sex. Non-Hispanic black men had lower odds for being in the highest tertile of added sugars intake, whereas non-Hispanic black women had greater odds for being in the highest tertile. Conclusions One in three men consumed >= 22.0 tsp added sugars and one in three women consumed >= 14.6 tsp added sugars daily. Higher added sugars intake was associated with various sociodemographic and behavioral characteristics; this information can inform efforts to design programs and policies specific to high-intake populations. C1 [Park, Sohyun; Pan, Liping; Galuska, Deborah A.; Blanck, Heidi M.] Ctr Dis Control & Prevent, Div Nutr Phys Act & Obes, Natl Ctr Chron Dis Prevent & Hlth Promot, 4770 Buford Hwy NE,Mailstop F77, Atlanta, GA 30341 USA. [McGuire, Lisa C.] Ctr Dis Control & Prevent, Div Populat Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. [Thompson, Frances E.] NCI, Risk Factor Assessment Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci,NIH, Bethesda, MD 20892 USA. RP Park, S (reprint author), Ctr Dis Control & Prevent, Div Nutr Phys Act & Obes, Natl Ctr Chron Dis Prevent & Hlth Promot, 4770 Buford Hwy NE,Mailstop F77, Atlanta, GA 30341 USA. EM spark3@cdc.gov FU Intramural CDC HHS [CC999999] NR 36 TC 0 Z9 0 U1 8 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-2672 EI 2212-2680 J9 J ACAD NUTR DIET JI J. Acad. Nutr. Diet. PD OCT PY 2016 VL 116 IS 10 BP 1589 EP 1598 DI 10.1016/j.jand.2016.04.012 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DY4GI UT WOS:000385056600008 PM 27236642 ER PT J AU Lu, GY Ren, L Kolagunda, A Wang, XL Turkbey, IB Choyke, PL Kambhamettu, C AF Lu, Guoyu Ren, Li Kolagunda, Abhishek Wang, Xiaolong Turkbey, Ismail B. Choyke, Peter L. Kambhamettu, Chandra TI Representing 3D shapes based on implicit surface functions learned from RBF neural networks SO JOURNAL OF VISUAL COMMUNICATION AND IMAGE REPRESENTATION LA English DT Article DE 3D shape presentation; Radial basis function; Neural network; 3D reconstruction ID RECONSTRUCTION; KERNELS AB We propose to represent the shape of 3D objects using a neural network classifier. The 3D shape is learned from a neural network, where Radial Basis Function (RBF) is applied as the activation function for each perceptron. The implicit functions derived from the neural network is a combination of radial basis functions, which can represent complex shapes. The use of RBF provides a rotation, translation and scaling invariant feature to represent the shape. We conduct experiments on a new prostate dataset and public datasets. Our testing results show that our neural network -based method can accurately represent various shapes. (C) 2016 Elsevier Inc. All rights reserved. C1 [Lu, Guoyu; Ren, Li; Kolagunda, Abhishek; Wang, Xiaolong; Kambhamettu, Chandra] Univ Delaware, Dept Comp & Informat Sci, Newark, DE 19716 USA. [Turkbey, Ismail B.; Choyke, Peter L.] NCI, NIH, Bethesda, MD 20892 USA. RP Lu, GY (reprint author), Univ Delaware, Dept Comp & Informat Sci, Newark, DE 19716 USA. EM luguoyu@udel.edu NR 35 TC 0 Z9 0 U1 5 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-3203 EI 1095-9076 J9 J VIS COMMUN IMAGE R JI J. Vis. Commun. Image Represent. PD OCT PY 2016 VL 40 BP 852 EP 860 DI 10.1016/j.jvcir.2016.08.014 PN B PG 9 WC Computer Science, Information Systems; Computer Science, Software Engineering SC Computer Science GA DX5CY UT WOS:000384398600039 ER PT J AU Brown, P AF Brown, Patricia TI A Word from OLAW SO LAB ANIMAL LA English DT Editorial Material C1 [Brown, Patricia] NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA. RP Brown, P (reprint author), NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0093-7355 EI 1548-4475 J9 LAB ANIMAL JI Lab Anim. PD OCT PY 2016 VL 45 IS 10 BP 356 EP 356 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA DY4FU UT WOS:000385055200016 PM 27654683 ER PT J AU Blankenship-Paris, TL Dutton, JW Goulding, DR Mcgee, CA Kissling, GE Myers, PH AF Blankenship-Paris, Terry L. Dutton, John W. Goulding, David R. McGee, Christopher A. Kissling, Grace E. Myers, Page H. TI Evaluation of buprenorphine hydrochloride Pluronica (R) gel formulation in male C57BL/6NCrl mice SO LAB ANIMAL LA English DT Article ID SUSTAINED-RELEASE BUPRENORPHINE; RATS RATTUS-NORVEGICUS; ORALLY-ADMINISTERED BUPRENORPHINE; CORTICOSTERONE LEVELS; POSTOPERATIVE ANALGESICS; VOLUNTARY INGESTION; INCISIONAL PAIN; DRUG-RELEASE; BODY-WEIGHT; 2 STRAINS AB Providing adequate analgesia while minimizing handling and stress post-surgery can be challenging. Recently, there have been commercial products made available for providing long acting analgesia in rodents. However, we find there are limitations for use in mice due to the viscosity of the product and the small dosing volumes needed. This project evaluated an in-house compounded formulation of buprenorphine easily made in the laboratory using pharmaceutical. grade products. The release of buprenorphine was evaluated when compounded with two types of hydrogels (Pluronic (R) F-127 and F-68). Mice given buprenorphine in hydrogel (BP) demonstrated higher serum levels of buprenorphine for a longer period of time compared to mice given standard buprenorphine (Bup). However, the rate of decline in serum levels between the groups was similar; thus, it is more likely that the higher buprenorphine concentration seen in the BP group is due to the higher dose of buprenorphine given, rather than a slower release of product. Feed consumption was decreased in both groups one day after dosing; however, there was no difference in body weights. Increased activity in the open field was observed with both buprenorphine formulations, and lipemia was observed in mice given BP which persisted to at least 96 h. Based on our results, we conclude that this formulation did not sustain the release of buprenorphine or eliminate the increased activity commonly seen in mice given buprenorphine. In addition, the lipemia may confound research parameters, especially in cardiac studies and lipid metabolism studies. Therefore, we cannot recommend this formulation for use. C1 [Blankenship-Paris, Terry L.; Goulding, David R.; McGee, Christopher A.; Myers, Page H.] NIEHS, Vet Med Sect, Comparat Med Branch, NIH,DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. [Dutton, John W.] Texas Biomed Res Inst, Southwest Natl Primate Res Ctr, San Antonio, TX USA. [Kissling, Grace E.] NIEHS, Biostat & Computat Biol Branch, NIH, DHHS, Res Triangle Pk, NC USA. RP Blankenship-Paris, TL (reprint author), NIEHS, Vet Med Sect, Comparat Med Branch, NIH,DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM blanken1@niehs.nih.gov FU Intramural Research Program of the National Institutes of Health; National Institute of Environmental Health Sciences FX This research was supported by the Intramural Research Program of the National Institutes of Health and the National Institute of Environmental Health Sciences. This article may be the work product of an employee or group of employees of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), however, the statements, opinions or conclusions contained herein do not necessarily represent the statements, opinions or conclusions of NIEHS, NIH or the United States government. NR 66 TC 0 Z9 0 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0093-7355 EI 1548-4475 J9 LAB ANIMAL JI Lab Anim. PD OCT PY 2016 VL 45 IS 10 BP 370 EP 379 PG 10 WC Veterinary Sciences SC Veterinary Sciences GA DY4FU UT WOS:000385055200021 PM 27654688 ER PT J AU Johnson, C Pinal-Fernandez, I Parikh, R Paik, J Albayda, J Mammen, AL Christopher-Stine, L Danoff, S AF Johnson, Cheilonda Pinal-Fernandez, Iago Parikh, Radhika Paik, Julie Albayda, Jemima Mammen, Andrew L. Christopher-Stine, Lisa Danoff, Sonye TI Assessment of Mortality in Autoimmune Myositis With and Without Associated Interstitial Lung Disease SO LUNG LA English DT Article DE Survival; Interstitial lung disease; Idiopathic inflammatory myopathy; Dermatomyositis; Polymyositis; Clinically amyopathic dermatomyositis ID IDIOPATHIC INFLAMMATORY MYOPATHIES; AMYOPATHIC DERMATOMYOSITIS; POLYMYOSITIS; SURVIVAL; TERM AB Among patients with autoimmune myositis, associated interstitial lung disease (MA-ILD) is a known contributor of excess morbidity and mortality. Recent data on survival in idiopathic inflammatory myopathies originate primarily in Asia and Europe and vary widely. We sought to examine mortality in a large U.S. myositis cohort focusing in particular on the impact of associated ILD. A cross-sectional analysis of participants from the Johns Hopkins Myositis Center with autoimmune myositis (polymyositis [PM], dermatomyositis [DM], or clinically amyopathic dermatomyositis [CADM]) was conducted. The primary outcome assessed was all-cause mortality. Cumulative mortality rates were estimated using the Kaplan-Meier test; the Cox proportional hazards model was used to compare group differences in survival. Eight hundred and thirty-one participants were included with a median follow-up time of 4.5 years. Four hundred thirty-eight (53 %) had PM, 362 (43 %) had DM, and 31 (4 %) had CADM. Ninety-four (11 %) participants had clinically evident ILD. Overall, 51 participants died (6 %). In those without ILD, the survival rates at 1, 5, and 10 years were 99, 95, and 90 %, respectively. In those with ILD, the survival rates at 1, 5, and 10 years were 97, 91, and 81 %, respectively. The risk of death was statistically significantly higher among participants with ILD compared to those without ILD (HR 2.13. 95 % CI 1.06-4.25; p = 0.03). We analyzed one of the largest known cohorts of patients with autoimmune myositis and found significantly higher mortality rates among those with clinically evident ILD compared to those without clinically evident ILD. Our results suggest that ILD remains an important and significant source of mortality in patients with inflammatory myopathies and as such should be screened for and treated aggressively. C1 [Johnson, Cheilonda; Danoff, Sonye] Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, 1830 E Monument St Suite 500, Baltimore, MD 21224 USA. [Pinal-Fernandez, Iago; Mammen, Andrew L.] NIAMSD, Muscle Dis Unit, Lab Muscle Stem Cells & Gene Express, NIH, Bethesda, MD 20892 USA. [Parikh, Radhika] Univ Vermont, Div Pulm & Crit Care Med, Med Ctr, Burlington, VT 05401 USA. [Paik, Julie; Albayda, Jemima; Christopher-Stine, Lisa] Johns Hopkins Univ, Div Rheumatol, Sch Med, Baltimore, MD 21224 USA. [Mammen, Andrew L.] Johns Hopkins Univ, Dept Neurol, Sch Med, Baltimore, MD 21224 USA. RP Danoff, S (reprint author), Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, 1830 E Monument St Suite 500, Baltimore, MD 21224 USA. EM sdanoff@jhmi.edu FU Huayi and Siuling Zhang Discovery Fund FX This study was financially supported by The Huayi and Siuling Zhang Discovery Fund. NR 25 TC 2 Z9 2 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0341-2040 EI 1432-1750 J9 LUNG JI Lung PD OCT PY 2016 VL 194 IS 5 BP 733 EP 737 DI 10.1007/s00408-016-9896-x PG 5 WC Respiratory System SC Respiratory System GA DY5OG UT WOS:000385148500004 PM 27166633 ER PT J AU Fulton, JE Carlson, SA Ainsworth, BE Berrigan, D Carlson, C Dorn, JM Heath, GW Kohl, HW Lee, IM Lee, SM Masse, LC Morrow, JR Gabriel, KP Pivarnik, JM Pronk, NP Rodgers, AB Saelens, BE Sallis, JF Troiano, RP Tudor-Locke, C Wendel, A AF Fulton, Janet E. Carlson, Susan A. Ainsworth, Barbara E. Berrigan, David Carlson, Cynthia Dorn, Joan M. Heath, Gregory W. Kohl, Harold W., III Lee, I-Min Lee, Sarah M. Masse, Louise C. Morrow, James R., Jr. Gabriel, Kelley Pettee Pivarnik, James M. Pronk, Nicolaas P. Rodgers, Anne B. Saelens, Brian E. Sallis, James F. Troiano, Richard P. Tudor-Locke, Catrine Wendel, Arthur TI Strategic Priorities for Physical Activity Surveillance in the United States SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE POPULATION HEALTH; MONITORING; EPIDEMIOLOGY; RECOMMENDATIONS; EXERCISE ID GOOGLE STREET VIEW; NEIGHBORHOOD ENVIRONMENTS; SELF-REPORT; SEDENTARY BEHAVIOR; ADULTS; ACCELEROMETER; PREVALENCE; FITNESS; TRENDS; AUDIT AB Purpose Develop strategic priorities to guide future physical activity surveillance in the United States. Methods The Centers for Disease Control and Prevention and the American College of Sports Medicine convened a scientific roundtable of physical activity and measurement experts. Participants summarized the current state of aerobic physical activity surveillance for adults, focusing on practice and research needs in three areas: 1) behavior, 2) human movement, and 3) community supports. Needs and challenges for each area were identified. At the conclusion of the meeting, experts identified one overarching strategy and five strategic priorities to guide future surveillance. Results The identified overarching strategy was to develop a national plan for physical activity surveillance similar to the U.S. National Physical Activity Plan for promotion. The purpose of the plan would be to enhance coordination and collaboration within and between sectors, such as transportation and public health, and to address specific strategic priorities identified at the roundtable. These strategic priorities were used 1) to identify and prioritize physical activity constructs; 2) to assess the psychometric properties of instruments for physical activity surveillance; 3) to provide training and technical assistance for those collecting, analyzing, or interpreting surveillance data; 4) to explore accessing data from alternative sources; and 5) to improve communication, translation, and dissemination about estimates of physical activity from surveillance systems. Conclusion This roundtable provided strategic priorities for physical activity surveillance in the United States. A first step is to develop a national plan for physical activity surveillance that would provide an operating framework from which to execute these priorities. C1 [Fulton, Janet E.; Carlson, Susan A.; Dorn, Joan M.; Lee, Sarah M.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Ainsworth, Barbara E.] Arizona State Univ, Phoenix, AZ USA. [Berrigan, David; Troiano, Richard P.] NCI, Bethesda, MD 20892 USA. [Carlson, Cynthia] Merrimack Coll, N Andover, MA 01845 USA. [Carlson, Cynthia] MA England Coll, Henniker, NH USA. [Heath, Gregory W.] Univ Tennessee, Chattanooga, TN USA. [Kohl, Harold W., III; Gabriel, Kelley Pettee] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Austin Reg Campus, Austin, TX USA. [Kohl, Harold W., III] Univ Texas Austin, Austin, TX 78712 USA. [Lee, I-Min; Pronk, Nicolaas P.] Harvard Univ, Boston, MA 02115 USA. [Masse, Louise C.] Univ British Columbia, Vancouver, BC, Canada. [Masse, Louise C.] British Columbia Childrens Hosp, Child & Family Res Inst, Vancouver, BC, Canada. [Morrow, James R., Jr.] Univ North Texas, Denton, TX USA. [Pivarnik, James M.] Michigan State Univ, E Lansing, MI 48824 USA. [Pronk, Nicolaas P.] HealthPartners, Minneapolis, MN USA. [Rodgers, Anne B.] Ctr Dis Control & Prevent, Falls Church, VA USA. [Saelens, Brian E.] Univ Washington, Seattle, WA 98195 USA. [Saelens, Brian E.] Seattle Childrens Res Inst, Seattle, WA USA. [Sallis, James F.] Univ Calif Calif, La Jolla, CA USA. [Tudor-Locke, Catrine] Univ Massachusetts, Amherst, MA 01003 USA. [Wendel, Arthur] Agcy Tox Subst & Dis Registry, Atlanta, GA USA. RP Fulton, JE (reprint author), Ctr Dis Control & Prevent, Div Nutr Phys Act & Obes, 4770 Buford Highway NE,MS F-77, Atlanta, GA 30341 USA. EM jkf2@cdc.gov FU Child and Family Research Institute at the British Columbia Children's Hospital FX LCM received salary support from the Child and Family Research Institute at the British Columbia Children's Hospital. NR 68 TC 1 Z9 1 U1 7 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD OCT PY 2016 VL 48 IS 10 BP 2057 EP 2069 DI 10.1249/MSS.0000000000000989 PG 13 WC Sport Sciences SC Sport Sciences GA DX3TZ UT WOS:000384298800024 PM 27187094 ER PT J AU Esmail, H Lai, RP Lesosky, M Wilkinson, KA Graham, CM Coussens, AK Oni, T Warwick, JM Said-Hartley, Q Koegelenberg, CF Walzl, G Flynn, JL Young, DB Barry, CE O'Garra, A Wilkinson, RJ AF Esmail, Hanif Lai, Rachel P. Lesosky, Maia Wilkinson, Katalin A. Graham, Christine M. Coussens, Anna K. Oni, Tolu Warwick, James M. Said-Hartley, Qonita Koegelenberg, Coenraad F. Walzl, Gerhard Flynn, JoAnne L. Young, Douglas B. Barry, Clifton E., III O'Garra, Anne Wilkinson, Robert J. TI Characterization of progressive HIV-associated tuberculosis using 2-deoxy-2-[F-18] fluoro-D-glucose positron emission and computed tomography SO NATURE MEDICINE LA English DT Article ID PULMONARY TUBERCULOSIS; ACTIVE TUBERCULOSIS; FUTURE-PROSPECTS; INFECTION; PREVALENCE; STRATEGIES; DISEASE; ADULTS; LUNG AB Tuberculosis is classically divided into states of latent infection and active disease. Using combined positron emission and computed tomography in 35 asymptomatic, antiretroviral-therapy-naive, HIV-1-infected adults with latent tuberculosis, we identified ten individuals with pulmonary abnormalities suggestive of subclinical, active disease who were substantially more likely to progress to clinical disease. Our findings challenge the conventional two-state paradigm and may aid future identification of biomarkers that are predictive of progression. C1 [Esmail, Hanif; Young, Douglas B.; Wilkinson, Robert J.] Imperial Coll London, Dept Med, London, England. [Esmail, Hanif; Lesosky, Maia; Wilkinson, Katalin A.; Coussens, Anna K.; Oni, Tolu; Barry, Clifton E., III; Wilkinson, Robert J.] Univ Cape Town, Inst Infect Dis & Mol Med, Clin Infect Dis Res Initiat, Cape Town, South Africa. [Esmail, Hanif] Univ Oxford, Radcliffe Dept Med, Oxford, England. [Lai, Rachel P.; Wilkinson, Katalin A.; Graham, Christine M.; Young, Douglas B.; O'Garra, Anne; Wilkinson, Robert J.] Francis Crick Inst Mill Hill Lab, London, England. [Lesosky, Maia] Univ Cape Town, Sch Publ Hlth & Family Med, Div Epidemiol & Biostat, Cape Town, South Africa. [Warwick, James M.] Univ Stellenbosch, Dept Med Imaging & Clin Oncol, Cape Town, South Africa. [Said-Hartley, Qonita] Groote Schuur Hosp, Dept Radiol, Cape Town, South Africa. [Koegelenberg, Coenraad F.; Walzl, Gerhard] Univ Stellenbosch, Dept Med, Cape Town, South Africa. [Walzl, Gerhard; Barry, Clifton E., III] Univ Stellenbosch, Dept Biomed Sci, Fac Med & Hlth Sci, Cape Town, South Africa. [Flynn, JoAnne L.] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA USA. [Barry, Clifton E., III] NIAID, TB Res Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Barry, Clifton E., III] Univ Cape Town, Dept Pathol, Cape Town, South Africa. [O'Garra, Anne] Imperial Coll London, Natl Heart & Lung Inst, London, England. RP Esmail, H; Wilkinson, RJ (reprint author), Imperial Coll London, Dept Med, London, England.; Esmail, H; Wilkinson, RJ (reprint author), Univ Cape Town, Inst Infect Dis & Mol Med, Clin Infect Dis Res Initiat, Cape Town, South Africa.; Esmail, H (reprint author), Univ Oxford, Radcliffe Dept Med, Oxford, England.; Wilkinson, RJ (reprint author), Francis Crick Inst Mill Hill Lab, London, England. EM hanif.esmail@ndcls.ox.ac.uk; r.j.wilkinson@imperial.ac.uk OI Esmail, Hanif/0000-0002-4278-9316; Lesosky, Maia/0000-0002-2026-958X; Coussens, Anna/0000-0002-7086-2621 FU Wellcome Trust [090170, 104803]; Bill and Melinda Gates Foundation-Wellcome Trust Grand challenges in Global Health [37822]; US National Institutes of Health (NIH) [R01 HL106804]; intramural research program of the NIH-NIAID; European Union [FP& HEALTH F3-2012-305578]; National Research Foundation of South Africa [96841]; Research Councils of the UK via the Francis Crick Institute [10218, U117565642]; Medical Research Council of South Africa (Strategic Health Innovations partnership) FX This work was funded by the Wellcome Trust (grant no. 090170 (H.E.) and 104803 (R.J.W.)), the Bill and Melinda Gates Foundation-Wellcome Trust Grand challenges in Global Health (grant no. 37822; D.B.Y.), the US National Institutes of Health (NIH) (grant no. R01 HL106804; J.L.F.) and the intramural research program of the NIH-NIAID (C.E.B.). R.J.W. also received support from the European Union (grant no. FP& HEALTH F3-2012-305578), the National Research Foundation of South Africa (grant no. 96841), the Research Councils of the UK via the Francis Crick Institute (grant no. 10218 and U117565642) and the Medical Research Council of South Africa (Strategic Health Innovations partnership). NR 20 TC 5 Z9 5 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD OCT PY 2016 VL 22 IS 10 BP 1090 EP 1093 DI 10.1038/nm.4161 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA DY1RQ UT WOS:000384872500011 PM 27595321 ER PT J AU Malherbe, ST Shenai, S Ronacher, K Loxton, AG Dolganov, G Kriel, M Van, T Chen, RY Warwick, J Via, LE Song, T Lee, M Schoolnik, G Tromp, G Alland, D Barry, CE Winter, J Walzl, G AF Malherbe, Stephanus T. Shenai, Shubhada Ronacher, Katharina Loxton, Andre G. Dolganov, Gregory Kriel, Magdalena Tran Van Chen, Ray Y. Warwick, James Via, Laura E. Song, Taeksun Lee, Myungsun Schoolnik, Gary Tromp, Gerard Alland, David Barry, Clifton E., III Winter, Jill Walzl, Gerhard CA Catalysis TB-Biomarker Consortium TI Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure SO NATURE MEDICINE LA English DT Article ID PULMONARY TUBERCULOSIS; RECURRENT TUBERCULOSIS; THERAPEUTIC RESPONSE; SHORTENING TREATMENT; COMPUTED-TOMOGRAPHY; CULTURE CONVERSION; RISK-FACTORS; RELAPSE; REINFECTION; IMPAIRMENT AB The absence of a gold standard to determine when antibiotics induce a sterilizing cure has confounded the development of new approaches to treat pulmonary tuberculosis (PTB). We detected positron emission tomography and computerized tomography (PET-CT) imaging response patterns consistent with active disease, along with the presence of Mycobacterium tuberculosis (MTB) mRNA in sputum and bronchoalveolar lavage samples, in a substantial proportion of adult, HIV-negative patients with PTB after a standard 6-month treatment plus 1 year follow-up, including patients with a durable cure and others who later developed recurrent disease. The presence of MTB mRNA in the context of nonresolving and intensifying lesions on PET-CT images might indicate ongoing transcription, suggesting that even apparently curative treatment for PTB may not eradicate all of the MTB bacteria in most patients. This suggests an important complementary role for the immune response in maintaining a disease-free state. Sterilizing drugs or host-directed therapies, and better treatment response markers, are probably needed for the successful development of improved and shortened PTB-treatment strategies. C1 [Malherbe, Stephanus T.; Ronacher, Katharina; Loxton, Andre G.; Kriel, Magdalena; Tromp, Gerard; Barry, Clifton E., III; Walzl, Gerhard] Univ Stellenbosch, Natl Res Fdn Ctr Excellence Biomed TB Res, Dept Sci & Technol, Cape Town, South Africa. [Malherbe, Stephanus T.; Ronacher, Katharina; Loxton, Andre G.; Kriel, Magdalena; Tromp, Gerard; Barry, Clifton E., III; Walzl, Gerhard] Univ Stellenbosch, Fac Med & Hlth Sci, Div Mol Biol & Human Genet, South African Med Res Council,Ctr TB Res, Cape Town, South Africa. [Shenai, Shubhada] Rutgers New Jersey Med Sch, Dept Med, Ctr Emerging Pathogens, Newark, NJ USA. [Dolganov, Gregory; Tran Van] Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA. [Chen, Ray Y.; Via, Laura E.] NIAID, TB Res Sect, Lab Clin Infect Dis, Div Intramural Res,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Warwick, James] Tygerberg Acad Hosp, Western Cape Acad Positron Emiss Tomog Computed T, Cape Town, South Africa. [Warwick, James] Univ Stellenbosch, Div Nucl Med, Dept Med Imaging & Clin Oncol, Fac Med & Hlth Sci, Cape Town, South Africa. [Via, Laura E.; Barry, Clifton E., III] Univ Cape Town, Inst Infect Dis & Mol Med, Dept Clin Lab Sci, Cape Town, South Africa. [Song, Taeksun; Lee, Myungsun] Int TB Res Ctr, Seoul, South Korea. [Winter, Jill] Catalysis Fdn Hlth, Emeryville, CA USA. Natl Med Ctr, Seoul, South Korea. NIAID, Biostat Res Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. Univ Stellenbosch, Divis Pulmonol, Fac Med & Hlth Sci, Cape Town, South Africa. Univ Stellenbosch, Fac Med & Hlth Sci, Med Imaging & Clin Oncol, Div Radiodiag, Cape Town, South Africa. RP Malherbe, ST (reprint author), Univ Stellenbosch, Natl Res Fdn Ctr Excellence Biomed TB Res, Dept Sci & Technol, Cape Town, South Africa.; Malherbe, ST (reprint author), Univ Stellenbosch, Fac Med & Hlth Sci, Div Mol Biol & Human Genet, South African Med Res Council,Ctr TB Res, Cape Town, South Africa. EM malherbe@sun.ac.za FU Catalysis Foundation for Health (CFH); Division of Intramural Research, National Institute of Allergy and Infectious Diseases; National Institute of Allergy and Infectious Diseases, International Collaborations in Infectious Disease Research FX Funding was provided by grants from the Catalysis Foundation for Health (CFH) (G.W., C.E.B. and D.A.) the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (C.E.B.) and the National Institute of Allergy and Infectious Diseases, International Collaborations in Infectious Disease Research (G.W.), as well as by a bursary from the South African National Research Fund and the Medical Research Council's Clinician Scholarship Program (S.T.M.). We thank our participants for their willingness to take part in this study. We acknowledge R. Thayer and M. Urdea of CFH, the staff at the Stellenbosch University Immunology Research Group, the International TB Research Center (Seoul), the Western Cape Academic PET-CT Centre, Ithemba LABS, Tygerberg Academic Hospital's Nuclear Medicine Department and Pulmonology Unit, as well as the managers and healthcare providers from the City of Cape Town Health Department for assistance with the recruitment of participants and sample collection. NR 52 TC 3 Z9 3 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD OCT PY 2016 VL 22 IS 10 BP 1094 EP 1100 DI 10.1038/nm.4177 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA DY1RQ UT WOS:000384872500012 PM 27595324 ER PT J AU Xu, M Lee, EM Wen, ZX Cheng, YC Huang, WK Qian, XY Julia, TCW Kouznetsova, J Ogden, SC Hammack, C Jacob, F Nguyen, HN Itkin, M Hanna, C Shinn, P Allen, C Michael, SG Simeonov, A Huang, WW Christian, KM Goate, A Brennand, KJ Huang, RL Xia, MH Ming, GL Zheng, W Song, HJ Tang, HL AF Xu, Miao Lee, Emily M. Wen, Zhexing Cheng, Yichen Huang, Wei-Kai Qian, Xuyu Julia, T. C. W. Kouznetsova, Jennifer Ogden, Sarah C. Hammack, Christy Jacob, Fadi Ha Nam Nguyen Itkin, Misha Hanna, Catherine Shinn, Paul Allen, Chase Michael, Samuel G. Simeonov, Anton Huang, Wenwei Christian, Kimberly M. Goate, Alison Brennand, Kristen J. Huang, Ruili Xia, Menghang Ming, Guo-li Zheng, Wei Song, Hongjun Tang, Hengli TI Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen SO NATURE MEDICINE LA English DT Article ID CDK9 INHIBITORS; APPROVED DRUGS; MICE; TRANSMISSION; REPLICATION; ORGANOIDS; NICLOSAMIDE; THERAPY; FIT-039; BIOLOGY AB In response to the current global health emergency posed by the Zika virus (ZIKV) outbreak and its link to microcephaly and other neurological conditions, we performed a drug repurposing screen of similar to 6,000 compounds that included approved drugs, clinical trial drug candidates and pharmacologically active compounds; we identified compounds that either inhibit ZIKV infection or suppress infection-induced caspase-3 activity in different neural cells. A pan-caspase inhibitor, emricasan, inhibited ZIKV-induced increases in caspase-3 activity and protected human cortical neural progenitors in both monolayer and three-dimensional organoid cultures. Ten structurally unrelated inhibitors of cyclin-dependent kinases inhibited ZIKV replication. Niclosamide, a category B anthelmintic drug approved by the US Food and Drug Administration, also inhibited ZIKV replication. Finally, combination treatments using one compound from each category (neuroprotective and antiviral) further increased protection of human neural progenitors and astrocytes from ZIKV-induced cell death. Our results demonstrate the efficacy of this screening strategy and identify lead compounds for anti-ZIKV drug development. C1 [Xu, Miao; Kouznetsova, Jennifer; Itkin, Misha; Shinn, Paul; Michael, Samuel G.; Simeonov, Anton; Huang, Wenwei; Huang, Ruili; Xia, Menghang; Zheng, Wei] NIH, Natl Ctr Adv Translat, Bldg 10, Bethesda, MD 20892 USA. [Xu, Miao] Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Hangzhou, Zhejiang, Peoples R China. [Lee, Emily M.; Cheng, Yichen; Ogden, Sarah C.; Hammack, Christy; Hanna, Catherine; Allen, Chase; Tang, Hengli] Florida State Univ, Dept Biol Sci, B-157, Tallahassee, FL 32306 USA. [Wen, Zhexing] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. [Wen, Zhexing] Emory Univ, Sch Med, Dept Cell Biol, Atlanta, GA USA. [Wen, Zhexing] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Wen, Zhexing; Huang, Wei-Kai; Qian, Xuyu; Jacob, Fadi; Ha Nam Nguyen; Christian, Kimberly M.; Ming, Guo-li; Song, Hongjun] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21218 USA. [Huang, Wei-Kai] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Qian, Xuyu; Ming, Guo-li; Song, Hongjun] Johns Hopkins Univ, Sch Med, Biomed Engn Grad Program, Baltimore, MD 21218 USA. [Julia, T. C. W.; Goate, Alison] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Jacob, Fadi; Ming, Guo-li; Song, Hongjun] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21218 USA. [Ha Nam Nguyen; Christian, Kimberly M.; Ming, Guo-li; Song, Hongjun] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Brennand, Kristen J.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Ming, Guo-li] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Ming, Guo-li; Song, Hongjun] Johns Hopkins Univ, Sch Med, Kavli Neurosci Discovery Inst, Baltimore, MD 21218 USA. RP Zheng, W (reprint author), NIH, Natl Ctr Adv Translat, Bldg 10, Bethesda, MD 20892 USA.; Tang, HL (reprint author), Florida State Univ, Dept Biol Sci, B-157, Tallahassee, FL 32306 USA.; Ming, GL; Song, HJ (reprint author), Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21218 USA.; Ming, GL; Song, HJ (reprint author), Johns Hopkins Univ, Sch Med, Biomed Engn Grad Program, Baltimore, MD 21218 USA.; Song, HJ (reprint author), Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21218 USA.; Ming, GL; Song, HJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.; Ming, GL (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.; Ming, GL; Song, HJ (reprint author), Johns Hopkins Univ, Sch Med, Kavli Neurosci Discovery Inst, Baltimore, MD 21218 USA. EM gming1@jhmi.edu; wzheng@mail.nih.gov; shongju1@jhmi.edu; tang@bio.fsu.edu RI Brennand, Kristen/J-8704-2012; Zheng, Wei/J-8889-2014; OI Brennand, Kristen/0000-0003-0993-5956; Zheng, Wei/0000-0003-1034-0757; Qian, Xuyu/0000-0001-5944-3816 FU Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health (NIH); Florida State University; Emory University; Brain and Behavior Research Foundation; New York Stem Cell Foundation; Maryland Stem Cell Research Fund; Simons Foundation Autism Research Initiative [308988]; NIH [NS048271, NS095348, MH105128, NS047344, NS097206, MH106434, MH101454, MH106056, AG005138, AG046170, AI119530] FX We thank R. Tesh and P.-Y. Shi (University of Texas Medical Branch) and the World Reference Center for Emerging Viruses and Arboviruses (WRCEVA) for the FSS-13025 isolate of ZIKV, and D. Meckes (Florida State University) for the glioblastoma SNB-19 cell line. We also thank L. Liu and Y. Cai for technical support. This work was supported by the Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health (NIH) (W.Z.), ZIKV seed funding from Florida State University (H.T.), a start-up fund from Emory University (Z.W.), the Brain and Behavior Research Foundation (K.J.B.), the New York Stem Cell Foundation (K.J.B.), the Maryland Stem Cell Research Fund (G.M. and H.S.), the Simons Foundation Autism Research Initiative (award no. 308988; H.S.), and partially by NIH grants NS048271 (G.M.), NS095348 (G.M.), MH105128 (G.M.), NS047344 (H.S.), NS097206 (H.S.), MH106434 (H.S.), MH101454 (K.J.B.), MH106056 (K.J.B.), AG005138 (K.J.B.), AG046170 (K.J.B.) and AI119530 (H.T.). NR 59 TC 23 Z9 23 U1 121 U2 121 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD OCT PY 2016 VL 22 IS 10 BP 1101 EP 1107 DI 10.1038/nm.4184 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA DY1RQ UT WOS:000384872500013 PM 27571349 ER PT J AU Blackshaw, S Venkataraman, A Irizarry, J Yang, K Anderson, S Campbell, E Gatlin, CL Freeman, NL Basavappa, R Stewart, R Loss, MA Pino, I Zhu, H Bader, JS AF Blackshaw, Seth Venkataraman, Anand Irizarry, Jose Yang, Kun Anderson, Stephen Campbell, Elliot Gatlin, Christine L. Freeman, Nancy L. Basavappa, Ravi Stewart, Randall Loss, Michael A. Pino, Ignacio Zhu, Heng Bader, Joel S. TI The NIH Protein Capture Reagents Program (PCRP): a standardized protein affinity reagent toolbox SO NATURE METHODS LA English DT Letter ID ANTIBODIES C1 [Blackshaw, Seth; Venkataraman, Anand] Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Baltimore, MD 21218 USA. [Blackshaw, Seth] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Blackshaw, Seth] Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD 21218 USA. [Blackshaw, Seth; Zhu, Heng; Bader, Joel S.] Johns Hopkins Univ, Ctr Human Syst Biol, Baltimore, MD 21218 USA. [Blackshaw, Seth] Johns Hopkins Univ, Inst Cell Engn, Baltimore, MD 21218 USA. [Irizarry, Jose; Pino, Ignacio] CDI Labs, Guanajibo Res & Innovat Pk, Mayaguez, PR USA. [Yang, Kun] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA. [Anderson, Stephen; Campbell, Elliot] Rutgers State Univ, Dept Mol Biol & Biochem, New Brunswick, NJ USA. [Anderson, Stephen; Campbell, Elliot] Ctr Adv Biotechnol & Med, Piscataway, NJ USA. [Gatlin, Christine L.] NHGRI, Bethesda, MD 20892 USA. [Gatlin, Christine L.; Freeman, Nancy L.; Basavappa, Ravi; Stewart, Randall] NIH, Bldg 10, Bethesda, MD 20892 USA. [Freeman, Nancy L.] NIDCD, Div Sci Programs, Bethesda, MD USA. [Basavappa, Ravi] NIH, Off Strateg Coordinat, Off Director, Bldg 10, Bethesda, MD 20892 USA. [Stewart, Randall] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Loss, Michael A.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Adv Biomed Comp Ctr, Frederick, MD USA. [Zhu, Heng] Johns Hopkins Univ, Dept Pharmacol, Baltimore, MD USA. [Bader, Joel S.] Ctr Neurosci, Bethesda, MD USA. RP Blackshaw, S (reprint author), Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Baltimore, MD 21218 USA.; Blackshaw, S (reprint author), Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.; Blackshaw, S (reprint author), Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD 21218 USA.; Blackshaw, S (reprint author), Johns Hopkins Univ, Ctr Human Syst Biol, Baltimore, MD 21218 USA.; Blackshaw, S (reprint author), Johns Hopkins Univ, Inst Cell Engn, Baltimore, MD 21218 USA. EM sblack@jhmi.edu NR 6 TC 0 Z9 0 U1 3 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 EI 1548-7105 J9 NAT METHODS JI Nat. Methods PD OCT PY 2016 VL 13 IS 10 BP 805 EP 806 DI 10.1038/nmeth.4013 PG 2 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA DY6CV UT WOS:000385194600005 PM 27684578 ER PT J AU Uhlen, M Bandrowski, A Carr, S Edwards, A Ellenberg, J Lundberg, E Rimm, DL Rodriguez, H Hiltke, T Snyder, M Yamamoto, T AF Uhlen, Mathias Bandrowski, Anita Carr, Steven Edwards, Aled Ellenberg, Jan Lundberg, Emma Rimm, David L. Rodriguez, Henry Hiltke, Tara Snyder, Michael Yamamoto, Tadashi TI A proposal for validation of antibodies SO NATURE METHODS LA English DT Article ID ASSAYS; LOCALIZATION; MICROARRAYS; PROTEINS; CELLS AB We convened an ad hoc International Working Group for Antibody Validation in order to formulate the best approaches for validating antibodies used in common research applications and to provide guidelines that ensure antibody reproducibility. We recommend five conceptual 'pillars' for antibody validation to be used in an application-specific manner. C1 [Uhlen, Mathias; Lundberg, Emma] KTH Royal Inst Technol, Sch Biotechnol, Sci Life Lab, Stockholm, Sweden. [Bandrowski, Anita] Univ Calif San Diego, Ctr Res Biol Syst, San Diego, CA 92103 USA. [Carr, Steven] Broad Inst Massachusetts Inst Technol & Harvard U, Prote Platform, Cambridge, MA USA. [Edwards, Aled] Univ Toronto, Struct Genom Consortium, Toronto, ON, Canada. [Ellenberg, Jan] European Mol Biol Lab, Cell Biol & Biophys Unit, Heidelberg, Germany. [Rimm, David L.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. [Rodriguez, Henry; Hiltke, Tara] NCI, Off Canc Clin Prote Res, NIH, Bethesda, MD 20892 USA. [Snyder, Michael] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA. [Yamamoto, Tadashi] Niigata Univ, Biofluid Biomarker Ctr, Niigata, Japan. RP Uhlen, M (reprint author), KTH Royal Inst Technol, Sch Biotechnol, Sci Life Lab, Stockholm, Sweden. EM mathias.uhlen@scilifelab.se OI Bandrowski, Anita/0000-0002-5497-0243; Ellenberg, Jan/0000-0001-5909-701X; Uhlen, Mathias/0000-0002-4858-8056 NR 20 TC 7 Z9 7 U1 14 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 EI 1548-7105 J9 NAT METHODS JI Nat. Methods PD OCT PY 2016 VL 13 IS 10 BP 823 EP + DI 10.1038/NMETH.3995 PG 6 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA DY6CV UT WOS:000385194600015 PM 27595404 ER PT J AU Arveson, I Shelton, M Tonkura, F Bendixen, R Meilleur, K AF Arveson, I. Shelton, M. Tonkura, F. Bendixen, R. Meilleur, K. TI Development of a proxy motor outcome measurement scale in young children with neuromuscular disorders SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 21st International Congress of the World-Muscle-Society CY OCT 04-08, 2016 CL Granada, SPAIN SP World Muscle Soc C1 [Arveson, I.; Shelton, M.; Tonkura, F.; Meilleur, K.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Bendixen, R.] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 EI 1873-2364 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2016 VL 26 SU 2 MA P.207 BP S148 EP S148 DI 10.1016/j.nmd.2016.06.227 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DY0ME UT WOS:000384790100217 ER PT J AU Arveson, I Witherspoon, J Drinkard, B Waite, M Razaqyar, M Tounkara, E Elliott, J Shelton, M Jain, M Bonnemann, C Meilleur, K AF Arveson, I. Witherspoon, J. Drinkard, B. Waite, M. Razaqyar, M. Tounkara, E. Elliott, J. Shelton, M. Jain, M. Bonnemann, C. Meilleur, K. TI Antioxidant therapy in RYR1-related myopathies SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 21st International Congress of the World-Muscle-Society CY OCT 04-08, 2016 CL Granada, SPAIN SP World Muscle Soc C1 [Arveson, I.; Witherspoon, J.; Drinkard, B.; Waite, M.; Razaqyar, M.; Tounkara, E.; Elliott, J.; Shelton, M.; Jain, M.; Bonnemann, C.; Meilleur, K.] NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 EI 1873-2364 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2016 VL 26 SU 2 MA P.166 BP S137 EP S137 DI 10.1016/j.nmd.2016.06.186 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DY0ME UT WOS:000384790100176 ER PT J AU Bharucha-Goebel, D Collins, J Hu, Y Foley, AR Donkervoort, S Leach, M Dastgir, N Vuillerot, C Meilleur, K Jain, M Waite, M Jacobson, S Gordish, H Rutkowski, A Hoffman, E Hathout, Y Bonnemann, C AF Bharucha-Goebel, D. Collins, J. Hu, Y. Foley, A. Reghan Donkervoort, S. Leach, M. Dastgir, N. Vuillerot, C. Meilleur, K. Jain, M. Waite, M. Jacobson, S. Gordish, H. Rutkowski, A. Hoffman, E. Hathout, Y. Bonnemann, C. TI Serum biomarker discovery for congenital muscular dystrophies SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 21st International Congress of the World-Muscle-Society CY OCT 04-08, 2016 CL Granada, SPAIN SP World Muscle Soc C1 [Bharucha-Goebel, D.; Hu, Y.; Foley, A. Reghan; Donkervoort, S.; Leach, M.; Meilleur, K.; Jain, M.; Waite, M.; Bonnemann, C.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Bharucha-Goebel, D.; Leach, M.] Natl Inst Childrens Natl Hlth Syst, Bethesda, MD USA. [Collins, J.] Mercy Clin, Springfield, MO USA. [Dastgir, N.] Columbia Univ, Med Ctr, New York, NY USA. [Vuillerot, C.] Hosp Civils Lyon, Lyon, France. [Jacobson, S.] Cincinnati Childrens Hosp Ctr, Cincinnati, OH USA. [Gordish, H.] Childrens Natl Hlth Syst, Washington, DC USA. [Rutkowski, A.] Cure CMD, Torrance, CA USA. [Hoffman, E.; Hathout, Y.] Childrens Natl Hlth Syst CRI, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 EI 1873-2364 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2016 VL 26 SU 2 MA P.345 BP S189 EP S189 DI 10.1016/j.nmd.2016.06.374 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DY0ME UT WOS:000384790100363 ER PT J AU Butterfield, R Dunn, D Hu, Y Bonnernann, C Weiss, R AF Butterfield, R. Dunn, D. Hu, Y. Bonnernann, C. Weiss, R. TI Transcriptome profiling identifies key pathways important in collagen VI related muscular dystrophies including differences between patients with dominant negative vs. null mutations SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 21st International Congress of the World-Muscle-Society CY OCT 04-08, 2016 CL Granada, SPAIN SP World Muscle Soc C1 [Butterfield, R.; Dunn, D.; Weiss, R.] Univ Utah, Salt Lake City, UT USA. [Hu, Y.; Bonnernann, C.] NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 EI 1873-2364 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2016 VL 26 SU 2 MA P.342 BP S188 EP S189 DI 10.1016/j.nmd.2016.06.371 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DY0ME UT WOS:000384790100360 ER PT J AU Carrillo, N Huizing, M Quintana, M Slota, C Malicdan, M Khatami, H Berry, S Gahl, W AF Carrillo, N. Huizing, M. Quintana, M. Slota, C. Malicdan, M. Khatami, H. Berry, S. Gahl, W. TI Therapeutic development of ManNAc for GNE myopathy SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 21st International Congress of the World-Muscle-Society CY OCT 04-08, 2016 CL Granada, SPAIN SP World Muscle Soc C1 [Carrillo, N.; Huizing, M.; Slota, C.; Malicdan, M.; Gahl, W.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Quintana, M.; Berry, S.] Berry Consultants, Austin, TX USA. [Khatami, H.] Escala Therapeut, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 EI 1873-2364 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2016 VL 26 SU 2 MA P.283 BP S172 EP S172 DI 10.1016/j.nmd.2016.06.313 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DY0ME UT WOS:000384790100302 ER PT J AU Rubio, RD Martinez, A Poza, J Bragado, FG Jerico, I van der Ven, P Furst, D Romero, N Goldfarb, L Olive, M AF Dominguez Rubio, R. Martinez, A. Poza, J. Garcia Bragado, F. Jerico, I. van der Ven, P. Fuerst, D. Romero, N. Goldfarb, L. Olive, M. TI Intranuclear protein aggregation in myofibrillar myopathies SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 21st International Congress of the World-Muscle-Society CY OCT 04-08, 2016 CL Granada, SPAIN SP World Muscle Soc C1 [Dominguez Rubio, R.; Martinez, A.; Olive, M.] IDIBELL Hosp Bellvitge, Lhospitalet De Llobregat, Spain. [Poza, J.] Hosp Donostia, San Sebastian, Spain. [Garcia Bragado, F.] Hosp Virgen del Camino, Pamplona, Spain. [Jerico, I.] Complejo Hosp Navarra, Pamplona, Spain. [van der Ven, P.; Fuerst, D.] Univ Bonn, Inst Cell Biol, Bonn, Germany. [Romero, N.] GHU Pitie Salpetriere, Inst Myol, Paris, France. [Goldfarb, L.] NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 EI 1873-2364 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2016 VL 26 SU 2 MA P.352 BP S191 EP S191 DI 10.1016/j.nmd.2016.06.381 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DY0ME UT WOS:000384790100370 ER PT J AU Foley, AR Cocanougher, B Flynn, L Yun, P Jain, M Waite, M Vasavada, R de Chastonay, S Donkervoort, S Bonnemann, C AF Foley, A. Reghan Cocanougher, B. Flynn, L. Yun, P. Jain, M. Waite, M. Vasavada, R. de Chastonay, S. Donkervoort, S. Bonnemann, C. TI MTM1-related myopathy carrier females manifest significant skeletal asymmetries and a spectrum of muscle involvement SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 21st International Congress of the World-Muscle-Society CY OCT 04-08, 2016 CL Granada, SPAIN SP World Muscle Soc C1 [Foley, A. Reghan; Flynn, L.; Yun, P.; Donkervoort, S.; Bonnemann, C.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Cocanougher, B.] Howard Hughes Med Inst, Ashburn, VA USA. [Jain, M.; Waite, M.; Vasavada, R.] NIH, Bethesda, MD USA. [de Chastonay, S.] Cure CMD, Torrance, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 EI 1873-2364 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2016 VL 26 SU 2 MA P.93 BP S117 EP S117 DI 10.1016/j.nmd.2016.06.115 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DY0ME UT WOS:000384790100105 ER PT J AU Korinthenberg, R Schorling, D Rost, S Krueger, M Beytia, M Mueller, C Bonnemann, C Kirschner, J AF Korinthenberg, R. Schorling, D. Rost, S. Krueger, M. Beytia, M. Mueller, C. Bonnemann, C. Kirschner, J. TI Severe congenital myopathy with myasthenic features and lethal neurodegeneration - A new ALG14-related phenotype? SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 21st International Congress of the World-Muscle-Society CY OCT 04-08, 2016 CL Granada, SPAIN SP World Muscle Soc C1 [Korinthenberg, R.; Schorling, D.; Krueger, M.; Kirschner, J.] Univ Med Ctr Freiburg, Freiburg, Germany. [Rost, S.; Beytia, M.; Mueller, C.] Univ Wurzburg, D-97070 Wurzburg, Germany. [Bonnemann, C.] NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 EI 1873-2364 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2016 VL 26 SU 2 MA P.77 BP S112 EP S112 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DY0ME UT WOS:000384790100089 ER PT J AU Malicdan, M Leoyklang, P Ciccone, C Carrillo, N Huizing, M Gahl, W AF Malicdan, M. Leoyklang, P. Ciccone, C. Carrillo, N. Huizing, M. Gahl, W. TI GNE myopathy biomarkers: Essential for diagnosis and response to therapy SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 21st International Congress of the World-Muscle-Society CY OCT 04-08, 2016 CL Granada, SPAIN SP World Muscle Soc C1 [Malicdan, M.; Leoyklang, P.; Ciccone, C.; Carrillo, N.; Huizing, M.; Gahl, W.] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 EI 1873-2364 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2016 VL 26 SU 2 MA P.276 BP S170 EP S170 DI 10.1016/j.nmd.2016.06.306 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DY0ME UT WOS:000384790100295 ER PT J AU Miyakawa, M Cho, A Malicdan, M Nishino, I Noguchi, S AF Miyakawa, M. Cho, A. Malicdan, M. Nishino, I. Noguchi, S. TI S-nitrosylation of muscle contractile proteins and metabolic enzymes causes muscle atrophy and weakness in GNE myopathy SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 21st International Congress of the World-Muscle-Society CY OCT 04-08, 2016 CL Granada, SPAIN SP World Muscle Soc C1 [Miyakawa, M.; Nishino, I.; Noguchi, S.] Natl Inst Neurosci, Kodaira, Tokyo, Japan. [Cho, A.] Ewha Womans Univ, Sch Med, Seoul, South Korea. [Malicdan, M.] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 EI 1873-2364 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2016 VL 26 SU 2 MA P.281 BP S171 EP S172 DI 10.1016/j.nmd.2016.06.311 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DY0ME UT WOS:000384790100300 ER PT J AU Oates, E Yau, K Donkervoort, S Swanson, L Brammah, S Topf, A Richard, I Ferreiro, A Hoffman, E Bushby, K Straub, V Udd, B Lek, M MacArthur, D Granzier, H Beggs, A Bonnemann, C North, K Davis, M Laing, N AF Oates, E. Yau, K. Donkervoort, S. Swanson, L. Brammah, S. Topf, A. Richard, I. Ferreiro, A. Hoffman, E. Bushby, K. Straub, V. Udd, B. Lek, M. MacArthur, D. Granzier, H. Beggs, A. Bonnemann, C. North, K. Davis, M. Laing, N. TI Analysis of a large international cohort confirms that recessively inherited loss-of-function TTN mutations cause prenatal or infant-onset muscle disease, often complicated by early cardiorespiratory involvement SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 21st International Congress of the World-Muscle-Society CY OCT 04-08, 2016 CL Granada, SPAIN SP World Muscle Soc C1 [Oates, E.] Inst Neurosci & Muscle Res, Sydney, NSW, Australia. [Yau, K.; Laing, N.] Univ Western Australia, Perth, WA, Australia. [Donkervoort, S.; Bonnemann, C.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Swanson, L.; Beggs, A.] Harvard Med Sch, Boston Childrens Hosp, Boston, MA USA. [Brammah, S.] Concord Repatriat Gen Hosp, Sydney, NSW, Australia. [Topf, A.; Bushby, K.; Straub, V.] Univ Newcastle, Newcastle Upon Tyne, Tyne & Wear, England. [Richard, I.] Genethon, Evry, France. [Ferreiro, A.] Univ Paris, Sorbonne, Diderot, Paris, France. [Hoffman, E.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Hoffman, E.] George Washington Univ, Washington, DC USA. [Udd, B.] Tampere Univ, Tampere, Finland. [Udd, B.] Univ Hosp, Tampere, Finland. [Lek, M.; MacArthur, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lek, M.; MacArthur, D.] Broad Inst Harvard & MIT, Boston, MA USA. [Granzier, H.] Univ Arizona, Tucson, AZ USA. [North, K.] Royal Childrens Hosp, Melbourne, Vic, Australia. [Davis, M.] Royal Perth Hosp, Perth, WA, Australia. RI North, Kathryn/K-6476-2012 OI North, Kathryn/0000-0003-0841-8009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 EI 1873-2364 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2016 VL 26 SU 2 MA S.O.2 BP S89 EP S89 DI 10.1016/j.nmd.2016.06.018 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DY0ME UT WOS:000384790100008 ER PT J AU Punetha, J Kesari, A Hoffman, E Gos, M Kaminska, A Kostera-Pruszczyk, A Hu, Y Zou, Y Bonnemann, C Jedrzejowska, M AF Punetha, J. Kesari, A. Hoffman, E. Gos, M. Kaminska, A. Kostera-Pruszczyk, A. Hu, Y. Zou, Y. Bonnemann, C. Jedrzejowska, M. TI A novel COL12A1 variant expands the clinical picture for a collagen XII-related myopathy SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 21st International Congress of the World-Muscle-Society CY OCT 04-08, 2016 CL Granada, SPAIN SP World Muscle Soc C1 [Punetha, J.; Kesari, A.; Hoffman, E.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Gos, M.] Inst Mother & Child Hlth, Warsaw, Poland. [Kaminska, A.; Kostera-Pruszczyk, A.] Med Univ Warsaw, Warsaw, Poland. [Hu, Y.; Zou, Y.; Bonnemann, C.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Jedrzejowska, M.] Mossakowski Med Res Ctr, Warsaw, Poland. NR 0 TC 0 Z9 0 U1 3 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 EI 1873-2364 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2016 VL 26 SU 2 MA P.344 BP S189 EP S189 DI 10.1016/j.nmd.2016.06.373 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DY0ME UT WOS:000384790100362 ER PT J AU Razaqyar, M Butrum, J Witherspoon, J Tounkara, F Shelton, M Elliott, J Arveson, I Meilleur, K AF Razaqyar, M. Butrum, J. Witherspoon, J. Tounkara, F. Shelton, M. Elliott, J. Arveson, I. Meilleur, K. TI Qualitative comparison of healthy versus affected muscles by ultrasound imaging in RYR1-related myopathies SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 21st International Congress of the World-Muscle-Society CY OCT 04-08, 2016 CL Granada, SPAIN SP World Muscle Soc C1 [Razaqyar, M.; Butrum, J.; Witherspoon, J.; Tounkara, F.; Shelton, M.; Elliott, J.; Arveson, I.; Meilleur, K.] NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 EI 1873-2364 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2016 VL 26 SU 2 MA P.28 BP S98 EP S98 DI 10.1016/j.nmd.2016.06.050 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DY0ME UT WOS:000384790100040 ER PT J AU Witherspoon, J Drinkard, B Arveson, I Stockman, M Jain, M Meilleur, K AF Witherspoon, J. Drinkard, B. Arveson, I. Stockman, M. Jain, M. Meilleur, K. TI Skeletal muscle oxygenation in adults with RYR1-related myopathies: Exploratory study SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 21st International Congress of the World-Muscle-Society CY OCT 04-08, 2016 CL Granada, SPAIN SP World Muscle Soc C1 [Witherspoon, J.; Drinkard, B.; Arveson, I.; Stockman, M.; Jain, M.; Meilleur, K.] NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 EI 1873-2364 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2016 VL 26 SU 2 MA P.160 BP S135 EP S135 DI 10.1016/j.nmd.2016.06.180 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DY0ME UT WOS:000384790100170 ER PT J AU Zou, Y Donkervoort, S Salo, A Barnes, A Hu, Y Foley, AR Makareeva, E Leach, M Dastgir, J Cohn, R DiNonno, W Leikin, S Marini, J Myllyharju, J Bonnemann, C AF Zou, Y. Donkervoort, S. Salo, A. Barnes, A. Hu, Y. Foley, A. Reghan Makareeva, E. Leach, M. Dastgir, J. Cohn, R. DiNonno, W. Leikin, S. Marini, J. Myllyharju, J. Bonnemann, C. TI P4HA1 mutations cause a unique congenital disorder of connective tissue involving tendon, bone, muscle and the eye SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT 21st International Congress of the World-Muscle-Society CY OCT 04-08, 2016 CL Granada, SPAIN SP World Muscle Soc C1 [Zou, Y.; Donkervoort, S.; Hu, Y.; Foley, A. Reghan; Leach, M.; Dastgir, J.; Bonnemann, C.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Salo, A.; Myllyharju, J.] Bioctr Oulu, Oulu Ctr Cell Matrix Res, Oulu, Finland. [Barnes, A.; Makareeva, E.; Leikin, S.; Marini, J.] NICHD, NIH, Bethesda, MD USA. [Cohn, R.] Hosp Sick Children, Toronto, ON, Canada. [DiNonno, W.] Eastern Virginia Med Sch, Norfolk, VA 23501 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 EI 1873-2364 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2016 VL 26 SU 2 MA G.O.21 BP S211 EP S212 DI 10.1016/j.nmd.2016.06.455 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DY0ME UT WOS:000384790100444 ER PT J AU de Jesus, AA Goldbach-Mansky, R AF de Jesus, A. A. Goldbach-Mansky, R. TI Genetically defined autoinflammatory diseases SO ORAL DISEASES LA English DT Review DE autoinflammatory diseases; inflammatory diseases; immune defects; immunology; rheumatology; IL-1; Type I interferon ID FAMILIAL MEDITERRANEAN FEVER; SINGLETON-MERTEN SYNDROME; RECURRENT MULTIFOCAL OSTEOMYELITIS; PEDIATRIC GRANULOMATOUS ARTHRITIS; CONGENITAL SIDEROBLASTIC ANEMIA; MACROPHAGE ACTIVATION SYNDROME; JUVENILE IDIOPATHIC ARTHRITIS; INFLAMMATORY-BOWEL-DISEASE; STEM-CELL TRANSPLANTATION; DEVELOPMENTAL DELAY SIFD AB Autoinflammatory diseases are hyperinflammatory, immune dysregulatory conditions that typically present in early childhood with fever and rashes and disease-specific patterns of organ inflammation. This review provides a historic background of autoinflammatory disease research, an overview of the currently genetically defined autoinflammatory diseases, and insights into treatment strategies derived from understanding of the disease pathogenesis. The integrative assessment of autoinflammatory conditions led to the identification of innate pro-inflammatory cytokine amplification loops' as the cause of the systemic and organ-specific disease manifestations, which initially centered around increased IL-1 production and signaling. More recently, additional innate pro-inflammatory cytokine amplification loops resulting in increased Type I IFN, IL-17, IL-18, or IL-36 signaling or production have led to the successful use of targeted therapies in some of these conditions. Clinical findings such as fever patterns, type of skin lesions, genetic mutation testing, and the prevalent cytokine abnormalities can be used to group autoinflammatory diseases. C1 [de Jesus, A. A.; Goldbach-Mansky, R.] Natl Inst Arthrit Musculoskeletal & Skin Dis NIAM, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD USA. RP Goldbach-Mansky, R (reprint author), Natl Inst Arthrit Musculoskeletal & Skin Dis NIAM, Translat Autoinflammatory Dis Sect, Ctr Clin, NIH, Bldg 10 Room 6D47-B,10 Ctr Dr, Bethesda, MD 20814 USA. EM goldbacr@arb.niams.nih.gov FU Intramural NIH HHS [Z01 AR041138-06] NR 82 TC 0 Z9 0 U1 5 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1354-523X EI 1601-0825 J9 ORAL DIS JI Oral Dis. PD OCT PY 2016 VL 22 IS 7 BP 591 EP 604 DI 10.1111/odi.12448 PG 14 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DW4MS UT WOS:000383617900003 PM 26837051 ER PT J AU Shaikh, N Hoberman, A Keren, R Ivanova, A Ziessman, HA Cui, G Mattoo, TK Bhatnagar, S Nadkarni, MD Moxey-Mims, M Primack, WA AF Shaikh, Nader Hoberman, Alejandro Keren, Ron Ivanova, Anastasia Ziessman, Harvey A. Cui, Gang Mattoo, Tej K. Bhatnagar, Sonika Nadkarni, Milan D. Moxey-Mims, Marva Primack, William A. TI Utility of sedation for young children undergoing dimercaptosuccinic acid renal scans SO PEDIATRIC RADIOLOGY LA English DT Article DE Anxiolytic; Children; Dimercaptosuccinic acid; Renal scintigraphy; Sedation; Ultrasound; Voiding cystourethrogram ID VOIDING CYSTOURETHROGRAPHY; ORAL MIDAZOLAM; VESICOURETERAL REFLUX; NITROUS-OXIDE; DOUBLE-BLIND; DISTRESS; EFFICACY; PREMEDICATION; SAFETY AB No studies have examined whether use of sedation during a Tc-99 m dimercaptosuccinic acid (DMSA) renal scan reduces patient discomfort. To compare discomfort level during a DMSA scan to the discomfort level during other frequently performed uroradiologic tests, and to determine whether use of sedation during a DMSA scan modifies the level of discomfort. We examined the discomfort level in 798 children enrolled in the Randomized Intervention for children with Vesicoureteral Reflux (RIVUR) and Careful Urinary Tract Infection Evaluation (CUTIE) studies by asking parents to rate their child's discomfort level with each procedure on a scale from 0 to 10. We compared discomfort during the DMSA scan and the DMSA image quality between centers in which sedation was used > 90% of the time (sedation centers), centers in which sedation was used < 10% of the time (non-sedation centers), and centers in which sedation was used on a case-by-case basis (selective centers). Mean discomfort level was highest for voiding cystourethrogram (6.4), followed by DMSA (4.0), followed by ultrasound (2.4; P < 0.0001). Mean discomfort level during the DMSA scan was significantly higher at non-sedation centers than at selective centers (P < 0.001). No difference was apparent in discomfort level during the DMSA scan between sedation centers and selective centers (P=0.12), or between the sedation centers and non-sedation centers (P=0.80). There were no differences in the proportion with uninterpretable DMSA scans according to sedation use. Selective use of sedation in children 12-36 months of age can reduce the discomfort level experienced during a DMSA scan. C1 [Shaikh, Nader; Hoberman, Alejandro; Bhatnagar, Sonika] Univ Pittsburgh, Sch Med, Childrens Hosp Pittsburgh UPMC, Div Gen Acad Pediat, One Childrens Hosp Dr,4401 Penn Ave, Pittsburgh, PA 15224 USA. [Keren, Ron] Childrens Hosp Philadelphia, Ctr Pediat Clin Effectiveness, Div Gen Pediat, Philadelphia, PA 19104 USA. [Ivanova, Anastasia] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Ziessman, Harvey A.] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA. [Cui, Gang] Univ N Carolina, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA. [Mattoo, Tej K.] Wayne State Univ, Sch Med, Childrens Hosp Michigan, Div Nephrol & Hypertens, Detroit, MI USA. [Nadkarni, Milan D.] Wake Forest Sch Med, Brenner Childrens Hosp, Pediat Emergency Dept, Winston Salem, NC USA. [Moxey-Mims, Marva] NIDDK, NIH, Bethesda, MD 20892 USA. [Primack, William A.] Univ N Carolina, Kidney Ctr, Chapel Hill, NC USA. RP Shaikh, N (reprint author), Univ Pittsburgh, Sch Med, Childrens Hosp Pittsburgh UPMC, Div Gen Acad Pediat, One Childrens Hosp Dr,4401 Penn Ave, Pittsburgh, PA 15224 USA. EM nader.shaikh@chp.edu FU NIDDK NIH HHS [U01 DK074059] NR 15 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 EI 1432-1998 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD OCT PY 2016 VL 46 IS 11 BP 1573 EP 1578 DI 10.1007/s00247-016-3649-0 PG 6 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA DY5WX UT WOS:000385176200011 PM 27287454 ER PT J AU Lopez, G Bayulkem, K Hallett, M AF Lopez, G. Bayulkem, K. Hallett, M. TI Progressive supranuclear palsy (PSP): Richardson syndrome and other PSP variants SO ACTA NEUROLOGICA SCANDINAVICA LA English DT Review DE atypical parkinsonism; phenomenology; progressive supranuclear palsy; Richardson syndrome; tauopathy ID PRIMARY LATERAL SCLEROSIS; CORTICOBASAL DEGENERATION; FRONTOTEMPORAL DEMENTIA; ESSENTIAL TREMOR; NONFLUENT APHASIA; PARKINSONISM; DIAGNOSIS; CRITERIA; APRAXIA; SPEECH AB Phenotypic heterogeneity of progressive supranuclear palsy (PSP) has been increasingly reported in the literature and can be the source of incorrect clinical diagnosis particularly in the early stages of the disease when the classically associated symptoms of early falls and supranuclear gaze palsy may not be apparent. In addition to Richardson syndrome (RS), several atypical clinical phenotypes have been described. Advances in genetic, neuroimaging, and biochemical/molecular technologies contribute to the identification of these clinical subtypes in the context of typical PSP pathological findings. Our goal is to review the phenomenology reported in the literature that is associated with confirmed histopathological changes consistent with a PSP diagnosis and to highlight the clinical spectrum of PSP. A systematic review of the literature in PubMed through July 2015 using MeSH terms and key words related to PSP was conducted. Articles describing PSP classifications, diagnostic criteria, and case reports were reviewed and summarized. Additional PSP phenotypes not seen in recent clinicopathological studies are included. These include primary lateral sclerosis, pallido-nigro-luysian degeneration, axonal dystrophy, and multiple system atrophy in the spectrum of atypical PSP variants beyond the traditionally classified PSP subtypes. This review is intended to help with the diagnostic challenges of atypical PSP variants. We believe that large multicenter clinicopathological studies will help expand our understanding of etiology and specific mechanisms of neurodegeneration and will aid in the appropriate interpretation of outcomes when conducting clinical and basic science research. C1 [Lopez, G.] NHGRI, Sect Mol Neurogenet, Med Genet Branch, Intramural Res Program,NIH, Bethesda, MD 20892 USA. [Bayulkem, K.; Hallett, M.] NINDS, Human Motor Control Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. RP Lopez, G (reprint author), NHGRI, Sect Mol Neurogenet, Med Genet Branch, Intramural Res Program,NIH, Bethesda, MD 20892 USA. EM glopez@mail.nih.gov NR 45 TC 0 Z9 0 U1 5 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-6314 EI 1600-0404 J9 ACTA NEUROL SCAND JI Acta Neurol. Scand. PD OCT PY 2016 VL 134 IS 4 BP 242 EP 249 DI 10.1111/ane.12546 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA DW4OI UT WOS:000383622300001 PM 27070344 ER PT J AU Doussau, A Grady, C AF Doussau, Adelaide Grady, Christine TI The Ethics of Studying Financial Incentives in Public Health Implementation: Study Design Challenges SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material ID CLUSTER RANDOMIZED-TRIAL C1 [Doussau, Adelaide; Grady, Christine] NIH, 10 Ctr Dr,Bldg 10, Bethesda, MD 20892 USA. RP Doussau, A (reprint author), NIH, Dept Bioeth, Ctr Clin, Bioeth, 10 Ctr Dr,Bldg 10, Bethesda, MD 20892 USA. EM adelaide.doussau@gmail.com NR 10 TC 0 Z9 0 U1 1 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1526-5161 EI 1536-0075 J9 AM J BIOETHICS JI Am. J. Bioeth. PD OCT PY 2016 VL 16 IS 10 BP 78 EP 80 DI 10.1080/15265161.2016.1214322 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA DX6ZU UT WOS:000384536000031 PM 27653414 ER PT J AU Rosenkrantz, AB Oto, A Turkbey, B Westphalen, AC AF Rosenkrantz, Andrew B. Oto, Aytekin Turkbey, Baris Westphalen, Antonio C. TI Reply to "Standardizing Biparametric MRI to Simplify and Improve Prostate Imaging Reporting and Data System, Version 2, in Prostate Cancer Management" SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter ID PI-RADS; BIOPSY C1 [Rosenkrantz, Andrew B.] NYU, Langone Med Ctr, Sch Med, New York, NY 10012 USA. [Oto, Aytekin] Univ Chicago, Chicago, IL 60637 USA. [Turkbey, Baris] NCI, NIH, Bethesda, MD 20892 USA. [Westphalen, Antonio C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Rosenkrantz, AB (reprint author), NYU, Langone Med Ctr, Sch Med, New York, NY 10012 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 2016 VL 207 IS 4 BP W76 EP W76 DI 10.2214/AJR.16.16563 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DX7LF UT WOS:000384568100008 ER PT J AU Costa, VD Kakalios, LC Averbeck, BB AF Costa, Vincent D. Kakalios, Laura C. Averbeck, Bruno B. TI Blocking Serotonin but Not Dopamine Reuptake Alters Neural Processing During Perceptual Decision Making SO BEHAVIORAL NEUROSCIENCE LA English DT Article DE serotonin; dopamine; impulsivity; perceptual inference; drift diffusion model ID CENTRAL 5-HT DEPLETION; PARKINSONS-DISEASE; DELAYED REWARDS; REACTION-TIME; IMPULSIVITY; NEURONS; PERFORMANCE; ACTIVATION; BEHAVIOR; RATS AB Dopamine and serotonin have opponent interactions on aspects of impulsivity. Therefore we wanted to test the hypothesis that dopamine and serotonin would have opposing effects on speed-accuracy trade offs in a perceptual decision making task. Unlike other behavioral measures of impulsivity, perceptual decision making allows us to determine whether decreasing premature responses, often interpreted as decreased impulsivity, corresponds to increased behavioral performance. We administered GBR-12909 (a dopamine transporter blocker), escitalopram (a serotonin transporter blocker), or saline in separate sessions to 3 rhesus macaques. We found that animals had slower reaction times (RTs) on escitalopram than on GBR-12909 or saline. However, they were also least accurate on escitalopram. Animals were faster, although nonsignificantly, on GBR than saline and had equivalent accuracy. Administration of GBR-12909 did cause animals to be faster in error trials than correct trials. Therefore, from the point of view of RTs the animals were less impulsive on escitalopram. However, the decreased accuracy of the monkeys shows that they were not able to make use of their slower response times to make more accurate decisions. Therefore, impulsivity was reduced on escitalopram, but at the expense of a slower information-processing rate in the perceptual inference task. C1 [Costa, Vincent D.; Kakalios, Laura C.; Averbeck, Bruno B.] NIMH, Neuropsychol Lab, NIH, Bldg 49,Room 1B80,49 Convent Dr,MSC 4415, Bethesda, MD 20892 USA. RP Averbeck, BB (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 49,Room 1B80,49 Convent Dr,MSC 4415, Bethesda, MD 20892 USA. EM bruno.averbeck@nih.gov OI Costa, Vincent/0000-0002-5412-8945 FU Intramural Research Program of the National Institute of Mental Health FX This work was supported by the Intramural Research Program of the National Institute of Mental Health. NR 37 TC 0 Z9 0 U1 4 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 EI 1939-0084 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD OCT PY 2016 VL 130 IS 5 BP 461 EP 468 DI 10.1037/bne0000162 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA DX6XR UT WOS:000384529900001 PM 27513807 ER PT J AU Castillo, JJ Garcia-Sanz, R Hatjiharissi, E Kyle, RA Leleu, X McMaster, M Merlini, G Minnema, MC Morra, E Owen, RG Poulain, S Stone, MJ Tam, C Varettoni, M Dimopoulos, MA Treon, SP Kastritis, E AF Castillo, Jorge J. Garcia-Sanz, Ramon Hatjiharissi, Evdoxia Kyle, Robert A. Leleu, Xavier McMaster, Mary Merlini, Giampaolo Minnema, Monique C. Morra, Enrica Owen, Roger G. Poulain, Stephanie Stone, Marvin J. Tam, Constantine Varettoni, Marzia Dimopoulos, Meletios A. Treon, Steven P. Kastritis, Efstathios TI Recommendations for the diagnosis and initial evaluation of patients with Waldenstrom Macroglobulinaemia: A Task Force from the 8th International Workshop on Waldenstrom Macroglobulinaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE Waldenstrom macroglobulinaemia; anaemia; neuropathy; hyperviscosity; Bing-Neel syndrome; amyloidosis ID CONSENSUS PANEL RECOMMENDATIONS; IGM MONOCLONAL GAMMOPATHY; END RESULTS DATABASE; BING-NEEL SYNDROME; MYD88 L265P; LYMPHOPLASMACYTIC LYMPHOMA; CXCR4 MUTATIONS; HYPERVISCOSITY SYNDROME; GENOMIC LANDSCAPE; LIGHT-CHAIN AB The diagnosis of Waldenstrom macroglobulinaemia (WM) can be challenging given the variety of signs and symptoms patients can present. Furthermore, once the diagnosis of WM is established, the initial evaluation should be thorough as well as appropriately directed. During the 8th International Workshop for WM in London, United Kingdom, a multi-institutional task force was formed to develop consensus recommendations for the diagnosis and initial evaluation of patients with WM. In this document, we present the results of the deliberations that took place to address these issues. We provide recommendations for history-taking and physical examination, laboratory studies, bone marrow aspiration and biopsy analysis and imaging studies. We also provide guidance on the initial evaluation of special situations, such as anaemia, hyperviscosity, neuropathy, Bing-Neel syndrome and amyloidosis. We hope these recommendations serve as a practical guidance to clinicians taking care of patients with a suspected or an established diagnosis of WM. C1 [Castillo, Jorge J.; Treon, Steven P.] Harvard Med Sch, Dana Farber Canc Inst, Bing Ctr Waldenstrom Macroglobulinemia, 450 Brookline Ave,M221, Boston, MA 02215 USA. [Garcia-Sanz, Ramon] Hosp Univ Salamanca, Salamanca, Spain. [Hatjiharissi, Evdoxia] Theagene Hosp Thessaloniki, Dept Haematol, Thessaloniki, Greece. [Kyle, Robert A.] Mayo Clin, Div Hematol, Rochester, MN USA. [Leleu, Xavier] CHU Poitiers, La Mil Hosp, Poitiers, France. [McMaster, Mary] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Merlini, Giampaolo] Univ Pavia, Fdn IRCCS Policlin San Matteo, Amyloidosis Res & Treatment Ctr, Pavia, Italy. [Minnema, Monique C.] UMC Utrecht Canc Ctr, Dept Haematol, Utrecht, Netherlands. [Morra, Enrica] Osped Niguarda Ca Granda, Div Haematol, Milan, Italy. [Owen, Roger G.] Leeds Teaching Hosp NHS Trust, St Jamess Inst Oncol, Leeds, W Yorkshire, England. [Poulain, Stephanie] Ctr Hosp Valenciennes, Serv Hematol Immunol Cytogenet, Valenciennes, France. [Stone, Marvin J.] Baylor Charles Sammons Canc Ctr, Dept Oncol, Dallas, TX USA. [Tam, Constantine] Univ Melbourne, Dept Haematol, Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Varettoni, Marzia] Univ Pavia, Fdn IRCCS Policlin San Matteo, Dept Haematol Oncol, Pavia, Italy. [Dimopoulos, Meletios A.; Kastritis, Efstathios] Univ Athens, Dept Clin Therapeut, Sch Med, Athens, Greece. RP Castillo, JJ (reprint author), Harvard Med Sch, Dana Farber Canc Inst, Bing Ctr Waldenstrom Macroglobulinemia, 450 Brookline Ave,M221, Boston, MA 02215 USA. EM jorgej_castillo@dfci.harvard.edu RI Garcia-Sanz, Ramon/B-7986-2017; OI Garcia-Sanz, Ramon/0000-0003-4120-2787; Castillo, Jorge/0000-0001-9490-7532 FU Abbvie; Gilead; Millennium; Pharmacyclics; Celgene; Janssen; Roche; Onyx FX JJC received honoraria from Celgene and Pharmacyclics, and research funding from Abbvie, Gilead, Millennium and Pharmacyclics. RGS received honoraria from Bristol-Myers Squibb, Janssen and Takeda and. EH received honoraria from Amgen, Gilead and Janssen. GM received honoraria from GlaxoSmithKline, Janssen and Millennium-Takeda. RGO received honoraria from Celgene, Janssen, Pharmacyclics and Roche, and research funding from Celgene. CT received honoraria and research funding from Janssen and Roche. MAD received honoraria from Amgen, Celgene, Janssen and Novartis. SPT received research funding and/or honoraria from Gilead, Janssen, Onyx and Pharmacyclics. EK received honoraria from Amgen, Janssen and Takeda and. RAK, XL, MM, MCM, EM, SP, MJS, MV have no conflict of interest to disclose. NR 58 TC 2 Z9 2 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2016 VL 175 IS 1 BP 77 EP 86 DI 10.1111/bjh.14196 PG 10 WC Hematology SC Hematology GA DY0TE UT WOS:000384808300011 PM 27378193 ER PT J AU Schinasi, LH Brown, EE Camp, NJ Wang, SS Hofmann, JN Chiu, BC Miligi, L Freeman, LEB de Sanjose, S Bernstein, L Monnereau, A Clavel, J Tricot, GJ Atanackovic, D Cocco, P Orsi, L Dosman, JA McLaughlin, JR Purdue, MP Cozen, W Spinelli, JJ de Roos, AJ AF Schinasi, Leah H. Brown, Elizabeth E. Camp, Nicola J. Wang, Sophia S. Hofmann, Jonathan N. Chiu, Brian C. Miligi, Lucia Freeman, Laura E. Beane de Sanjose, Silvia Bernstein, Leslie Monnereau, Alain Clavel, Jacqueline Tricot, Guido J. Atanackovic, Djordje Cocco, Pierluigi Orsi, Laurent Dosman, James A. McLaughlin, John R. Purdue, Mark P. Cozen, Wendy Spinelli, John J. de Roos, Anneclaire J. TI Multiple myeloma and family history of lymphohaematopoietic cancers: Results from the International Multiple Myeloma Consortium SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE multiple myeloma; epidemiology; lympho-haematopoietic malignancies; family history; lymphoma ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MONOCLONAL GAMMOPATHY; UNDETERMINED SIGNIFICANCE; HEMATOLOGIC MALIGNANCIES; 1ST-DEGREE RELATIVES; LYMPHOID NEOPLASMS; RISK; OCCUPATION; VARIANTS; EXPOSURE AB Family clusters of multiple myeloma (MM) suggest disease heritability. Nevertheless, patterns of inheritance and the importance of genetic versus environmental risk factors in MM aetiology remain unclear. We pooled data from eleven case-control studies from the International Multiple Myeloma Consortium to characterize the association of MM risk with having a first-degree relative with a history of a lympho-haematapoietic cancer. Unconditional logistic regression models, adjusted for study, sex, age and education level, were used to estimate associations between MM risk and having a first-degree relative with a history of non-Hodgkin lymphoma, Hodgkin lymphoma, leukaemia or MM. Sex, African American race/ethnicity and age were explored as effect modifiers. A total of 2843 cases and 11470 controls were included. MM risk was elevated in association with having a first-degree relative with any lympho-haematapoietic cancer (Odds Ratio (OR)=129, 95% Confidence Interval (CI): 108-155). The association was particularly strong for having a first-degree relative with MM (OR=190, 95% CI: 126-287), especially among men (OR=413, 95% CI: 217-785) and African Americans (OR=552, 95% CI: 187-1627).These results support the hypothesis that genetic inheritance plays a role in MM aetiology. Future studies are warranted to characterize interactions of genetic markers with environmental exposures. C1 [Schinasi, Leah H.; de Roos, Anneclaire J.] Drexel Univ, Dornsife Sch Publ Hlth, Dept Environm & Occupat Hlth, Philadelphia, PA 19104 USA. [Brown, Elizabeth E.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Pathol, Birmingham, AL 35294 USA. [Brown, Elizabeth E.] Univ Alabama Birmingham, Sch Publ Hlth, Ctr Comprehens Canc, Sch Med, Birmingham, AL 35294 USA. [Camp, Nicola J.; Atanackovic, Djordje] Univ Utah, Sch Med, Div Hematol & Hematol Malignancies, Salt Lake City, UT USA. [Wang, Sophia S.; Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA USA. [Hofmann, Jonathan N.; Freeman, Laura E. Beane; Purdue, Mark P.] NCI, Occupat & Environm Epidemiol Branch, Div Canc & Genet, Rockville, MD USA. [Chiu, Brian C.] Univ Chicago, Dept Publ Hlth Sci, Chicago, IL 60637 USA. [Miligi, Lucia] Inst Study & Prevent Canc, Unit Environm & Occupat Hlth, Florence, Italy. [de Sanjose, Silvia] Catalan Inst Oncol, Canc Epidemiol Res Programme, Barcelona, Spain. [Monnereau, Alain; Clavel, Jacqueline; Orsi, Laurent] INSERM, U1153, Epidemiol & Biostat Sorbonne Paris Cite Ctr CRESS, Epidemiol Childhood & Adolescent Canc Team EPICEA, Villejuif, France. [Monnereau, Alain; Clavel, Jacqueline; Orsi, Laurent] Paris Descartes Univ, UMRS 1153, Epidemiol & Biostat Sorbonne Paris Cite Ctr CRESS, Paris, France. [Tricot, Guido J.] Univ Iowa, Internal Med, Iowa City, IA USA. [Cocco, Pierluigi] Univ Cagliari, Dept Publ Hlth Clin & Mol Med, Occupat Hlth Sect, Cagliari, Italy. [Dosman, James A.] Univ Saskatchewan, Canadian Ctr Hlth & Safety Agr, Saskatoon, SK, Canada. [McLaughlin, John R.] Publ Hlth Ontario, Toronto, ON, Canada. [Cozen, Wendy] Univ Southern Calif, USC Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. [Cozen, Wendy] Univ Southern Calif, USC Keck Sch Med, Dept Pathol, Los Angeles, CA USA. [Spinelli, John J.] Univ British Columbia, Sch Populat & Publ Hlth, Canc Control Res, BC Canc Agcy, Vancouver, BC, Canada. RP Schinasi, LH (reprint author), Drexel Univ, Sch Publ Hlth, Dept Environm & Occupat Hlth, Nesbitt Hall,3215 Market St, Philadelphia, PA 19104 USA. EM lhs36@drexel.edu RI Clavel, Jacqueline/Q-2750-2016; Beane Freeman, Laura/C-4468-2015 OI Clavel, Jacqueline/0000-0002-3616-7676; Beane Freeman, Laura/0000-0003-1294-4124 FU National Institute of Environmental Health Sciences [R21 ES021592]; Intramural Research Program of the NIH; Association pour la Recherche contre le Cancer; Fondation de France; AFSSET; NCI [U54CA118948, R21CA155951, R25CA76023, R01CA186646]; NCI (University of Alabama at Birmingham Comprehensive Cancer Center Support grant) [P30CA13148]; American Cancer Society [IRG60-001-47] FX This study was supported by the National Institute of Environmental Health Sciences grant R21 ES021592 (A.J.D.). The Connecticut Study and the Population Health Study were supported in part by the Intramural Research Program of the NIH. The ENGELA study (JC) was supported by grants from the Association pour la Recherche contre le Cancer, the Fondation de France, AFSSET and a donation from Faberge employees. The work conducted by E.E. Brown was supported, in part, by grants from the NCI (U54CA118948, R21CA155951, R25CA76023, R01CA186646, and the University of Alabama at Birmingham Comprehensive Cancer Center Support grant P30CA13148) and the American Cancer Society (IRG60-001-47). NR 47 TC 0 Z9 0 U1 5 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2016 VL 175 IS 1 BP 87 EP 101 DI 10.1111/bjh.14199 PG 15 WC Hematology SC Hematology GA DY0TE UT WOS:000384808300012 PM 27330041 ER PT J AU Lewis, MD Francisco, AF Taylor, MC Jayawardhana, S Kelly, JM AF Lewis, Michael D. Francisco, Amanda Fortes Taylor, Martin C. Jayawardhana, Shiromani Kelly, John M. TI Host and parasite genetics shape a link between Trypanosoma cruzi infection dynamics and chronic cardiomyopathy SO CELLULAR MICROBIOLOGY LA English DT Article ID CHRONIC-CHAGAS-CARDIOMYOPATHY; HEART-DISEASE; IMMUNE-SYSTEM; LOOKING-BACK; INBRED MICE; AUTOIMMUNITY; PATHOGENESIS; MYOCARDITIS; LESIONS; CLONES AB Host and parasite diversity are suspected to be key factors in Chagas disease pathogenesis. Experimental investigation of underlying mechanisms is hampered by a lack of tools to detect scarce, pleiotropic infection foci. We developed sensitive imaging models to track Trypanosoma cruzi infection dynamics and quantify tissue-specific parasite loads, with minimal sampling bias. We used this technology to investigate cardiomyopathy caused by highly divergent parasite strains in BALB/c, C3H/HeN and C57BL/6 mice. The gastrointestinal tract was unexpectedly found to be the primary site of chronic infection in all models. Immunosuppression induced expansion of parasite loads in the gut and was followed by widespread dissemination. These data indicate that differential immune control of T. cruzi occurs between tissues and shows that the large intestine and stomach provide permissive niches for active infection. The end-point frequency of heart-specific infections ranged from 0% in TcVI-CLBR-infected C57BL/6 to 88% in TcI-JR-infected C3H/HeN mice. Nevertheless, infection led to fibrotic cardiac pathology in all models. Heart disease severity was associated with the model-dependent frequency of dissemination outside the gut and inferred cumulative heart-specific parasite loads. We propose a model of cardiac pathogenesis driven by periodic trafficking of parasites into the heart, occurring at a frequency determined by host and parasite genetics. C1 [Lewis, Michael D.; Francisco, Amanda Fortes; Taylor, Martin C.; Jayawardhana, Shiromani; Kelly, John M.] London Sch Hyg & Trop Med, Dept Pathogen Mol Biol, Keppel St, London WC1E 7HT, England. [Lewis, Michael D.] NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Lewis, MD (reprint author), London Sch Hyg & Trop Med, Dept Pathogen Mol Biol, Keppel St, London WC1E 7HT, England.; Lewis, MD (reprint author), NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. EM michael.lewis@lshtm.ac.uk FU Wellcome Trust [084175]; British Heart Foundation [PG/13/88/30556]; Bill and Melinda Gates Foundation [OPPGH5337]; Drugs for Neglected Diseases initiative (DNDi); EU Marie Curie Fellowship; NIAID, NIH FX This work was supported by Wellcome Trust Grant 084175, British Heart Foundation Grant PG/13/88/30556, Bill and Melinda Gates Foundation Grant OPPGH5337 and the Drugs for Neglected Diseases initiative (DNDi). MDL is currently supported by an EU Marie Curie Fellowship and the intramural research programme of the NIAID, NIH. The authors thank LSHTM Biological Services Facility staff for technical support, Bruce Branchini for the PpyRE9h luciferase gene, Hernan Carrasco for the JR parasite stock, Laura Muller and Monica Campos for experimental assistance, Cheryl Whitehorn and Louisa Messenger for triatomine samples and Michael Miles for valuable support, discussions and advice. NR 61 TC 3 Z9 3 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-5814 EI 1462-5822 J9 CELL MICROBIOL JI Cell Microbiol. PD OCT PY 2016 VL 18 IS 10 BP 1429 EP 1443 DI 10.1111/cmi.12584 PG 15 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA DW4KS UT WOS:000383612400009 PM 26918803 ER PT J AU Roudnitzky, N Risso, D Drayna, D Behrens, M Meyerhof, W Wooding, SP AF Roudnitzky, Natacha Risso, Davide Drayna, Dennis Behrens, Maik Meyerhof, Wolfgang Wooding, Stephen P. TI Copy Number Variation in TAS2R Bitter Taste Receptor Genes: Structure, Origin, and Population Genetics SO CHEMICAL SENSES LA English DT Article DE bitter; evolution; genetic; genomic; natural selection; taste receptor ID CELL-LINE PANEL; HUMAN GENOME; DEVELOPMENTAL DELAY; POSITIVE SELECTION; ALLELIC VARIATION; EVOLUTION; SENSITIVITY; HUMANS; DIVERSITY; VARIABILITY AB Bitter taste receptor genes (TAS2Rs) harbor extensive diversity, which is broadly distributed across human populations and strongly associated with taste response phenotypes. The majority of TAS2R variation is composed of single-nucleotide polymorphisms. However, 2 closely positioned loci at 12p13, TAS2R43 and -45, harbor high-frequency deletion (Delta) alleles in which genomic segments are absent, resulting in copy number variation (CNV). To resolve their chromosomal structure and organization, we generated maps using long-range contig alignments and local sequencing across the TAS2R43-45 region. These revealed that the deletion alleles (43 Delta and 45 Delta) are 37.8 and 32.2 kb in length, respectively and span the complete coding region of each gene (similar to 1 kb) along with extensive up-and downstream flanking sequence, producing separate CNVs at the 2 loci. Comparisons with a chimpanzee genome, which contained intact homologs of TAS2R43, -45, and nearby TAS2Rs, indicated that the deletions evolved recently, through unequal recombination in a cluster of closely related loci. Population genetic analyses in 946 subjects from 52 worldwide populations revealed that copy number ranged from 0 to 2 at both TAS2R43 and TAS2R45, with 43 Delta and 45 Delta occurring at high global frequencies (0.33 and 0.18). Estimated recombination rates between the loci were low (rho = 2.7 x 10(-4); r = 6.6 x 10(-9)) and linkage disequilibrium was high (D' = 1.0), consistent with their adjacent genomic positioning and recent origin. Geographic variation pointed to an African origin for the deletions. However, no signatures of natural selection were found in population structure or integrated haplotype scores spanning the region, suggesting that patterns of diversity at TAS2R43 and -45 are primarily due to genetic drift. C1 [Roudnitzky, Natacha; Behrens, Maik; Meyerhof, Wolfgang] German Inst Human Nutr Potsdam Rehbrucke, Dept Mol Genet, Arthur Scheunert Allee 114-116, D-14558 Nuthetal, Germany. [Risso, Davide; Drayna, Dennis] NIDCD, NIH, Bethesda, MD 20892 USA. [Wooding, Stephen P.] Univ Calif Merced, Hlth Sci Res Inst, 5200 North Lake Rd, Merced, CA 95343 USA. RP Wooding, SP (reprint author), Univ Calif Merced, Hlth Sci Res Inst, 5200 North Lake Rd, Merced, CA 95343 USA. EM swooding@ucmerced.edu NR 64 TC 0 Z9 0 U1 18 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0379-864X EI 1464-3553 J9 CHEM SENSES JI Chem. Senses PD OCT PY 2016 VL 41 IS 8 BP 3 EP 13 DI 10.1093/chemse/bjw067 PG 11 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA DX5FZ UT WOS:000384406500001 PM 27340135 ER PT J AU Papadakis, GZ Millo, C Sadowski, SM Bagci, U Patronas, NJ AF Papadakis, Georgios Z. Millo, Corina Sadowski, Samira M. Bagci, Ulas Patronas, Nicholas J. TI Epididymal Cystadenomas in von Hippel-Lindau Disease Showing Increased Activity on Ga-68 DOTATATE PET/CT SO CLINICAL NUCLEAR MEDICINE LA English DT Editorial Material DE von Hippel-Lindau (VHL) disease; Ga-68 DOTATATE PET/CT; epididymal; cystadenomas; somatostatin receptors imaging ID CEREBELLAR HEMANGIOBLASTOMA; IMAGING FEATURES AB von Hippel-Lindau (VHL) disease is a familial cancer syndrome characterized by the development of a variety of malignant and benign tumors, including epididymal cystadenomas. We report a case of a VHL patient with bilateral epididymal cystadenomas who was evaluated with Ga-68 DOTATATE PET/CT, showing intensely increased activity (SUVmax, 21.6) associated with the epididymal cystadenomas, indicating cell-surface overexpression of somatostatin receptors. The presented case supports the usefulness of somatostatin receptor imaging using Ga-68 DOTA-conjugated peptides for detection and follow-up of VHL manifestations, as well as surveillance of asymptomatic gene carriers. C1 [Papadakis, Georgios Z.; Patronas, Nicholas J.] NCI, Radiol & Imaging Sci, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. [Millo, Corina] NCI, Div Nucl Med, RADIS, Ctr Clin,NIH, Bethesda, MD 20892 USA. [Sadowski, Samira M.] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA. [Sadowski, Samira M.] Univ Hosp Geneva, Endocrine & Thorac Surg, Geneva, Switzerland. [Bagci, Ulas] Univ Cent Florida, Dept Elect & Comp Sci, Ctr Comp Vis Res, Orlando, FL 32816 USA. RP Patronas, NJ (reprint author), NIH, Radiol & Imaging Sci, Warren Grant Magnuson Clin Ctr, Bldg 10,Room 1C361X 10,Ctr Dr, Bethesda, MD 20814 USA. EM NPatronas@cc.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 10 TC 2 Z9 2 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0363-9762 EI 1536-0229 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD OCT PY 2016 VL 41 IS 10 BP 781 EP 782 DI 10.1097/RLU.0000000000001314 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DX5WD UT WOS:000384452500023 PM 27454594 ER PT J AU Papadakis, GZ Millo, C Sadowski, SM Bagci, U Patronas, NJ AF Papadakis, Georgios Z. Millo, Corina Sadowski, Samira M. Bagci, Ulas Patronas, Nicholas J. TI Endolymphatic Sac Tumor Showing Increased Activity on Ga-68 DOTATATE PET/CT SO CLINICAL NUCLEAR MEDICINE LA English DT Editorial Material DE endolymphatic sac tumors; von Hippel-Lindau disease; Ga-68-DOTATATE PET/CT; somatostatin receptors-imaging ID HIPPEL-LINDAU-DISEASE AB Endolymphatic sac tumors (ELSTs) are rare tumors arising from the epithelium of the endolymphatic sac and duct that can be either sporadic or associated with von Hippel-Lindau (VHL) disease. We report a case of a VHL patient with histologically proven residual ELST who underwent Ga-68 DOTATATE PET/CT showing increased activity (SUVmax, 6.29) by the ELST. The presented case of a VHL-associated ELST with increased Ga-68 DOTATATE uptake indicates cell-surface expression of somatostatin receptors by this tumor, suggesting the potential application of somatostatin receptor imaging using Ga-68 DOTA-conjugated peptides in the workup and management of these patients. C1 [Papadakis, Georgios Z.; Patronas, Nicholas J.] NCI, Radiol & Imaging Sci, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. [Millo, Corina] NCI, Div Nucl Med, RAD&IS, Ctr Clin,NIH, Bethesda, MD 20892 USA. [Sadowski, Samira M.] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA. [Sadowski, Samira M.] Univ Hosp Geneva, Endocrine & Thorac Surg, Geneva, Switzerland. [Bagci, Ulas] Univ Cent Florida, Dept Elect & Comp Sci, Ctr Comp Vis Res, Orlando, FL 32816 USA. RP Patronas, NJ (reprint author), NIH, Neuroradiol Sect, Warren Grant Magnuson Clin Ctr, Bldg 10,Room 1C361X 10,Ctr Dr, Bethesda, MD 20814 USA. EM NPatronas@cc.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 12 TC 2 Z9 2 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0363-9762 EI 1536-0229 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD OCT PY 2016 VL 41 IS 10 BP 783 EP 784 DI 10.1097/RLU.0000000000001315 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DX5WD UT WOS:000384452500024 PM 27454593 ER PT J AU Knickelbein, JE Abbott, AB Chew, EY AF Knickelbein, Jared E. Abbott, Akshar B. Chew, Emily Y. TI Fenofibrate and Diabetic Retinopathy SO CURRENT DIABETES REPORTS LA English DT Review DE Diabetic retinopathy; Diabetic macular edema; Fenofibrate ID CONTROL-CARDIOVASCULAR-RISK; RANDOMIZED CONTROLLED-TRIAL; MACULAR EDEMA; MELLITUS; PREVALENCE; COMPLICATIONS; RANIBIZUMAB; PROGRESSION; DYSLIPIDEMIA; ASSOCIATION AB Diabetic retinopathy, a common and sight-threatening microvascular complication of diabetes mellitus, is a leading cause of blindness among working-aged adults. Medical therapies including intensive control of hyperglycemia and hypertension have been shown to reduce the incidence and progression of diabetic retinopathy. The association of dyslipidemia and treatment with statins with diabetic retinopathy is inconsistent in epidemiologic studies. However, two recent randomized clinical trials have demonstrated beneficial effects of systemic fenofibrate therapy in reducing the progression of diabetic retinopathy independently of serum lipid levels. These findings suggest that fenofibrate may be an effective strategy for reducing the progression of diabetic retinopathy, thus reducing the large and growing public health burden of treating the sight-threatening complications of diabetic retinopathy. C1 [Knickelbein, Jared E.; Abbott, Akshar B.; Chew, Emily Y.] NEI, NIH, 10 Ctr Dr,10-10D45, Bethesda, MD 20892 USA. [Chew, Emily Y.] NEI, Div Epidemiol & Clin Applicat, Clin Trials Branch, NIH, Bldg 10 Clin Res Ctr,Room3-2531,10 Ctr Dr, Bethesda, MD 20892 USA. RP Chew, EY (reprint author), NEI, NIH, 10 Ctr Dr,10-10D45, Bethesda, MD 20892 USA.; Chew, EY (reprint author), NEI, Div Epidemiol & Clin Applicat, Clin Trials Branch, NIH, Bldg 10 Clin Res Ctr,Room3-2531,10 Ctr Dr, Bethesda, MD 20892 USA. EM Knickelbeinje@nei.nih.gov; akshar.abbott@nih.gov; echew@nei.nih.gov FU Intramural Research Program of the NIH, NEI FX This research was supported by the Intramural Research Program of the NIH, NEI. NR 45 TC 1 Z9 1 U1 2 U2 2 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 EI 1539-0829 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD OCT PY 2016 VL 16 IS 10 AR 90 DI 10.1007/s11892-016-0786-7 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DX7CG UT WOS:000384543100002 PM 27525681 ER PT J AU Robinson, C Collins, MT Boyce, AM AF Robinson, Cemre Collins, Michael T. Boyce, Alison M. TI Fibrous Dysplasia/McCune-Albright Syndrome: Clinical and Translational Perspectives SO CURRENT OSTEOPOROSIS REPORTS LA English DT Review DE Fibrous dysplasia; McCune-Albright syndrome; GNAS gene; G(s)alpha; FGF23 ID MARROW STROMAL CELLS; DENOSUMAB TREATMENT; ACTIVATING MUTATIONS; INTRAVENOUS PAMIDRONATE; MONOZYGOTIC TWINS; SKELETAL LESIONS; RANK-LIGAND; STEM-CELLS; G-PROTEIN; BONE AB Fibrous dysplasia (FD) is an uncommon and debilitating skeletal disorder resulting in fractures, deformity, functional impairment, and pain. It arises from post-zygotic somatic activating mutations in GNAS, in the cAMP-regulating transcript alpha-subunit, G(s)alpha. Constitutive G(s) signaling results in activation of adenylyl cyclase and dysregulated cAMP production. In the skeleton, this leads to the development of FD lesions with abnormal bone matrix, trabeculae, and collagen, produced by undifferentiated mesenchymal cells. FD may occur in isolation or in combination with extraskeletal manifestations, including hyperfunctioning endocrinopathies and cafc-au-lait macules, termed McCune-Albright syndrome (MAS). This review summarizes current clinical and translational perspectives in FD/MAS, with an emphasis on FD pathogenesis, natural history, pre-clinical and clinical investigation, and future directions. C1 [Robinson, Cemre; Collins, Michael T.; Boyce, Alison M.] Natl Inst Dent & Craniofacial Res, Sect Skeletal Disorders andMineral Homeostasis, Craniofacial & Skeletal Dis Branch, NIH, 30 Convent Dr Room 228 MSC 4320, Bethesda, MD 20892 USA. [Boyce, Alison M.] Childrens Natl Hlth Syst, Div Endocrinol & Diabet, Washington, DC 20010 USA. [Boyce, Alison M.] Childrens Natl Hlth Syst, Div Orthopaed & Sports Med, Bone Hlth Program, Washington, DC 20010 USA. RP Boyce, AM (reprint author), Natl Inst Dent & Craniofacial Res, Sect Skeletal Disorders andMineral Homeostasis, Craniofacial & Skeletal Dis Branch, NIH, 30 Convent Dr Room 228 MSC 4320, Bethesda, MD 20892 USA.; Boyce, AM (reprint author), Childrens Natl Hlth Syst, Div Endocrinol & Diabet, Washington, DC 20010 USA.; Boyce, AM (reprint author), Childrens Natl Hlth Syst, Div Orthopaed & Sports Med, Bone Hlth Program, Washington, DC 20010 USA. EM boyceam@mail.nih.gov FU Intramural Research Program of the National Institute of Dental and Craniofacial Research FX This research was supported by the Intramural Research Program of the National Institute of Dental and Craniofacial Research NR 72 TC 1 Z9 1 U1 3 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1544-2241 J9 CURR OSTEOPOROS REP JI Curr. Osteoporos. Rep. PD OCT PY 2016 VL 14 IS 5 BP 178 EP 186 DI 10.1007/s11914-016-0317-0 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DX7DH UT WOS:000384546100003 PM 27492469 ER PT J AU Provinciali, N Suen, C Dunn, BK DeCensi, A AF Provinciali, Nicoletta Suen, Chen Dunn, Barbara K. DeCensi, Andrea TI Raloxifene hydrochloride for breast cancer risk reduction in postmenopausal women SO EXPERT REVIEW OF CLINICAL PHARMACOLOGY LA English DT Article DE Clinical trials; raloxifene; breast cancer risk; cancer prevention; pharmacology ID ESTROGEN-RECEPTOR MODULATOR; RANDOMIZED CONTROLLED-TRIAL; SURGICAL ADJUVANT BREAST; CORONARY-HEART-DISEASE; BONE-MINERAL DENSITY; STAR P-2 TRIAL; PREMENOPAUSAL WOMEN; HORMONE-THERAPY; CLINICAL-TRIAL; CARDIOVASCULAR EVENTS AB Introduction: Raloxifene is an estrogen receptor modulator which competes with estrogens for binding to the estrogen receptor. Based on the results of the STAR (Study of Tamoxifen And Raloxifene) trial, raloxifene has been approved by the U.S. Food and Drug Administration for the reduction of breast cancer (BC) risk in postmenopausal women at increased risk. Areas covered: This analysis reviews the activity of raloxifene and the clinical trials for non-BC indications which led to investigate its use as BC preventive agent. We review the trial establishing its efficacy for BC prevention and the meta-analyses including different SERMs for BC prevention. Expert commentary: Compared with tamoxifen, raloxifene has shown a slightly lower efficacy in reducing BC risk and a better safety profile. Raloxifene also offers to postmenopausal women a benefit in terms of osteoporosis. Future research should investigate its use in premenopausal women and in association with other preventive agents. C1 [Provinciali, Nicoletta; DeCensi, Andrea] EO Osped Galliera, Div Med Oncol, Mura Cappuccine 14, I-16128 Genoa, Italy. [Suen, Chen; Dunn, Barbara K.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [DeCensi, Andrea] European Inst Oncol, Div Canc Prevent & Genet, Milan, Italy. RP Provinciali, N (reprint author), EO Osped Galliera, Div Med Oncol, Mura Cappuccine 14, I-16128 Genoa, Italy. EM nicoletta.provinciali@galliera.it NR 67 TC 0 Z9 0 U1 5 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1751-2433 EI 1751-2441 J9 EXPERT REV CLIN PHAR JI Expert Rev. Clin. Pharmacol. PD OCT PY 2016 VL 9 IS 10 BP 1263 EP 1272 DI 10.1080/17512433.2016.1231575 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DX8MR UT WOS:000384643500002 ER PT J AU Lynch, JA Berse, B Petkov, V Filipski, K Zhou, YJ Khoury, MJ Hassett, M Freedman, AN AF Lynch, Julie A. Berse, Brygida Petkov, Valentina Filipski, Kelly Zhou, Yingjun Khoury, Muin J. Hassett, Michael Freedman, Andrew N. TI Implementation of the 21-gene recurrence score test in the United States in 2011 SO GENETICS IN MEDICINE LA English DT Article DE breast cancer; cancer genomics; dissemination; equity; implementation ID NEGATIVE BREAST-CANCER; GENE-EXPRESSION; ASSAY; POPULATION; ESTROGEN; SUBTYPES; RISK; CHEMOTHERAPY; PATTERNS; WOMEN AB Purpose: We examined hospital use of the 21-gene breast cancer test in the United States. We report state-level differences in utilization and propose a model for predicting implementation of -guideline-recommended genomic testing. Methods: Genomic Health provided test orders for calendar year 2011. We summarized utilization at the hospital and state levels. Using logistic regression, we analyzed the association between the likelihood to order the test and the hospital's institutional and regional characteristics. Results: In 2011, 45% of 4,712 acute-care hospitals ordered the test, which suggests that 25% of newly diagnosed invasive female breast cancer cases were tested. Significant predictors of testing included participation in National Cancer Institute (NCI) clinical research cooperative groups (odds ratio (OR) 3.73; 95% confidence interval, 2.96-4.70), advanced imaging (OR, 2.19; CI, 1.78-2.68), high-complexity laboratory (OR, 2.15; CI, 1.24-3.70), affiliation with a medical school (OR, 1.57; CI, 1.31-1.88), and reconstructive surgery (OR, 1.23; CI, 1.01-1.50). Significant regional predictors included metropolitan county (OR, 3.77; CI, 2.83-5.03), above-mean income (OR, 1.37; CI, 1.11-1.69), and education (OR, 1.26; CI, 1.03-1.54). Negative predictors included designation as a critical-access hospital (OR, 0.10; CI, 0.07-0.14) and distance from an NCI cancer center (OR, 0.998; CI, 0.997-0.999), with a 15% decrease in likelihood for every 100 miles. Conclusion: Despite considerable market penetration of the test, there are significant regional and site-of-care differences in implementation, particularly in rural states. C1 [Lynch, Julie A.] VA Salt Lake City Hlth Care Syst, Salt Lake City, UT 84148 USA. [Lynch, Julie A.; Berse, Brygida] RTI Int, Durham, NC 27709 USA. [Berse, Brygida] Boston Univ, Sch Med, Boston, MA 02118 USA. [Berse, Brygida] Vet Hlth Adm, Bedford, MA USA. [Petkov, Valentina; Filipski, Kelly; Zhou, Yingjun; Freedman, Andrew N.] NCI, NIH, Bethesda, MD 20892 USA. [Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA. [Khoury, Muin J.] NCI, Epidemiol & Genom Res Program, NIH, Bethesda, MD 20892 USA. [Hassett, Michael] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hassett, Michael] Harvard Med Sch, Boston, MA USA. RP Lynch, JA (reprint author), VA Salt Lake City Hlth Care Syst, Salt Lake City, UT 84148 USA.; Lynch, JA (reprint author), RTI Int, Durham, NC 27709 USA. EM Julie.Lynch@va.gov OI Lynch, Julie/0000-0003-0108-2127 FU National Cancer Institute FX This research was conducted while J.A.L. was a postdoctoral fellow within the Center for Healthcare Organization and Implementation Research (CHOIR), a Veterans Administration Health Services Research & Development Center of Excellence. She and B.B. are funded by the National Cancer Institute through an Interagency Agreement. Preliminary results were previously presented as a poster at the 49th American Society of Clinical Oncology Annual Meeting, 31 May 20. NR 34 TC 2 Z9 2 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD OCT PY 2016 VL 18 IS 10 BP 982 EP 990 DI 10.1038/gim.2015.218 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA DX8CN UT WOS:000384615800013 PM 26890451 ER PT J AU Kelly, NR Tanofsky-Kraff, M Vannucci, A Ranzenhofer, LM Altschul, AM Schvey, NA Shank, LM Brady, SM Galescu, O Kozlosky, M Yanovski, SZ Yanovski, JA AF Kelly, Nichole R. Tanofsky-Kraff, Marian Vannucci, Anna Ranzenhofer, Lisa M. Altschul, Annie M. Schvey, Natasha A. Shank, Lisa M. Brady, Sheila M. Galescu, Ovidiu Kozlosky, Merel Yanovski, Susan Z. Yanovski, Jack A. TI Emotion Dysregulation and Loss-of-Control Eating in Children and Adolescents SO HEALTH PSYCHOLOGY LA English DT Article DE emotion regulation; loss-of-control eating; binge eating; body mass; fat mass ID HANDLING MISSING DATA; BODY-MASS INDEX; SELF-REGULATION; ADULT OBESITY; OVERWEIGHT CHILDREN; BEHAVIOR CHECKLIST; PUBERTAL STAGE; MEDIATING ROLE; ENERGY-INTAKE; HIGH-RISK AB Objective: To examine the associations among self-reported loss-of-control (LOC) eating, emotion dysregulation, body mass, and objective energy intake among youth. Emotion dysregulation may be 1 individual factor that promotes excess energy intake and increases in body mass among youth with LOC eating. Method: Children and adolescents (N = 230; 8 to 17 years) enrolled in a nonintervention study completed a structured interview to determine the presence or absence of self-reported LOC eating. Children's emotion dysregulation was assessed via parent-report with the Child Behavior Checklist. Youth also completed 2 test meals to capture "binge" and "normal" eating. Body composition was examined using air displacement plethysmography. Results: After controlling for relevant covariates, youth with self-reported LOC eating had higher parent-reported emotion dysregulation than those without LOC. Parent-reported emotion dysregulation was also associated with greater observed energy intake (after accounting for body mass), as well as higher fat mass. Emotion dysregulation also moderated associations between LOC status/gender and body mass variables; among youth with self-reported LOC eating and girls, those with high parent-described emotion dysregulation (vs. low) had significantly higher fat mass and BMIz. Conclusions: Data from the current study suggest that emotion dysregulation may play a role in energy intake and obesity, particularly among youth with self-reported LOC eating and girls. Additional studies are needed to identify the prospective mechanisms linking poor emotion regulation and LOC eating. These mechanisms, in turn, may inform future interventions targeting excess energy intake and obesity in pediatric samples. C1 [Kelly, Nichole R.; Tanofsky-Kraff, Marian; Vannucci, Anna; Altschul, Annie M.; Schvey, Natasha A.; Shank, Lisa M.; Brady, Sheila M.; Galescu, Ovidiu; Kozlosky, Merel; Yanovski, Susan Z.; Yanovski, Jack A.] NIH, US Dept HHS, Bldg 10, Bethesda, MD 20892 USA. [Kelly, Nichole R.; Tanofsky-Kraff, Marian; Vannucci, Anna; Schvey, Natasha A.; Shank, Lisa M.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Ranzenhofer, Lisa M.] Brown Univ, Miriam Hosp, Alpert Med Sch, Providence, RI USA. RP Tanofsky-Kraff, M (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM marian.tanofsky-kraff@usuhs.edu OI Shank, Lisa/0000-0002-6922-7946 FU USUHS [R072IC]; Intramural Research Program, NIH from the NICHD [1ZIAHD000641]; NIMHD; Bench to Bedside Program; Office of Behavioral and Social Sciences Research (OBSSR) of the NIH; NIMH [5F31MH095348]; Division of Nutrition Research Coordination, NIH FX USUHS Grant R072IC (to Marian Tanofsky-Kraff). Intramural Research Program, NIH, Grant 1ZIAHD000641 from the NICHD with supplemental funding from NIMHD, the Bench to Bedside Program, the Office of Behavioral and Social Sciences Research (OBSSR) of the NIH (to Jack A. Yanovski), and NIMH 5F31MH095348 (to Lisa M. Ranzenhofer). Annie M. Altschul is supported by the Division of Nutrition Research Coordination, NIH. NR 59 TC 0 Z9 0 U1 7 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 EI 1930-7810 J9 HEALTH PSYCHOL JI Health Psychol. PD OCT PY 2016 VL 35 IS 10 BP 1110 EP 1119 DI 10.1037/hea0000389 PG 10 WC Psychology, Clinical; Psychology SC Psychology GA DX6XU UT WOS:000384530200007 PM 27505194 ER PT J AU Xu, Y Li, F Zalzala, M Xu, JS Gonzalez, FJ Adorini, L Lee, YK Yin, LY Zhang, YQ AF Xu, Yang Li, Fei Zalzala, Munaf Xu, Jiesi Gonzalez, Frank J. Adorini, Luciano Lee, Yoon-Kwang Yin, Liya Zhang, Yanqiao TI Farnesoid X receptor activation increases reverse cholesterol transport by modulating bile acid composition and cholesterol absorption in mice SO HEPATOLOGY LA English DT Article ID NEGATIVE FEEDBACK-REGULATION; FATTY LIVER-DISEASE; E-KNOCKOUT MICE; NUCLEAR RECEPTOR; LIPID HOMEOSTASIS; IN-VIVO; METABOLISM; PATHWAYS; FXR; ATHEROSCLEROSIS AB Activation of farnesoid X receptor (FXR) markedly attenuates development of atherosclerosis in animal models. However, the underlying mechanism is not well elucidated. Here, we show that the FXR agonist, obeticholic acid (OCA), increases fecal cholesterol excretion and macrophage reverse cholesterol transport (RCT) dependent on activation of hepatic FXR. OCA does not increase biliary cholesterol secretion, but inhibits intestinal cholesterol absorption. OCA markedly inhibits hepatic cholesterol 7-alpha hydroxylase (Cyp7a1) and sterol 12 alpha-hydroxylase (Cyp8b1) partly through inducing small heterodimer partner, leading to reduced bile acid pool size and altered bile acid composition, with the alpha/beta-muricholic acid proportion in bile increased by 2.6-fold and taurocholic acid (TCA) level reduced by 71%. Overexpression of Cyp8b1 or concurrent overexpression of Cyp7a1 and Cyp8b1 normalizes TCA level, bile acid composition, and intestinal cholesterol absorption. Conclusion: Activation of FXR inhibits intestinal cholesterol absorption by modulation of bile acid pool size and composition, thus leading to increased RCT. Targeting hepatic FXR and/or bile acids may be useful for boosting RCT and preventing the development of atherosclerosis. C1 [Xu, Yang; Zalzala, Munaf; Xu, Jiesi; Lee, Yoon-Kwang; Yin, Liya; Zhang, Yanqiao] Northeast Ohio Med Univ, Dept Integrat Med Sci, 4209 St,Route 44,POB 95, Rootstown, OH 44272 USA. [Li, Fei; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Zalzala, Munaf] Univ Baghdad, Coll Pharm, Dept Pharmacol & Toxicol, Baghdad, Iraq. [Adorini, Luciano] Intercept Pharmaceut, New York, NY USA. RP Yin, LY; Zhang, YQ (reprint author), Northeast Ohio Med Univ, Dept Integrat Med Sci, 4209 St,Route 44,POB 95, Rootstown, OH 44272 USA. EM lyin@neomed.edu; yzhang@neomed.edu FU NIH [R01HL103227, R01DK095895, R01DK102619] FX This work was supported by NIH grants R01HL103227, R01DK095895, and R01DK102619 (to Y.Z.). NR 43 TC 2 Z9 2 U1 13 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 IS 4 BP 1072 EP 1085 DI 10.1002/hep.28712 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DX7FP UT WOS:000384552300010 PM 27359351 ER PT J AU Bae, HR Leung, PSC Tsuneyama, K Valencia, JC Hodge, DL Kim, S Back, T Karwan, M Merchant, AS Baba, N Feng, DC Park, O Gao, B Yang, GX Gershwin, ME Young, HA AF Bae, Heekyong R. Leung, Patrick S. C. Tsuneyama, Koichi Valencia, Julio C. Hodge, Deborah L. Kim, Seohyun Back, Tim Karwan, Megan Merchant, Anand S. Baba, Nobuyuki Feng, Dechun Park, Ogyi Gao, Bin Yang, Guo-Xiang Gershwin, M. Eric Young, Howard A. TI Chronic Expression of Interferon-Gamma Leads to Murine Autoimmune Cholangitis With a Female Predominance SO HEPATOLOGY LA English DT Article ID PRIMARY BILIARY-CIRRHOSIS; GENOME-WIDE ASSOCIATION; DIFFERENTIAL GENE-EXPRESSION; ANTIMITOCHONDRIAL ANTIBODIES; T-CELLS; SUSCEPTIBILITY LOCI; IMMUNE-RESPONSES; EPITHELIAL-CELLS; ANIMAL-MODELS; RISK-FACTORS AB In most autoimmune diseases the serologic hallmarks of disease precede clinical pathology by years. Therefore, the use of animal models in defining early disease events becomes critical. We took advantage of a "designer" mouse with dysregulation of interferon gamma (IFN gamma) characterized by prolonged and chronic expression of IFN through deletion of the IFN gamma 3-untranslated region adenylate uridylate-rich element (ARE). The ARE-Del(-/-) mice develop primary biliary cholangitis (PBC) with a female predominance that mimics human PBC that is characterized by up-regulation of total bile acids, spontaneous production of anti-mitochondrial antibodies, and portal duct inflammation. Transfer of CD4 T cells from ARE-Del(-/-) to B6/Rag1(-/-) mice induced moderate portal inflammation and parenchymal inflammation, and RNA sequencing of liver gene expression revealed that up-regulated genes potentially define early stages of cholangitis. Interestingly, up-regulated genes specifically overlap with the gene expression signature of biliary epithelial cells in PBC, implying that IFN gamma may play a pathogenic role in biliary epithelial cells in the initiation stage of PBC. Moreover, differentially expressed genes in female mice have stronger type 1 and type 2 IFN gamma signaling and lymphocyte-mediated immune responses and thus may drive the female bias of the disease. Conclusion: Changes in IFN expression are critical for the pathogenesis of PBC. C1 [Bae, Heekyong R.; Valencia, Julio C.; Hodge, Deborah L.; Kim, Seohyun; Back, Tim; Young, Howard A.] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. [Leung, Patrick S. C.; Yang, Guo-Xiang; Gershwin, M. Eric] Univ Calif Davis, Sch Med, Div Rheumatol Allergy & Clin Immunol, Davis, CA 95616 USA. [Tsuneyama, Koichi] Univ Tokushima, Inst Biomed Sci, Dept Pathol & Lab Med, Grad Sch, Tokushima, Japan. [Karwan, Megan] NCI, Lab Anim Sci, Frederick, MD 21701 USA. [Merchant, Anand S.] NCI, CCR Collaborat Bioinformat Core, Bethesda, MD 20892 USA. [Baba, Nobuyuki] Kagawa Prefectural Cent Hosp, Cent Lab, Takamatsu, Kagawa, Japan. [Feng, Dechun; Gao, Bin] NIAAA, Lab Liver Dis, Rockville, MD 20852 USA. [Park, Ogyi] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. RP Young, HA (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.; Gershwin, ME (reprint author), Univ Calif Davis, Sch Med, Div Rheumatol Allergy & Clin Immunol, Davis, CA 95616 USA. FU National Institutes of Health grant [DK090019] FX Supported in part by National Institutes of Health grant DK090019 (to M.E.G.). NR 44 TC 3 Z9 3 U1 4 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 IS 4 BP 1189 EP 1201 DI 10.1002/hep.28641 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DX7FP UT WOS:000384552300018 PM 27178326 ER PT J AU Porat-Shliom, N Tietgens, AJ Van Itallie, CM Vitale-Cross, L Jarnik, M Harding, OJ Anderson, JM Gutkind, JS Weigert, R Arias, IM AF Porat-Shliom, Natalie Tietgens, Amber J. Van Itallie, Christina M. Vitale-Cross, Lynn Jarnik, Michal Harding, Olivia J. Anderson, James M. Gutkind, J. Silvio Weigert, Roberto Arias, Irwin M. TI Liver Kinase B1 Regulates Hepatocellular Tight Junction Distribution and Function In Vivo SO HEPATOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; HEPATOCYTE POLARIZATION; MITOCHONDRIAL FISSION; CELL POLARITY; LKB1; AMPK; PERMEABILITY; CINGULIN; PHOSPHORYLATION; BARRIER AB Liver kinase B1 (LKB1) and its downstream effector AMP-activated protein kinase (AMPK) play critical roles in polarity establishment by regulating membrane trafficking and energy metabolism. In collagen sandwich-cultured hepatocytes, loss of LKB1 or AMPK impaired apical ABCB11 (Bsep) trafficking and bile canalicular formation. In the present study, we used liver-specific (albumin-Cre) LKB1 knockout mice (LKB1(-/-)) to investigate the role of LKB1 in the maintenance of functional tight junction (TJ) in vivo. Transmission electron microscopy examination revealed that hepatocyte apical membrane with microvilli substantially extended into the basolateral domain of LKB1(-/-) livers. Immunofluorescence studies revealed that loss of LKB1 led to longer and wider canalicular structures correlating with mislocalization of the junctional protein, cingulin. To test junctional function, we used intravital microscopy to quantify the transport kinetics of 6-carboxyfluorescein diacetate (6-CFDA), which is processed in hepatocytes into its fluorescent derivative 6-carboxyfluorescein (6-CF) and secreted into the canaliculi. In LKB1(-/-) mice, 6-CF remained largely in hepatocytes, canalicular secretion was delayed, and 6-CF appeared in the blood. To test whether 6-CF was transported through permeable TJ, we intravenously injected low molecular weight (3 kDa) dextran in combination with 6-CFDA. In wild-type mice, 3 kDa dextran remained in the vasculature, whereas it rapidly appeared in the abnormal bile canaliculi in LKB1(-/-) mice, confirming that junctional disruption resulted in paracellular exchange between the blood stream and the bile canaliculus. Conclusion: LKB1 plays a critical role in regulating the maintenance of TJ and paracellular permeability, which may explain how various drugs, chemicals, and metabolic states that inhibit the LKB1/AMPK pathway result in cholestasis. C1 [Porat-Shliom, Natalie; Vitale-Cross, Lynn; Harding, Olivia J.; Gutkind, J. Silvio; Weigert, Roberto] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. [Porat-Shliom, Natalie; Weigert, Roberto] NCI, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA. [Tietgens, Amber J.; Van Itallie, Christina M.; Anderson, James M.] NHLBI, Lab Tight Junct Struct & Funct, Bldg 10, Bethesda, MD 20892 USA. [Jarnik, Michal; Arias, Irwin M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD USA. RP Porat-Shliom, N (reprint author), NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bldg 37,Room 2050B, Bethesda, MD 20892 USA. EM poratshliomn@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, National Institute of Dental and Craniofacial Research FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Dental and Craniofacial Research. NR 48 TC 3 Z9 3 U1 10 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 IS 4 BP 1317 EP 1329 DI 10.1002/hep.28724 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DX7FP UT WOS:000384552300027 PM 27396550 ER PT J AU Mandrekar, P Bataller, R Tsukamoto, H Gao, B AF Mandrekar, Pranoti Bataller, Ramon Tsukamoto, Hidekazu Gao, Bin TI Alcoholic Hepatitis: Translational Approaches to Develop Targeted Therapies SO HEPATOLOGY LA English DT Article ID INDUCED LIVER-INJURY; TUMOR-NECROSIS-FACTOR; MACROPHAGE ACTIVATION; BINGE ETHANOL; MICE; DISEASE; INFLAMMATION; STEATOSIS; CELL; STEATOHEPATITIS AB Alcoholic liver disease is a leading cause of liver-related mortality worldwide. In contrast to recent advances in therapeutic strategies for patients with viral hepatitis, there is a significant lack of novel therapeutic options for patients with alcoholic liver disease. In particular, there is an urgent need to focus our efforts on effective therapeutic interventions for alcoholic hepatitis (AH), the most severe form of alcoholic liver disease. AH is characterized by an abrupt development of jaundice and complications related to liver insufficiency and portal hypertension in patients with heavy alcohol intake. The mortality of patients with AH is very high (20%-50% at 3 months). Available therapies are not effective in many patients, and targeted approaches are imminently needed. The development of such therapies requires translational studies in human samples and suitable animal models that reproduce the clinical and histological features of AH. In recent years, new animal models that simulate some of the features of human AH have been developed, and translational studies using human samples have identified potential pathogenic factors and histological parameters that predict survival. Conclusion: This review summarizes the unmet needs for translational studies on the pathogenesis of AH, preclinical translational tools, and emerging drug targets to benefit the AH patient. C1 [Mandrekar, Pranoti] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. [Bataller, Ramon] Univ N Carolina, Div Gastroenterol & Hepatol, Dept Med, Chapel Hill, NC USA. [Bataller, Ramon] Univ N Carolina, Div Gastroenterol & Hepatol, Dept Nutr, Chapel Hill, NC USA. [Tsukamoto, Hidekazu] Univ Southern Calif, Greater Los Angeles Dept Vet Affairs Healthcare S, Southern Calif Res Ctr ALPD & Cirrhosis, Los Angeles, CA USA. [Tsukamoto, Hidekazu] Univ Southern Calif, Greater Los Angeles Dept Vet Affairs Healthcare S, Dept Pathol, Los Angeles, CA USA. [Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA. RP Gao, B (reprint author), NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA.; Mandrekar, P (reprint author), Univ Massachusetts, Med Ctr, Gastrointestinal Div, Dept Med, LRB Rm 221 364 Plantat St, Worcester, MA 01605 USA.; Bataller, R (reprint author), Univ North Carlina, Chapel Hill, NC 27599 USA.; Tsukamoto, H (reprint author), Univ South Calif, Los Angeles, CA 90089 USA. EM Pranoti.Mandrekar@umassmed.edu; ramon_bataller@med.unc.edu; htsukamo@med.usc.edu; bgao@mail.nih.gov FU Department of Defense [W81XWH-11-1-0420, W81XWH-13-1-0498]; National Institute on Alcohol Abuse and Alcoholism [5P50AA011999, 1U01AA018663, 5R24AA012885]; Department of Veterans Affairs Merit Review award [5I01BX001991]; National Institute on Alcohol Abuse and Alcoholism Intramural Program; [2AA017986-01]; [1U01AA021908-01]; [1U01AA020821] FX Supported by RO1 #2AA017986-01 and Department of Defense grants PRMRP #W81XWH-11-1-0420 and PRMRP#W81XWH-13-1-0498 (to P.M.); grants 1U01AA021908-01 and 1U01AA020821 (to R.B.); National Institute on Alcohol Abuse and Alcoholism grants 5P50AA011999, 1U01AA018663, and 5R24AA012885 and Department of Veterans Affairs Merit Review award 5I01BX001991 (to H.T.); and the National Institute on Alcohol Abuse and Alcoholism Intramural Program (to B.G.). NR 61 TC 6 Z9 6 U1 9 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 IS 4 BP 1343 EP 1355 DI 10.1002/hep.28530 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DX7FP UT WOS:000384552300029 PM 26940353 ER PT J AU Tang, DM Heller, T Koh, C AF Tang, Derek M. Heller, Theo Koh, Christopher TI The Many Faces of Positive Hepatitis B Surface Antigen SO HEPATOLOGY LA English DT Letter C1 [Tang, Derek M.; Koh, Christopher] NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. [Heller, Theo; Koh, Christopher] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. RP Tang, DM (reprint author), NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 DK999999] NR 5 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2016 VL 64 IS 4 BP 1379 EP 1381 DI 10.1002/hep.28503 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DX7FP UT WOS:000384552300043 PM 26890893 ER PT J AU Peng, GCY AF Peng, Grace C. Y. TI Moving Toward Model Reproducibility and Reusability SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Biological system modeling; biomedical computing; biomedical engineering; computational biology; computational modeling; computer simulation; reproducibility of results AB This paper provides a brief history of the U.S. funding initiatives associated with promoting multiscale modeling of the physiome since 2003. An effort led in the United States is the Interagency Modeling and Analysis Group (IMAG) Multiscale Modeling (MSM) Consortium. Though IMAG and the MSM Consortium have generated much interest in developing MSM models of the physiome, challenges associated with model and data sharing in biomedical, biological, and behavioral systems still exist. Since 2013, the IEEE EMBS Technical Committee on Computational Biology and the Physiome (CBaP TC) has supported discussions on promoting model reproducibility through publications. This special issue on model sharing and reproducibility is a realization of the CBaP TC discussions. Though open questions remain on how we can further facilitate model reproducibility, accessibility, and reuse by the worldwide community for different biomedical domain applications, this special issue provides a unique demonstration of both the challenges and opportunities for publishing reproducible computational models. C1 [Peng, Grace C. Y.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. RP Peng, GCY (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. EM grace.peng@nih.gov FU Intramural NIH HHS [Z99 EB999999] NR 8 TC 0 Z9 0 U1 3 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 EI 1558-2531 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD OCT PY 2016 VL 63 IS 10 BP 1997 EP 1998 DI 10.1109/TBME.2016.2603418 PG 2 WC Engineering, Biomedical SC Engineering GA DX7LZ UT WOS:000384570200002 PM 27576241 ER PT J AU Chan, JL Mazilu, D Miller, JG Hunt, T Horvath, KA Li, M AF Chan, Joshua L. Mazilu, Dumitru Miller, Justin G. Hunt, Timothy Horvath, Keith A. Li, Ming TI Robotic-assisted real-time MRI-guided TAVR: from system deployment to in vivo experiment in swine model SO INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY LA English DT Article DE Robotic assistance; MRI; Magnetic resonance; TAVR; Valve replacement; Cardiac surgery ID AORTIC-VALVE-REPLACEMENT; IMPLANTATION; STENOSIS; SURGERY; SAFETY; PROSTHESIS; PLACEMENT AB Real-time magnetic resonance imaging (rtMRI) guidance provides significant advantages during transcatheter aortic valve replacement (TAVR) as it provides superior real-time visualization and accurate device delivery tracking. However, performing a TAVR within an MRI scanner remains difficult due to a constrained procedural environment. To address these concerns, a magnetic resonance (MR)-compatible robotic system to assist in TAVR deployments was developed. This study evaluates the technical design and interface considerations of an MR-compatible robotic-assisted TAVR system with the purpose of demonstrating that such a system can be developed and executed safely and precisely in a preclinical model. An MR-compatible robotic surgical assistant system was built for TAVR deployment. This system integrates a 5-degrees of freedom (DoF) robotic arm with a 3-DoF robotic valve delivery module. A user interface system was designed for procedural planning and real-time intraoperative manipulation of the robot. The robotic device was constructed of plastic materials, pneumatic actuators, and fiber-optical encoders. The mechanical profile and MR compatibility of the robotic system were evaluated. The system-level error based on a phantom model was 1.14 +/- 0.33 mm. A self-expanding prosthesis was successfully deployed in eight Yorkshire swine under rtMRI guidance. Post-deployment imaging and necropsy confirmed placement of the stent within 3 mm of the aortic valve annulus. These phantom and in vivo studies demonstrate the feasibility and advantages of robotic-assisted TAVR under rtMRI guidance. This robotic system increases the precision of valve deployments, diminishes environmental constraints, and improves the overall success of TAVR. C1 [Chan, Joshua L.; Mazilu, Dumitru; Miller, Justin G.; Hunt, Timothy; Horvath, Keith A.; Li, Ming] NHLBI, Cardiothorac Surg Res Program, NIH, Bldg 10,Room B1D47,MSC 1550,10 Ctr Dr, Bethesda, MD 20892 USA. RP Li, M (reprint author), NHLBI, Cardiothorac Surg Res Program, NIH, Bldg 10,Room B1D47,MSC 1550,10 Ctr Dr, Bethesda, MD 20892 USA. EM Joshua.Chan@nih.gov; horvathka@nhlbi.nih.gov; lim2@mail.nih.gov OI Chan, Joshua/0000-0001-7220-561X FU Intramural Research Program of the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), US Department of Health and Human Services (DHHS) FX This research was made possible by funding from the Intramural Research Program of the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), US Department of Health and Human Services (DHHS) NR 39 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1861-6410 EI 1861-6429 J9 INT J COMPUT ASS RAD JI Int. J. Comput. Assist. Radiol. Surg. PD OCT PY 2016 VL 11 IS 10 BP 1905 EP 1918 DI 10.1007/s11548-016-1421-4 PG 14 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Engineering; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA DX7EP UT WOS:000384549700012 PM 27246950 ER PT J AU Lansford, JE Godwin, J Alampay, LP Tirado, LMU Zelli, A Al-Hassan, SM Bacchini, D Bombi, AS Bornstein, MH Chang, L Deater-Deckard, K Di Giunta, L Dodge, KA Malone, PS Oburu, P Pastorelli, C Skinner, AT Sorbring, E Tapanya, S AF Lansford, Jennifer E. Godwin, Jennifer Pena Alampay, Liane Uribe Tirado, Liliana Maria Zelli, Arnaldo Al-Hassan, Suha M. Bacchini, Dario Bombi, Anna Silvia Bornstein, Marc H. Chang, Lei Deater-Deckard, Kirby Di Giunta, Laura Dodge, Kenneth A. Malone, Patrick S. Oburu, Paul Pastorelli, Concetta Skinner, Ann T. Sorbring, Emma Tapanya, Sombat TI Mothers', fathers' and children's perceptions of parents' expectations about children's family obligations in nine countries SO INTERNATIONAL JOURNAL OF PSYCHOLOGY LA English DT Article DE Culture; Family obligations; Parent-child relationships; Parental attitudes ID EUROPEAN BACKGROUNDS; CULTURAL-VALUES; LATIN-AMERICAN; ADOLESCENTS; IMMIGRANT; ATTITUDES; PARENTIFICATION; ACCULTURATION; ADAPTATION; STUDENTS AB Children's family obligations involve assistance and respect that children are expected to provide to immediate and extended family members and reflect beliefs related to family life that may differ across cultural groups. Mothers, fathers and children (N = 1432 families) in 13 cultural groups in 9 countries (China, Colombia, Italy, Jordan, Kenya, Philippines, Sweden, Thailand and United States) reported on their expectations regarding children's family obligations and parenting attitudes and behaviours. Within families, mothers and fathers had more concordant expectations regarding children's family obligations than did parents and children. Parenting behaviours that were warmer, less neglectful and more controlling as well as parenting attitudes that were more authoritarian were related to higher expectations regarding children's family obligations between families within cultures as well as between cultures. These international findings advance understanding of children's family obligations by contextualising them both within families and across a number of diverse cultural groups in 9 countries. C1 [Lansford, Jennifer E.; Godwin, Jennifer; Dodge, Kenneth A.; Malone, Patrick S.; Skinner, Ann T.] Duke Univ, Ctr Child & Family Policy, Box 90545, Durham, NC 27708 USA. [Pena Alampay, Liane] Ateneo Manila Univ, Dept Psychol, Quezon City, Philippines. [Uribe Tirado, Liliana Maria] Univ San Buenaventura, Consultorio Psicol Popular, Medellin, Colombia. [Zelli, Arnaldo] Univ Rome Foro Italico, Dept Educ Sci, Rome, Italy. [Al-Hassan, Suha M.] Hashemite Univ, Queen Rania Fac Childhood, Zarqa, Jordan. [Al-Hassan, Suha M.] Emirates Coll Adv Educ, Hlth & Special Educ Div, Abu Dhabi, U Arab Emirates. [Bacchini, Dario] Univ Naples 2, Dept Psychol, Caserta, Italy. [Bombi, Anna Silvia; Di Giunta, Laura; Pastorelli, Concetta] Univ Roma La Sapienza, Fac Psychol, Rome, Italy. [Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Child & Family Res Program Dev Neurosci, Bethesda, MD USA. [Chang, Lei] Hong Kong Inst Educ, Dept Psychol Studies, Hong Kong, Hong Kong, Peoples R China. [Deater-Deckard, Kirby] Virginia Polytech Inst & State Univ, Dept Psychol, Blacksburg, VA 24061 USA. [Oburu, Paul] Maseno Univ, Dept Educ Psychol, Maseno, Kenya. [Sorbring, Emma] Univ West, Dept Psychol, Trollhattan, Sweden. [Tapanya, Sombat] Chiang Mai Univ, Dept Psychiat, Chiang Mai, Thailand. RP Lansford, JE (reprint author), Duke Univ, Ctr Child & Family Policy, Box 90545, Durham, NC 27708 USA. EM lansford@duke.edu OI ZELLI, Arnaldo/0000-0003-4020-8159 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [RO1-HD054805]; Fogarty International Center [RO3-TW008141]; Intramural Research Program of the NIH/NICHD FX This research has been funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development grant RO1-HD054805 and Fogarty International Center grant RO3-TW008141. This research was also supported by the Intramural Research Program of the NIH/NICHD. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or NICHD. Lansford designed the study and drafted the Introduction and Discussion sections of this article. Godwin conducted the statistical analyses and drafted the Methods and Results sections. All other authors contributed to the overall study design and data collection, provided critical feedback on the manuscript and approved the final submitted version. NR 25 TC 1 Z9 1 U1 5 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0020-7594 EI 1464-066X J9 INT J PSYCHOL JI Int. J. Psychol. PD OCT PY 2016 VL 51 IS 5 BP 366 EP 374 DI 10.1002/ijop.12185 PG 9 WC Psychology, Multidisciplinary SC Psychology GA DW4NV UT WOS:000383620900006 PM 26104262 ER PT J AU O'Brien, F Gormley, M AF O'Brien, Fearghal Gormley, Michael TI Risk-perception and dangerous driving among adolescents: Outcome- and behavior-focused questions yield opposite results SO JOURNAL OF ADOLESCENCE LA English DT Article DE Dangerous driving; Adolescence; Risk taking; Risk perception; Question focus ID YOUNG-ADULTS; SMOKING; AGE AB While some studies have found that those who perceive a behavior to be more risky are less likely to engage in it, others have found that those who engage in more risky behaviors see themselves as being more at-risk. Using an online questionnaire we investigated whether such conflicting findings may be due to the types of risk-questions employed in past studies. We assessed risk-perception using outcome-focused questions (e.g. the likelihood of being in an accident) and a behavior-focused question (the riskiness of speeding). Participants who reported engaging in more risky driving gave higher estimates of their chances of experiencing a negative outcome. However, those same participants gave lower estimates of the general riskiness of risky driving. Drivers may think about the risks of risky driving in different ways depending on the focus of the questions. Published by Elsevier Ltd on behalf of The Foundation for Professionals in Services for Adolescents. C1 [O'Brien, Fearghal] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd, Bethesda, MD 20892 USA. [Gormley, Michael] Trinity Coll Dublin, Sch Psychol, Dublin 2, Ireland. RP O'Brien, F (reprint author), NICHHD, Div Intramural Populat Hlth Res, 6100 Execut Blvd,Room 7B13L, Bethesda, MD 20892 USA. EM obrienfk@tcd.ie FU School of Psychology, Trinity College, Dublin; Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This research was supported by the School of Psychology, Trinity College, Dublin and by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 21 TC 0 Z9 0 U1 6 U2 6 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0140-1971 EI 1095-9254 J9 J ADOLESCENCE JI J. Adolesc. PD OCT PY 2016 VL 52 BP 89 EP 94 DI 10.1016/j.adolescence.2016.07.010 PG 6 WC Psychology, Developmental SC Psychology GA DY0IO UT WOS:000384780700010 PM 27518903 ER PT J AU Yeboah, J Rodriguez, CJ Qureshi, W Liu, ST Carr, JJ Lima, JA Hundley, WG Herrington, DM AF Yeboah, Joseph Rodriguez, Carlos J. Qureshi, Waqas Liu, Songtao Carr, J. Jeffrey Lima, Joao A. Hundley, W. Gregory Herrington, David M. TI Prognosis of Low Normal Left Ventricular Ejection Fraction in an Asymptomatic Population-Based Adult Cohort: The Multiethnic Study of Atherosclerosis SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Low normal left ventricular ejection fraction; congestive heart failure; death; prognosis; prevalence ID HEART-FAILURE; MYOCARDIAL-INFARCTION; SYSTOLIC DYSFUNCTION; ETHNIC-MINORITIES; MANAGEMENT; TRIAL AB Background: Reduced left ventricular systolic function predicts worse outcomes. However, the optimal threshold for "normal" left ventricular ejection fraction (LVEF) is uncertain. In general, LVEF >= 55% is considered to be "normal" by guidelines, with a low normal designation for LVEF being 50%-55%. We assessed the prognosis of participants with low normal LVEF in the Multiethnic Study of Atherosclerosis. All participants were asymptomatic and had no known clinical cardiovascular disease at baseline. Methods and Results: A total of 4926 out of 6814 had LVEF assessed with the use of cardiac magnetic resonance imaging (MRI), had no significant valvular disease, did not have myocardial infarction during follow-up, had complete data, and were included in this analysis. A total of 83/4926 (1.7%) had LVEF <50% (low LVEF) and 101/4926 (2.1%) had low normal LVEF. Cox proportional hazard and cubic spline analyses were used to evaluate the association between LVEF category and 10 years of adjudicated incident congestive heart failure (CHF) and all-cause mortality adjusting for (model 1) age, sex, and race and (model 2) model 1 and diabetes mellitus, smoking, systolic blood pressure (BP), BP medications, body mass index, estimated glomerular filtration rate, low-density lipoprotein, family history of coronary heart disease, educational status, and LV mass. Mean age was 61 +/- 10 years, 47% were men, 35% were on BP medications, 9% had diabetes. After 10.2 years of follow-up, 109 (2.2%) had CHF and 427 (8.7%) died. Compared with normal LVEF (>= 55%), low normal LVEF and low LVEF were associated with an increased risk for incident CHF during follow-up in our multivariable Cox models: hazard ratios (HRs) 3.64 (95% CI 1.76-7.52) and 9.52 (5.63-17.52), respectively. Unlike low LVEF, low normal LVEF was not associated with increased risk of death compared with normal LVEF in our fully adjusted models: HRs 3.03 (1.94-1.73) and 1.32 (0.72-2.41), respectively. In the adjusted spline analysis HR of LVEF 55% as reference, LVEF had a U-shape association of future CHF risk and LVEF. Conclusion: Low normal LVEF is as prevalent as low LVEF in asymptomatic community-dwelling adults. We observed a gradient-response association between the 3 categories of LVEF (low, low normal, and normal) and incident CHF but not for all-cause death. C1 [Yeboah, Joseph; Rodriguez, Carlos J.; Qureshi, Waqas; Hundley, W. Gregory; Herrington, David M.] Wake Forest Univ, Sch Med, Heart & Vasc Ctr Excellence, Winston Salem, NC 27109 USA. [Yeboah, Joseph; Rodriguez, Carlos J.] Wake Forest Sch Med, Epidemiol & Prevent, Winston Salem, NC USA. [Liu, Songtao] NIH, Bldg 10, Bethesda, MD 20892 USA. [Carr, J. Jeffrey] Vanderbilt Univ, Sch Med, Cardiol & Radiol, Nashville, TN 37212 USA. [Lima, Joao A.] Johns Hopkins Univ, Cardiol & Radiol, Baltimore, MD USA. RP Yeboah, J (reprint author), Wake Forest Sch Med, Heart & Vasc Ctr Excellence, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM jyeboah@wakehealth.edu OI Carr, John/0000-0002-4398-8237 FU National Heart, Lung, and Blood Institute [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]; National Center for Research Resources [UL1-TR-000040, UL1-RR-025005] FX This research was supported by 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 and N01-HC-95169 from the National Heart, Lung, and Blood Institute and by grants UL1-TR-000040 and UL1-RR-025005 from National Center for Research Resources. NR 18 TC 2 Z9 2 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD OCT PY 2016 VL 22 IS 10 BP 763 EP 768 DI 10.1016/j.cardfail.2016.03.013 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DY0JG UT WOS:000384782500004 PM 27038640 ER PT J AU Lexmond, WS Goettel, JA Lyons, JJ Jacobse, J Deken, MM Lawrence, MG DiMaggio, TH Kotlarz, D Garabedian, E Sackstein, P Nelson, CC Jones, N Stone, KD Candotti, F Rings, EHHM Thrasher, AJ Milner, JD Snapper, SB Fiebiger, E AF Lexmond, Willem S. Goettel, Jeremy A. Lyons, Jonathan J. Jacobse, Justin Deken, Marion M. Lawrence, Monica G. DiMaggio, Thomas H. Kotlarz, Daniel Garabedian, Elizabeth Sackstein, Paul Nelson, Celeste C. Jones, Nina Stone, Kelly D. Candotti, Fabio Rings, Edmond H. H. M. Thrasher, Adrian J. Milner, Joshua D. Snapper, Scott B. Fiebiger, Edda TI FOXP3(+) Tregs require WASP to restrain Th2-mediated food allergy SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID WISKOTT-ALDRICH-SYNDROME; REGULATORY T-CELLS; SYNDROME PROTEIN WASP; MAST-CELLS; IN-VIVO; ANTIGEN RECEPTOR; TYPE-2 IMMUNITY; NATIONAL-HEALTH; IGE LEVELS; MICE AB In addition to the infectious consequences of immunodeficiency, patients with Wiskott-Aldrich syndrome (WAS) often suffer from poorly understood exaggerated immune responses that result in autoimmunity and elevated levels of serum IgE. Here, we have shown that WAS patients and mice deficient in WAS protein (WASP) frequently develop IgE-mediated reactions to common food allergens. WASP-deficient animals displayed an adjuvant-free IgE-sensitization to chow antigens that was most pronounced for wheat and soy and occurred under specific pathogen-free as well as germ-free housing conditions. Conditional deletion of Was in FOXP3(+) Tregs resulted in more severe Th2-type intestinal inflammation than that observed in mice with global WASP deficiency, indicating that allergic responses to food allergens are dependent upon loss of WASP expression in this immune compartment. While WASP-deficient Tregs efficiently contained Th1- and Th17-type effector differentiation in vivo, they failed to restrain Th2 effector responses that drive allergic intestinal inflammation. Loss of WASP was phenotypically associated with increased GATA3 expression in effector memory FOXP3(+) Tregs, but not in naive like FOXP3(+) Tregs, an effect that occurred independently of increased IL-4 signaling. Our results reveal a Treg-specific role for WASP that is required for prevention of Th2 effector cell differentiation and allergic sensitization to dietary antigens. C1 [Lexmond, Willem S.; Goettel, Jeremy A.; Jacobse, Justin; Deken, Marion M.; Kotlarz, Daniel; Snapper, Scott B.; Fiebiger, Edda] Boston Childrens Hosp, Div Gastroenterol Hepatol & Nutr, Dept Pediat, Boston, MA USA. [Lexmond, Willem S.; Goettel, Jeremy A.; Snapper, Scott B.; Fiebiger, Edda] Harvard Med Sch, Dept Med, Boston, MA USA. [Lyons, Jonathan J.; DiMaggio, Thomas H.; Sackstein, Paul; Nelson, Celeste C.; Milner, Joshua D.] NIAID, Genet & Pathogenesis Allergy Sect, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Lawrence, Monica G.] Univ Virginia Hlth Syst, Dept Med, Div Asthma Allergy & Immunol, Charlottesville, VA USA. [Kotlarz, Daniel] Univ Munich, Dr von Hauner Childrens Hosp, Dept Pediat, Munich, Germany. [Garabedian, Elizabeth] NHGRI, NIH, Bethesda, MD 20892 USA. [Jones, Nina] NCI, Clin Res Directorate, CMRP, Leidos Biomed Res Inc, Campus & Frederick, Frederick, MD 21701 USA. [Stone, Kelly D.] NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Candotti, Fabio] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Rings, Edmond H. H. M.] Erasmus Univ, Erasmus Med Ctr, Dept Pediat, Rotterdam, Netherlands. [Rings, Edmond H. H. M.] Leiden Univ, Univ Med Ctr Leiden, Leiden, Netherlands. [Thrasher, Adrian J.] Great Ormond St Hosp NHS Trust, London, England. [Thrasher, Adrian J.] UCL, Inst Child Hlth, London, England. [Snapper, Scott B.] Brigham & Womens Hosp, Dept Med, Div Gastroenterol, 75 Francis St, Boston, MA 02115 USA. RP Snapper, SB (reprint author), 300 Longwood Ave,EN670, Boston, MA 02115 USA.; Fiebiger, E (reprint author), 300 Longwood Ave,EN626, Boston, MA 02115 USA. EM scott.snapper@childrens.harvard.edu; edda.fiebiger@childrens.harvard.edu OI Jacobse, Justin/0000-0002-1899-0319 FU National Institutes of Health [HL59561, DK034854, AI50950, AI075037]; Crohn's and Colitis Foundation of America [CDA 352644]; Harvard Digestive Diseases Center [P30DK034854]; Helmsley Charitable Trust; Wolpow Family Chair in IBD Treatment and Research; Wellcome Trust; Division of Intramural Research of the NIAID; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; NHGRI, NIH FX We thank Oliver T. Burton and all members of the Fiebiger laboratory and Snapper laboratory for discussion and technical assistance, and Stefano Volpi and Luigi Notarangelo at Boston Children's Hospital for providing serum samples. The patient cohort study benefitted from technical assistance and supply of equipment and reagents by Lisa Workman and Thomas A. E. Platts-Mills. This work was supported by grants from the National Institutes of Health: HL59561, DK034854, and AI50950 (to SBS), and AI075037 (to EF). This work was further supported by a senior research grant of the Crohn's and Colitis Foundation of America (to EF), an unrestricted gift from the Mead Johnson Nutrition Company (to WSL and EF), the Crohn's and Colitis Foundation of America CDA 352644 (to JAG), and the Harvard Digestive Diseases Center grant P30DK034854. Additional support was provided by the Helmsley Charitable Trust and the Wolpow Family Chair in IBD Treatment and Research (to SBS), and the Wellcome Trust (to AJT). Funding for clinical patient studies was provided in part by the Division of Intramural Research of the NIAID and NHGRI, 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. NR 63 TC 3 Z9 3 U1 3 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2016 VL 126 IS 10 BP 4030 EP 4044 DI 10.1172/JCI85129 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DX9HD UT WOS:000384703300037 PM 27643438 ER PT J AU Krieter, P Chiang, N Gyaw, S Skolnick, P Crystal, R Keegan, F Aker, J Beck, M Harris, J AF Krieter, Philip Chiang, Nora Gyaw, Shwe Skolnick, Phil Crystal, Roger Keegan, Fintan Aker, Julie Beck, Melissa Harris, Jennifer TI Pharmacokinetic Properties and Human Use Characteristics of an FDA-Approved Intranasal Naloxone Product for the Treatment of Opioid Overdose SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE intranasal; naloxone; opioid overdose; pharmacokinetics; Narcan (R) Nasal Spray ID INTRAMUSCULAR NALOXONE; HEALTHY-VOLUNTEERS; SEX-DIFFERENCES; UNITED-STATES; NASAL; DRUG; HYDROCHLORIDE; EDUCATION; METHADONE; PITFALLS AB Parenteral naloxone has been approved to treat opiate overdose for over 4 decades. Intranasal naloxone, administered off label using improvised devices, has been widely used by both first responders and the lay public to treat overdose. However, these improvised devices require training for effective use, and the recommended volumes (2 to 4 mL) exceed those considered optimum for intranasal administration. The present study compared the pharmacokinetic properties of intranasal naloxone (2 to 8 mg) delivered in low volumes (0.1 to 0.2 mL) using an Aptar Unit-Dose device to an approved (0.4 mg) intramuscular dose. A parallel study assessed the ease of use of this device in a simulated overdose situation. All doses of intranasal naloxone resulted in plasma concentrations and areas under the curve greater than those observed following the intramuscular dose; the time to reach maximum plasma concentrations was not different following intranasal and intramuscular administration. Plasma concentrations of naloxone were dose proportional between 2 and 8 mg and independent of whether drug was administered to 1 or both nostrils. In a study using individuals representative of the general population, >90% were able to perform both critical tasks (inserting nozzle into a nostril and pressing plunger) needed to deliver a simulated dose of naloxone without prior training. Based on both pharmacokinetic and human use studies, a 4-mg dose delivered in a single device (0.1 mL) was selected as the final product. This product can be used by first responders and the lay public, providing an important and potentially life-saving intervention for victims of an opioid overdose. C1 [Krieter, Philip; Chiang, Nora; Gyaw, Shwe; Skolnick, Phil] NIDA, NIH, Bethesda, MD 20892 USA. [Crystal, Roger] Lightlake Therapeut, New York, NY USA. [Keegan, Fintan] Adapt Pharma Ltd, Dublin, Ireland. [Aker, Julie; Beck, Melissa; Harris, Jennifer] Concentr Res, Indianapolis, IN USA. RP Skolnick, P (reprint author), NIDA, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM phil.skolnick@nih.gov FU Lightlake Therapeutics; Adapt Pharma; NIDA [N01DA-12-8905, N01DA-13-8920, N01DA-14-8914] FX R.C. is an employee of Lightlake Therapeutics. F.K. is an employee of Adapt Pharma, Ltd. J.A., M.B., and J.H. are employees of Concentrics Research. P.K., N.C., S.G., and P.S. are employees of the National Institutes of Health. The work was supported in part by Lightlake Therapeutics, Adapt Pharma, and NIDA contracts N01DA-12-8905, N01DA-13-8920, and N01DA-14-8914. NR 33 TC 1 Z9 1 U1 7 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0091-2700 EI 1552-4604 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD OCT PY 2016 VL 56 IS 10 BP 1243 EP 1253 DI 10.1002/jcph.759 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DX7DD UT WOS:000384545600008 PM 27145977 ER PT J AU Pabayo, R Dunn, EC Gilman, SE Kawachi, I Molnar, BE AF Pabayo, Roman Dunn, Erin C. Gilman, Stephen E. Kawachi, Ichiro Molnar, Beth E. TI Income inequality within urban settings and depressive symptoms among adolescents SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article DE SOCIAL EPIDEMIOLOGY; SOCIAL INEQUALITIES; DEPRESSION ID RISK BEHAVIOR SURVEILLANCE; UNITED-STATES; MENTAL-HEALTH; NEIGHBORHOOD CHARACTERISTICS; SOCIOECONOMIC-STATUS; MULTILEVEL ANALYSIS; GENDER-DIFFERENCES; LEVEL; DISORDER; VIOLENCE AB Background Although recent evidence has shown that area-level income inequality is related to increased risk for depression among adults, few studies have tested this association among adolescents. Methods We analysed the cross-sectional data from a sample of 1878 adolescents living in 38 neighbourhoods participating in the 2008 Boston Youth Survey. Using multilevel linear regression modelling, we: (1) estimated the association between neighbourhood income inequality and depressive symptoms, (2) tested for cross-level interactions between sex and neighbourhood income inequality and (3) examined neighbourhood social cohesion as a mediator of the relationship between income inequality and depressive symptoms. Results The association between neighbourhood income inequality and depressive symptoms varied significantly by sex, with girls in higher income inequality neighbourhood reporting higher depressive symptom scores, but not boys. Among girls, a unit increase in Gini Z-score was associated with more depressive symptoms (=0.38, 95% CI 0.28 to 0.47, p=0.01) adjusting for nativity, neighbourhood income, social cohesion, crime and social disorder. There was no evidence that the association between income inequality and depressive symptoms was due to neighbourhood-level differences in social cohesion. Conclusions The distribution of incomes within an urban area adversely affects adolescent girls' mental health; future work is needed to understand why, as well as to examine in greater depth the potential consequences of inequality for males, which may have been difficult to detect here. C1 [Pabayo, Roman] Univ Nevada, Sch Community Hlth Sci, 1664 North Virginia St, Reno, NV 89557 USA. [Pabayo, Roman; Gilman, Stephen E.; Kawachi, Ichiro] Harvard TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA. [Dunn, Erin C.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Dunn, Erin C.] Harvard Med Sch, Dept Psychiat, Boston, MA USA. [Dunn, Erin C.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Boston, MA USA. [Gilman, Stephen E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Hlth Behav Branch, Div Intramural Populat Hlth Res, Rockville, MD USA. [Molnar, Beth E.] Northeastern Univ, Bouve Coll Hlth Sci, Boston, MA 02115 USA. RP Pabayo, R (reprint author), Univ Nevada, Sch Community Hlth Sci, 1664 North Virginia St, Reno, NV 89557 USA. EM rpabayo@unr.edu OI Gilman, Stephen/0000-0002-8331-6419 FU Centers for Disease Control and Prevention (CDC); National Center for Injury Prevention and Control (NCIPC) [U49CE00740]; Canadian Institutes of Health Research [234617]; National Institute Of Mental Health of the National Institutes of Health [K01MH102403]; Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development FX The Boston Youth Survey (BYS) was conducted in collaboration with the Boston Public Health Commission (Barbara Ferrer, Executive Director), Boston's Office of Human Services (Larry Mayes, Chief), Boston Public Schools (Carol Johnson, Superintendent) and the Office of The Honorable Mayor Thomas M. Menino. The survey would not have been possible without the participation of the faculty, staff, administrators, and students of Boston Public Schools. This work was supported by a grant from the Centers for Disease Control and Prevention (CDC), National Center for Injury Prevention and Control (NCIPC) (U49CE00740) to the Harvard Youth Violence Prevention Center (David Hemenway, Principal Investigator). During this analysis, Roman Pabayo was a Canadian Institutes of Health Research postdoctoral fellowship recipient # 234617. Research reported in this publication was also supported, in part, by the National Institute Of Mental Health of the National Institutes of Health under Award Number K01MH102403 (Dunn) and by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 50 TC 0 Z9 0 U1 12 U2 12 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X EI 1470-2738 J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD OCT PY 2016 VL 70 IS 10 BP 997 EP 1003 DI 10.1136/jech-2015-206613 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DX5RJ UT WOS:000384439100009 PM 27103664 ER PT J AU Raghavan, S Pachucki, MC Chang, YC Porneala, B Fox, CS Dupuis, J Meigs, JB AF Raghavan, Sridharan Pachucki, Mark C. Chang, Yuchiao Porneala, Bianca Fox, Caroline S. Dupuis, Josee Meigs, James B. TI Incident Type 2 Diabetes Risk is Influenced by Obesity and Diabetes in Social Contacts: a Social Network Analysis SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE type 2 diabetes; social network; obesity; family history; epidemiology ID PREDICTION; SELECTION; BEHAVIOR; FRIENDS; COHORT; ADULTS AB Obesity and diabetes family history are the two strongest risk factors for type 2 diabetes (T2D). Prior work shows that an individual's obesity risk is associated with obesity in social contacts, but whether T2D risk follows similar patterns is unknown. We aimed to estimate the relationship between obesity or diabetes in an individual's social contacts and his/her T2D risk. We hypothesized that obesity and diabetes in social contacts would increase an individual's T2D risk. This was a retrospective analysis of the community-based Framingham Offspring Study (FOS). FOS participants with T2D status, height and weight, and at least one social contact were eligible for this study (n = 4797 at Exam 1). Participants' interpersonal ties, cardiometabolic and demographic variables were available at eight exams from 1971 to 2008, and a T2D additive polygenic risk score was measured at the fifth exam. Primary exposures were T2D (fasting glucose aeyen 7 mmol/L or taking diabetes medications) and obesity status (BMI aeyen 30 kg/m(2)) of social contacts at a prior exam. Primary outcome was incident T2D in participants. Incident T2D was associated with having a social contact with diabetes (OR 1.32, p = 0.004) or with obesity (OR 1.21, p = 0.004). In stratified analyses, incident T2D was associated with diabetes in siblings (OR 1.64, p = 0.001) and obesity in spouses (OR 1.54, p = 0.0004). The associations between diabetes and obesity in social contacts and an individual's incident diabetes risk were stronger in individuals with a high diabetes genetic risk score. T2D and obesity in social contacts, particularly siblings and spouses, were associated with an individual's risk of incident diabetes even after accounting for parental T2D history. Assessing risk factors in an individual's siblings and spouses can inform T2D risk; furthermore, social network based lifestyle interventions involving spouses and siblings might be a novel T2D prevention approach. C1 [Raghavan, Sridharan; Chang, Yuchiao; Porneala, Bianca; Meigs, James B.] Harvard Med Sch, Dept Med, Div Gen Internal Med, Boston, MA 02115 USA. [Raghavan, Sridharan; Chang, Yuchiao; Porneala, Bianca; Meigs, James B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Raghavan, Sridharan] Eastern Colorado Hlth Care Syst, Dept Vet Affairs Med Ctr, Denver, CO USA. [Raghavan, Sridharan] Univ Colorado, Sch Med, Dept Med, Div Gen Internal Med, Denver, CO USA. [Pachucki, Mark C.] Univ Massachusetts, Dept Sociol, Computat Social Sci Inst, Amherst, MA 01003 USA. [Fox, Caroline S.] NHLBI, Lab Metab & Populat Hlth, Framingham, MA USA. [Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA. RP Meigs, JB (reprint author), Harvard Med Sch, Dept Med, Div Gen Internal Med, Boston, MA 02115 USA.; Meigs, JB (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jmeigs@partners.org FU NIH National Research Service Award [T32HP10251]; Ryoichi Sasakawa Fellowship Fund; NIH [RO1DK78616]; National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; [K24 DK080140] FX SR is supported by NIH National Research Service Award T32HP10251 and the Ryoichi Sasakawa Fellowship Fund. JBM and JD are supported by NIH RO1DK78616, and JBM is also supported by K24 DK080140. We gratefully acknowledge the FHS study participants and staff for their contributions. This work was partially supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195) and its contract with Affymetrix, Inc for genotyping services (Contract No. N02-HL-6-4278). NR 31 TC 2 Z9 2 U1 10 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2016 VL 31 IS 10 BP 1127 EP 1133 DI 10.1007/s11606-016-3723-1 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DW4FF UT WOS:000383597200006 PM 27145760 ER PT J AU Schapira, MM Sprague, BL Klabunde, CN Tosteson, ANA Bitton, A Chen, JS Beaber, EF Onega, T MacLean, CD Harris, K Howe, K Pearson, L Feldman, S Brawarsky, P Haas, JS AF Schapira, Marilyn M. Sprague, Brian L. Klabunde, Carrie N. Tosteson, Anna N. A. Bitton, Asaf Chen, Jane S. Beaber, Elisabeth F. Onega, Tracy MacLean, Charles D. Harris, Kimberly Howe, Kathleen Pearson, Loretta Feldman, Sarah Brawarsky, Phyllis Haas, Jennifer S. CA PROSPR Consortium TI Inadequate Systems to Support Breast and Cervical Cancer Screening in Primary Care Practice SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT Annual Research Meeting of the Academy-Health CY JUN, 2015 CL Minneapolis, MN SP Acad Hlth DE breast cancer screening; cervical cancer screening; patient-centered medical home ID CENTERED MEDICAL HOME; QUALITY-OF-CARE; PREVENTIVE SERVICES; PHYSICIANS; PARTICIPATION; INTERVENTIONS; METAANALYSIS; IMPROVEMENT; STRATEGIES; CONTEXT AB Despite substantial resources devoted to cancer screening nationally, the availability of clinical practice-based systems to support screening guidelines is not known. To characterize the prevalence and correlates of practice-based systems to support breast and cervical cancer screening, with a focus on the patient-centered medical home (PCMH). Web and mail survey of primary care providers conducted in 2014. The survey assessed provider (gender, training) and facility (size, specialty training, physician report of National Committee for Quality Assurance (NCQA) PCMH recognition, and practice affiliation) characteristics. A hierarchical multivariate analysis clustered by clinical practice was conducted to evaluate characteristics associated with the adoption of practice-based systems and technology to support guideline-adherent screening. Primary care physicians in family medicine, general internal medicine, and obstetrics and gynecology, and nurse practitioners or physician assistants from four clinical care networks affiliated with PROSPR (Population-based Research Optimizing Screening through Personalized Regimens) consortium research centers. The prevalence of routine breast cancer risk assessment, electronic health record (EHR) decision support, comparative performance reports, and panel reports of patients due for routine screening and follow-up. There were 385 participants (57.6 % of eligible). Forty-seven percent (47.0 %) of providers reported NCQA recognition as a PCMH. Less than half reported EHR decision support for breast (48.8 %) or cervical cancer (46.2 %) screening. A minority received comparative performance reports for breast (26.2 %) or cervical (19.7 %) cancer screening, automated reports of patients overdue for breast (18.7 %) or cervical (16.4 %) cancer screening, or follow-up of abnormal breast (18.1 %) or cervical (17.6 %) cancer screening tests. In multivariate analysis, reported NCQA recognition as a PCMH was associated with greater use of comparative performance reports of guideline-adherent breast (OR 3.23, 95 % CI 1.58-6.61) or cervical (OR 2.56, 95 % CI 1.32-4.96) cancer screening and automated reports of patients overdue for breast (OR 2.19, 95 % CI 1.15-41.7) or cervical (OR. 2.56, 95 % CI 1.26-5.26) cancer screening. Providers lack systems to support breast and cervical cancer screening. Practice transformation toward a PCMH may support the adoption of systems to achieve guideline-adherent cancer screening in primary care settings. C1 [Schapira, Marilyn M.] Univ Penn, 1110 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. [Schapira, Marilyn M.] Philadelphia VA Med Ctr, 1110 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. [Sprague, Brian L.; MacLean, Charles D.; Howe, Kathleen] Univ Vermont, Burlington, VT USA. [Klabunde, Carrie N.] NIH, Off Dis Prevent, Off Director, Bldg 10, Bethesda, MD 20892 USA. [Tosteson, Anna N. A.; Onega, Tracy; Pearson, Loretta] Geisel Sch Med Dartmouth, Lebanon, NH USA. [Tosteson, Anna N. A.; Onega, Tracy; Pearson, Loretta] Norris Cotton Canc Ctr, Lebanon, NH USA. [Bitton, Asaf; Feldman, Sarah] Harvard Med Sch, Boston, MA USA. [Bitton, Asaf; Chen, Jane S.; Harris, Kimberly; Feldman, Sarah; Brawarsky, Phyllis] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Beaber, Elisabeth F.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Haas, Jennifer S.] Brigham & Womens Hosp, Div Gen Internal Med & Primary Care, 75 Francis St, Boston, MA 02115 USA. RP Schapira, MM (reprint author), Univ Penn, 1110 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA.; Schapira, MM (reprint author), Philadelphia VA Med Ctr, 1110 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM mschap@upenn.edu FU NCI NIH HHS [U54 CA163303, P30 CA023108, U01 CA163304, U54 CA163307, U54 CA163313] NR 39 TC 1 Z9 1 U1 8 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2016 VL 31 IS 10 BP 1148 EP 1155 DI 10.1007/s11606-016-3726-y PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA DW4FF UT WOS:000383597200009 PM 27251058 ER PT J AU Benjamini, D Basser, PJ AF Benjamini, Dan Basser, Peter J. TI Use of marginal distributions constrained optimization (MADCO) for accelerated 2D MRI relaxometry and diffusometry SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE Fredholm integral; Inverse problems; Relaxometry; Diffusometry; Reconstruction; Multidimensional; Distribution ID MAGNETIZATION-TRANSFER; 1ST KIND; RELAXATION; T-1; INVERSION; GRADIENT; NERVE; BRAIN AB Measuring multidimensional (e.g., 2D) relaxation spectra in NMR and MRI clinical applications is a holy grail of the porous media and biomedical MR communities. The main bottleneck is the inversion of Fredholm integrals of the first kind, an ill-conditioned problem requiring large amounts of data to stabilize a solution. We suggest a novel experimental design and processing framework to accelerate and improve the reconstruction of such 2D spectra that uses a priori information from the 1D projections of spectra, or marginal distributions. These 1D marginal distributions provide powerful constraints when 2D spectra are reconstructed, and their estimation requires an order of magnitude less data than a conventional 2D approach. This marginal distributions constrained optimization (MADCO) methodology is demonstrated here with a polyvinylpyrrolidone-water phantom that has 3 distinct peaks in the 2D D-T1 space. The stability, sensitivity to experimental parameters, and accuracy of this new approach are compared with conventional methods by serially subsampling the full data set. While the conventional, unconstrained approach performed poorly, the new method had proven to be highly accurate and robust, only requiring a fraction of the data. Additionally, synthetic T1-T2 data are presented to explore the effects of noise on the estimations, and the performance of the proposed method with a smooth and realistic 2D spectrum. The proposed framework is quite general and can also be used with a variety of 2D MRI experiments (D-T2, T1-T2, D-D, etc.), making these potentially feasible for preclinical and even clinical applications for the first time. Published by Elsevier Inc. C1 [Benjamini, Dan; Basser, Peter J.] NICHD, Quantitat Imaging & Tissue Sci, NIH, Bethesda, MD 20892 USA. RP Benjamini, D (reprint author), NICHD, Quantitat Imaging & Tissue Sci, NIH, Bethesda, MD 20892 USA. EM dan.benjamini@nih.gov FU Intramural Research Program of The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) FX This work was supported by funds provided by the Intramural Research Program of The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The authors thank Dr. Martin Lizak for writing the IR-DWI pulse sequence, Dr. Jian Cheng for providing fruitful discussions, and Ms. Liz Salak for editing the manuscript. NR 19 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 EI 1096-0856 J9 J MAGN RESON JI J. Magn. Reson. PD OCT PY 2016 VL 271 BP 40 EP 45 DI 10.1016/j.jmr.2016.08.004 PG 6 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA DX8JN UT WOS:000384634000006 PM 27543810 ER PT J AU Riscuta, G AF Riscuta, Gabriela TI Nutrigenomics at the Interface of Aging, Lifespan, and Cancer Prevention SO JOURNAL OF NUTRITION LA English DT Review DE nutrigenomics; diet; aging; longevity; DNA repair; telomere; cancer; caloric restriction; oxidative stress ID TELOMERE LENGTH; CALORIC RESTRICTION; COLORECTAL-CANCER; OXIDATIVE STRESS; MISMATCH REPAIR; RHESUS-MONKEYS; DNA-REPAIR; HEALTH; DISEASE; DIET AB The percentage of elderly people with associated age-related health deterioration, including cancer, has been increasing for decades. Among age-related diseases, the incidence of cancer has grown substantially, in part because of the overlap of some molecular pathways between cancer and aging. Studies with model organisms suggest that aging and age related conditions are manipulable processes that can be modified by both genetic and environmental factors, including dietary habits. Variations in genetic backgrounds likely lead to differential responses to dietary changes and account for some of the inconsistencies found in the literature. The intricacies of the aging process, coupled with the interrelational role of bioactive food components on gene expression, make this review a complex undertaking. Nevertheless, intriguing evidence suggests that dietary habits can manipulate the aging process and/or its consequences and potentially may have unprecedented health benefits. The present review focuses on 4 cellular events: telomerase activity, bioenergetics, DNA repair, and oxidative stress. These processes are linked to both aging and cancer risk, and their alteration in animal models by selected food components is evident. C1 [Riscuta, Gabriela] NCI, Nutr Sci Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. RP Riscuta, G (reprint author), NCI, Nutr Sci Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. EM gabriela.riscuta@nih.gov NR 79 TC 0 Z9 0 U1 19 U2 19 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 EI 1541-6100 J9 J NUTR JI J. Nutr. PD OCT PY 2016 VL 146 IS 10 BP 1931 EP 1939 DI 10.3945/jn.116.235119 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA DY0KE UT WOS:000384784900002 PM 27558581 ER PT J AU Tikkanen, R Saukkonen, T Fex, M Bennet, H Rautiainen, MR Paunio, T Koskinen, M Panarsky, R Bevilacqua, L Sjoberg, RL Tiihonen, J Virkkunen, M AF Tikkanen, Roope Saukkonen, Tero Fex, Malin Bennet, Hedvig Rautiainen, Marja-Riitta Paunio, Tiina Koskinen, Mika Panarsky, Rony Bevilacqua, Laura Sjoberg, Rickard L. Tiihonen, Jari Virkkunen, Matti TI The effects of a HTR2B stop codon and testosterone on energy metabolism and beta cell function among antisocial Finnish males SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE ASPD; 5-HT2B receptor; HTR2B; Testosterone; Insulin resistance; BMI ID VIOLENT ALCOHOLIC OFFENDERS; BROWN ADIPOSE-TISSUE; BODY-MASS INDEX; INSULIN-SECRETION; AUTORECEPTOR GENE; SEROTONIN; OBESITY; RESISTANCE; POLYMORPHISM; CONSUMPTION AB Herein, we examined insulin resistance (IR), insulin sensitivity (IS), beta cell activity, and glucose metabolism in subjects with antisocial personality disorder (ASPD), and whether the serotonin 2B (5-HT2B) receptor and testosterone have a role in energy metabolism. A cohort of subjects belonging to a founder population that included 98 ASPD males, aged 25-30, was divided into groups based on the presence of a heterozygous 5-HT2B receptor loss-of-function gene mutation (HTR2B Q20*; n = 9) or not (n = 89). Serum glucose and insulin levels were measured in a 5 h oral glucose tolerance test (75 g) and indices describing IR, IS, and beta cell activity were calculated. Body mass index (BMI) was also determined. Concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid were measured in cerebrospinal fluid, and testosterone levels from serum. An IR-like state comprising high IR, low IS, and high beta cell activity indices was observed among ASPD subjects without the HTR2B Q20* allele. By contrast, being an ASPD HTR2B Q20* carrier appeared to be preventive of these pathophysiologies. The HTR2B Q20* allele and testosterone predicted lower BMI independently, but an interaction between HTR2B Q20* and testosterone lead to increased insulin sensitivity among HTR2B Q20* carriers with low testosterone levels. The HTR2B Q20* allele also predicted reduced beta cell activity and enhanced glucose metabolism. Reduced 5-HT2B receptor function at low or normal testosterone levels may be protective of obesity. Results were observed among Finnish males having an antisocial personality disorder, which limits the generality. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Tikkanen, Roope; Paunio, Tiina; Virkkunen, Matti] Univ Helsinki, Helsinki Univ Cent Hosp, Dept Psychiat, Helsinki, Finland. [Tikkanen, Roope] Rinnekoti Fdn, Res & Dev, Espoo, Finland. [Saukkonen, Tero] Helsinki Univ Cent Hosp, Childrens Hosp, Helsinki, Finland. [Saukkonen, Tero] Univ Helsinki, Helsinki, Finland. [Saukkonen, Tero] Novo Nordisk Farma Oy, Espoo, Finland. [Fex, Malin; Bennet, Hedvig] Lund Univ, Ctr Diabet, Dept Clin Sci, Scania Univ Hosp, Malmo, Sweden. [Rautiainen, Marja-Riitta; Paunio, Tiina; Tiihonen, Jari] Natl Inst Hlth & Welf, Helsinki, Finland. [Koskinen, Mika] Oy Aava Dev Ltd, Helsinki, Finland. [Panarsky, Rony] NIAAA, Neurogenet Lab, Bethesda, MD USA. [Bevilacqua, Laura] NYU, Sch Med, Dept Psychiat, New York, NY USA. [Sjoberg, Rickard L.] Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden. [Tiihonen, Jari] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. [Tiihonen, Jari] Univ Eastern Finland, Niuvanniemi Hosp, Dept Forens Psychiat, Kuopio, Finland. RP Tikkanen, R (reprint author), Univ Helsinki, Dept Psychiat, Valskarinkatu 12,POB 22, Helsinki 00260, Finland. EM roope.tikkanen@gmail.com FU Orion Research Foundation; Swedish Research Council [2012-1552]; Waldemar von Frenckell Foundation FX This work was supported by the Orion Research Foundation, Swedish Research Council (project number: 2012-1552 to M.F), and Waldemar von Frenckell Foundation. Excellence in diabetes research (EXODIAB), Krapperup foundation, Ake Wiberg foundation, Royal Physiographic Society, Albert Pahlsson foundation, Crafoord foundation, Childhood Diabetes Foundation, and the Foundation of Sigurd and Elsa Golijes Minne. NR 45 TC 0 Z9 0 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 EI 1879-1379 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD OCT PY 2016 VL 81 BP 79 EP 86 DI 10.1016/j.jpsychires.2016.06.019 PG 8 WC Psychiatry SC Psychiatry GA DY1LB UT WOS:000384855400011 PM 27420381 ER PT J AU Dember, LM Archdeacon, P Krishnan, M Lacson, E Ling, SM Roy-Chaudhury, P Smith, KA Flessner, MF AF Dember, Laura M. Archdeacon, Patrick Krishnan, Mahesh Lacson, Eduardo, Jr. Ling, Shari M. Roy-Chaudhury, Prabir Smith, Kimberly A. Flessner, Michael F. TI Pragmatic Trials in Maintenance Dialysis: Perspectives from the Kidney Health Initiative SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID CLINICAL-TRIALS; QUALITY; CARE; NEPHROLOGY; CLINICALTRIALS.GOV; INCREASE; CONSENT; POLICY; SAFETY; PBRN AB Pragmatic clinical trials are conducted under the real-world conditions of clinical care delivery. As a result, these trials yield findings that are highly generalizable to the nonresearch setting, identify interventions that are readily translatable into clinical practice, and cost less than trials that require extensive research infrastructures. Maintenance dialysis is a setting especially well suited for pragmatic trials because of inherently frequent and predictable patient encounters, highly granular and uniform data collection, use of electronic data systems, and delivery of care by a small number of provider organizations to approximately 90% of patients nationally. Recognizing the potential for pragmatic trials to generate much needed evidence to guide the care of patients receiving maintenance dialysis, the Kidney Health Initiative assembled a group of individuals with relevant expertise from academia, industry, and government to provide the nephrology community with information about the design and conduct of such trials, with a specific focus on the dialysis setting. Here, we review this information, and where applicable, use experience from the ongoing Time to Reduce Mortality in End Stage Renal Disease Trial, a large cluster-randomized, pragmatic trial evaluating hemodialysis session duration, to illustrate challenges and solutions to operational, ethical, and regulatory issues. C1 [Dember, Laura M.] Univ Penn, Renal Electrolyte & Hypertens Div, Perelman Sch Med, Philadelphia, PA 19104 USA. [Dember, Laura M.] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Archdeacon, Patrick] US FDA, Off Med Policy, Silver Spring, MD USA. [Archdeacon, Patrick; Smith, Kimberly A.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Krishnan, Mahesh] DaVita Healthcare Partners, Denver, CO USA. [Lacson, Eduardo, Jr.] Tufts Med Ctr, Div Nephrol, Boston, MA USA. [Lacson, Eduardo, Jr.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Ling, Shari M.] Ctr Medicare Serv, Ctr Clin Stand & Qual, Baltimore, MD USA. [Ling, Shari M.] Ctr Medicaid Serv, Ctr Clin Stand & Qual, Baltimore, MD USA. [Roy-Chaudhury, Prabir] Univ Arizona, Coll Med, Div Nephrol, Tucson, AZ USA. [Roy-Chaudhury, Prabir] Southern Arizona Vet Adm Hlth Care Syst, Tucson, AZ USA. [Flessner, Michael F.] NIDDK, Div Kidney Urol & Hematol, Bethesda, MD 20892 USA. RP Dember, LM (reprint author), Univ Penn, Perelman Sch Med, Blockley Hall,Room 920,423 Guardian Dr, Philadelphia, PA 19104 USA. EM ldember@upenn.edu FU Kidney Health Initiative (KHI); American Society of Nephrology; US Food and Drug Administration; National Institutes of Health Office of the Director; National Institute of Diabetes and Digestive and Kidney Diseases [UH2-AT007797, UH3-DK102384] FX This work was supported by the Kidney Health Initiative (KHI), a public-private partnership between the American Society of Nephrology, the US Food and Drug Administration, and >75 member organizations and companies to enhance patient safety and foster innovation in kidney disease. KHI funds were used to defray costs incurred during the conduct of the project, including project management support which was expertly provided by American Society of Nephrology staff members, Melissa West and Ryan Murray. There was no honorarium or other financial support provided to KHI workgroup members. The authors of this paper had final review authority and are fully responsible for its content.; KHI makes every effort to avoid actual, potential, or perceived conflicts of interest that may arise as a result of industry relationships or personal interests among the members of the workgroup. More information on KHI, the workgroup, or the conflict of interest policy can be found at www.kidneyhealthinitiative.org. The TiME Trial is funded by the National Institutes of Health Office of the Director and the National Institute of Diabetes and Digestive and Kidney Diseases (UH2-AT007797 and UH3-DK102384 to L.M.D.). The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of any agency of the US Government, DaVita Healthcare Partners, or Fresenius Medical Care. NR 43 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 2016 VL 27 IS 10 BP 2955 EP 2963 DI 10.1681/ASN.2016030340 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA DX8HK UT WOS:000384628500008 PM 27401689 ER PT J AU Bodonyi-Kovacs, G Ma, JZ Chang, J Lipkowitz, MS Kopp, JB Winkler, CA Le, TH AF Bodonyi-Kovacs, Gabor Ma, Jennie Z. Chang, Jamison Lipkowitz, Michael S. Kopp, Jeffrey B. Winkler, Cheryl Ann Le, Thu H. TI Combined Effects of GSTM1 Null Allele and APOL1 Renal Risk Alleles in CKD Progression in the African American Study of Kidney Disease and Hypertension Trial SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GENE POLYMORPHISM; VARIANTS; NEPHROPATHY; METAANALYSIS; ASSOCIATION; GENOTYPE; DECLINE; AASK AB Apolipoprotein L-1 (APOL1) high risk alleles and the glutathione-S-transferase-mu 1 (GSTM1) null allele have been shown separately to associate with CKD progression in the African American Study of Kidney Disease and Hypertension (AASK) trial participants. Here, we determined combined effects of GSTM1 null and APOL1 high risk alleles on clinical outcomes in 682 AASK participants who were classified into four groups by GSTM1 null or active genotype and APOL1 high or low risk genotype. We assessed survival differences among these groups by log-rank test and Cox regression adjusted for important clinical variables for time to GFR event (change in GFR of 50% or 25-ml/min per 1.73 m(2) decline), incident ESRD, death, or composite outcomes. The groups differed significantly in event-free survival for incident ESRD and composite outcomes (P <= 0.001 by log-rank test). Compared with the reference GSTM1 active/APOL1 low risk group, other groups had these hazard ratios for the composite outcome of incident ESRD and change in GFR: GSTM1 active/APOL1 high risk hazard ratio, 2.13; 95% confidence interval, 0.76 to 5.90 (P=0.15); GSTM1 null/APOL1 low risk hazard ratio, 2.05; 95% confidence interval, 1.08 to 3.88 (P=0.03); and GSTM1 null/APOL1 high risk hazard ratio, 3.0; 95% confidence interval, 1.51 to 5.96 (P=0.002). In conclusion, GSTM1 null and APOL1 high risk alleles deleteriously affect CKD progression among blacks with hypertension, and subjects with both GSTM1 null and APOL1 high risk genotypes had highest risk of adverse renal outcomes. Larger cohorts are needed to fully explore interactions of GSTM1 and APOL1 genotypes in other subgroups. C1 [Bodonyi-Kovacs, Gabor; Chang, Jamison; Le, Thu H.] Univ Virginia, Dept Med, Div Nephrol, Charlottesville, VA USA. [Ma, Jennie Z.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA. [Lipkowitz, Michael S.] Georgetown Univ, Dept Med, Div Nephrol, Washington, DC USA. [Kopp, Jeffrey B.] NIDDK, Kidney Dis Branch, NIH, Bethesda, MD 20892 USA. [Winkler, Cheryl Ann] NCI, Basic Res Lab, Ctr Canc Res, NIH,Leidos Biomed Inc,Frederick Natl Lab, Frederick, MD 21701 USA. RP Le, TH (reprint author), Univ Virginia, Box 800133, Charlottesville, VA 22908 USA. EM thl4t@virginia.edu FU Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH); National Cancer Institute, NIH, Center for Cancer Research [HHSN26120080001E]; NIH [R01DK094907-01] FX This work was supported, in part, by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH). This project has been funded, in whole or in part, with federal funds from National Cancer Institute, NIH, Center for Cancer Research contract HHSN26120080001E and in part, by NIH extramural grant R01DK094907-01 (to T.H.L). NR 25 TC 0 Z9 0 U1 3 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 2016 VL 27 IS 10 BP 3140 EP 3152 DI 10.1681/ASN.2015050487 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA DX8HK UT WOS:000384628500023 PM 26940095 ER PT J AU Lee, CP Liu, GT Kung, HN Liu, PT Liao, YT Chow, LP Chang, LS Chang, YH Chang, CW Shu, WC Angers, A Farina, A Lin, SF Tsai, CH Bouamr, F Chen, MR AF Lee, Chung-Pei Liu, Guan-Ting Kung, Hsiu-Ni Liu, Po-Ting Liao, Yen-Tzu Chow, Lu-Ping Chang, Ling-Shih Chang, Yu-Hsin Chang, Chou-Wei Shu, Wen-Chi Angers, Annie Farina, Antonella Lin, Su-Fang Tsai, Ching-Hwa Bouamr, Fadila Chen, Mei-Ru TI The Ubiquitin Ligase Itch and Ubiquitination Regulate BFRF1-Mediated Nuclear Envelope Modification for Epstein-Barr Virus Maturation SO JOURNAL OF VIROLOGY LA English DT Article ID PORE COMPLEX; L-DOMAIN; PROTEINS; TYPE-1; CELLS; FAMILY; EFFICIENT; BREAKDOWN; RELEASE; ESCRTS AB The cellular endosomal sorting complex required for transport (ESCRT) was recently found to mediate important morphogenesis processes at the nuclear envelope (NE). We previously showed that the Epstein-Barr virus (EBV) BFRF1 protein recruits the ESCRT-associated protein Alix to modulate NE structure and promote EBV nuclear egress. Here, we uncover new cellular factors and mechanisms involved in this process. BFRF1-induced NE vesicles are similar to those observed following EBV reactivation. BFRF1 is ubiquitinated, and elimination of possible ubiquitination by either lysine mutations or fusion of a deubiquitinase hampers NE-derived vesicle formation and virus maturation. While it interacts with multiple Nedd4-like ubiquitin ligases, BFRF1 preferentially binds Itch ligase. We show that Itch associates with Alix and BFRF1 and is required for BFRF1-induced NE vesicle formation. Our data demonstrate that Itch, ubiquitin, and Alix control the BFRF1-mediated modulation of the NE and EBV maturation, uncovering novel regulatory mechanisms of nuclear egress of viral nucleocapsids. IMPORTANCE The nuclear envelope (NE) of eukaryotic cells not only serves as a transverse scaffold for cellular processes, but also as a natural barrier for most DNA viruses that assemble their nucleocapsids in the nucleus. Previously, we showed that the cellular endosomal sorting complex required for transport (ESCRT) machinery is required for the nuclear egress of EBV. Here, we further report the molecular interplay among viral BFRF1, the ESCRT adaptor Alix, and the ubiquitin ligase Itch. We found that BFRF1-induced NE vesicles are similar to those observed following EBV reactivation. The lysine residues and the ubiquitination of BFRF1 regulate the formation of BFRF1-induced NE-derived vesicles and EBV maturation. During the process, a ubiquitin ligase, Itch, preferably associates with BFRF1 and is required for BFRF1-induced NE vesicle formation. Therefore, our data indicate that Itch, ubiquitin, and Alix control the BFRF1-mediated modulation of the NE, suggesting novel regulatory mechanisms for ESCRT-mediated NE modulation. C1 [Lee, Chung-Pei; Liu, Guan-Ting] Natl Taipei Univ Nursing & Hlth Sci, Sch Nursing, Taipei, Taiwan. [Liu, Guan-Ting; Liu, Po-Ting; Liao, Yen-Tzu; Chang, Ling-Shih; Chang, Yu-Hsin; Chang, Chou-Wei; Shu, Wen-Chi; Tsai, Ching-Hwa; Chen, Mei-Ru] Natl Taiwan Univ, Grad Inst, Coll Med, Taipei, Taiwan. [Liu, Guan-Ting; Liu, Po-Ting; Liao, Yen-Tzu; Chang, Ling-Shih; Chang, Yu-Hsin; Chang, Chou-Wei; Shu, Wen-Chi; Tsai, Ching-Hwa; Chen, Mei-Ru] Natl Taiwan Univ, Dept Microbiol, Coll Med, Taipei, Taiwan. [Kung, Hsiu-Ni] Natl Taiwan Univ, Dept Anat & Cell Biol, Coll Med, Taipei, Taiwan. [Chow, Lu-Ping] Natl Taiwan Univ, Grad Inst Med Genom & Prote, Coll Med, Taipei, Taiwan. [Angers, Annie] Univ Montreal, Dept Biol Sci, Montreal, PQ, Canada. [Farina, Antonella] Sapienza Univ Rome, Dept Expt Med, Rome, Italy. [Lin, Su-Fang] Inst Canc Res, Natl Hlth Res Inst, Taipei, Taiwan. [Bouamr, Fadila] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Chen, MR (reprint author), Natl Taiwan Univ, Grad Inst, Coll Med, Taipei, Taiwan.; Chen, MR (reprint author), Natl Taiwan Univ, Dept Microbiol, Coll Med, Taipei, Taiwan. EM mrc@ntu.edu.tw OI Farina, Antonella/0000-0002-8629-0971; Angers, Annie/0000-0003-0131-256X FU National Health Research Institutes (NHRI) [NHRI-EX104-10201BI]; National Taiwan University; Ministry of Science and Technology, Taiwan (MOST) [MOST102-2320-B-227-002, MOST103-2320-B-227-001-MY3] FX This work, including the efforts of Mei-Ru Chen, Chou-Wei Chang, and Wen-Chi Shu, was funded by National Health Research Institutes (NHRI) (NHRI-EX104-10201BI). This work, including the efforts of Mei-Ru Chen, Chou-Wei Chang, and Wen-Chi Shu, was funded by National Taiwan University (intramural grant). This work, including the efforts of Chung-Pei Lee, Guan-Ting Liu, Po-Ting Liu, Ling-Shih Chang, and Yu-Hsin Chang, was funded by Ministry of Science and Technology, Taiwan (MOST) (MOST102-2320-B-227-002 and MOST103-2320-B-227-001-MY3). NR 40 TC 2 Z9 2 U1 3 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD OCT PY 2016 VL 90 IS 20 BP 8994 EP 9007 DI 10.1128/JVI.01235-16 PG 14 WC Virology SC Virology GA DX7NO UT WOS:000384574900017 PM 27466427 ER PT J AU Ajiro, M Tang, S Doorbar, J Zheng, ZM AF Ajiro, Masahiko Tang, Shuang Doorbar, John Zheng, Zhi-Ming TI Serine/Arginine-Rich Splicing Factor 3 and Heterogeneous Nuclear Ribonucleoprotein A1 Regulate Alternative RNA Splicing and Gene Expression of Human Papillomavirus 18 through Two Functionally Distinguishable cis Elements SO JOURNAL OF VIROLOGY LA English DT Article ID SPINAL MUSCULAR-ATROPHY; TRACT BINDING-PROTEIN; MESSENGER-RNA; SR PROTEINS; FACTOR SRP20; MOUSE MODEL; HNRNP A1; CERVICAL-CANCER; DOWN-REGULATION; EXON SEQUENCES AB Human papillomavirus 18 (HPV18) is the second most common oncogenic HPV type associated with cervical, anogenital, and oropharyngeal cancers. Like other oncogenic HPVs, HPV18 encodes two major (one early and one late) polycistronic premRNAs that are regulated by alternative RNA splicing to produce a repertoire of viral transcripts for the expression of individual viral genes. However, RNA cis-regulatory elements and trans-acting factors contributing to HPV18 alternative RNA splicing remain unknown. In this study, an exonic splicing enhancer (ESE) in the nucleotide (nt) 3520 to 3550 region in the HPV18 genome was identified and characterized for promotion of HPV18 929 boolean AND 3434 splicing and E1 boolean AND E4 production through interaction with SRSF3, a host oncogenic splicing factor differentially expressed in epithelial cells and keratinocytes. Introduction of point mutations in the SRSF3-binding site or knockdown of SRSF3 expression in cells reduces 929 boolean AND 3434 splicing and E1 boolean AND E4 production but activates other, minor 929 boolean AND 3465 and 929 boolean AND 3506 splicing. Knockdown of SRSF3 expression also enhances the expression of E2 and L1 mRNAs. An exonic splicing silencer (ESS) in the HPV18 nt 612 to 639 region was identified as being inhibitory to the 233 boolean AND 416 splicing of HPV18 E6E7 pre-mRNAs via binding to hnRNP A1, a well-characterized, abundantly and ubiquitously expressed RNA-binding protein. Introduction of point mutations into the hnRNP A1-binding site or knockdown of hnRNP A1 expression promoted 233 boolean AND 416 splicing and reduced E6 expression. These data provide the first evidence that the alternative RNA splicing of HPV18 pre-mRNAs is subject to regulation by viral RNA cis elements and host trans-acting splicing factors. IMPORTANCE Expression of HPV18 genes is regulated by alternative RNA splicing of viral polycistronic pre-mRNAs to produce a repertoire of viral early and late transcripts. RNA cis elements and trans-acting factors contributing to HPV18 alternative RNA splicing have been discovered in this study for the first time. The identified ESS at the E7 open reading frame (ORF) prevents HPV18 233 boolean AND 416 splicing in the E6 ORF through interaction with a host splicing factor, hnRNP A1, and regulates E6 and E7 expression of the early E6E7 polycistronic pre-mRNA. The identified ESE at the E1 boolean AND E4 ORF promotes HPV18 929 boolean AND 3434 splicing of both viral early and late pre-mRNAs and E1 boolean AND E4 production through interaction with SRSF3. This study provides important observations on how alternative RNA splicing of HPV18 pre-mRNAs is subject to regulation by viral RNA cis elements and host splicing factors and offers potential therapeutic targets to overcome HPV-related cancer. C1 [Ajiro, Masahiko; Tang, Shuang; Zheng, Zhi-Ming] NCI, Tumor Virus RNA Biol Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res,NIH, Frederick, MD 21701 USA. [Doorbar, John] Univ Cambridge, Dept Pathol, Div Virol, Cambridge, England. [Ajiro, Masahiko] Kyoto Univ, Grad Sch Med, Dept Anat & Dev Biol, Dept Drug Discovery Med, Kyoto, Japan. [Tang, Shuang] US FDA, Div Viral Prod, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Silver Spring, MD USA. RP Zheng, ZM (reprint author), NCI, Tumor Virus RNA Biol Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res,NIH, Frederick, MD 21701 USA. EM zhengt@exchange.nih.gov FU HHS \ NIH \ NIH Office of the Director (OD) [1ZIASC010357]; HHS \ NIH \ Intramural Research Program FX This work, including the efforts of Zhi-Ming Zheng, was funded by HHS vertical bar NIH vertical bar NIH Office of the Director (OD) (1ZIASC010357). This work was funded by HHS vertical bar NIH vertical bar Intramural Research Program. NR 87 TC 1 Z9 1 U1 7 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD OCT PY 2016 VL 90 IS 20 BP 9138 EP 9152 DI 10.1128/JVI.00965-16 PG 15 WC Virology SC Virology GA DX7NO UT WOS:000384574900002 PM 27489271 ER PT J AU Turnbull, ML Wise, HM Nicol, MQ Smith, N Dunfee, RL Beard, PM Jagger, BW Ligertwood, Y Hardisty, GR Xiao, HX Benton, DJ Coburn, AM Paulo, JA Gygi, SP McCauley, JW Taubenberger, JK Lycett, SJ Weekes, MP Dutia, BM Digard, P AF Turnbull, Matthew L. Wise, Helen M. Nicol, Marlynne Q. Smith, Nikki Dunfee, Rebecca L. Beard, Philippa M. Jagger, Brett W. Ligertwood, Yvonne Hardisty, Gareth R. Xiao, Haixia Benton, Donald J. Coburn, Alice M. Paulo, Joao A. Gygi, Steven P. McCauley, John W. Taubenberger, Jeffery K. Lycett, Samantha J. Weekes, Michael P. Dutia, Bernadette M. Digard, Paul TI Role of the B Allele of Influenza A Virus Segment 8 in Setting Mammalian Host Range and Pathogenicity SO JOURNAL OF VIROLOGY LA English DT Article ID COMPLETE GENOME SEQUENCE; NS1 PROTEIN; NUCLEAR EXPORT; GENETIC-CHARACTERIZATION; NONSTRUCTURAL PROTEIN-1; PLASMA-MEMBRANE; BETA-INTERFERON; SOUTHERN CHINA; MESSENGER-RNAS; AMINO-ACID AB Two alleles of segment 8 (NS) circulate in nonchiropteran influenza A viruses. The A allele is found in avian and mammalian viruses, but the B allele is viewed as being almost exclusively found in avian viruses. This might reflect the fact that one or both of its encoded proteins (NS1 and NEP) are maladapted for replication in mammalian hosts. To test this, a number of clade A and B avian virus-derived NS segments were introduced into human H1N1 and H3N2 viruses. In no case was the peak virus titer substantially reduced following infection of various mammalian cell types. Exemplar reassortant viruses also replicated to similar titers in mice, although mice infected with viruses with the avian virus-derived segment 8s had reduced weight loss compared to that achieved in mice infected with the A/Puerto Rico/8/1934 (H1N1) parent. In vitro, the viruses coped similarly with type I interferons. Temporal proteomics analysis of cellular responses to infection showed that the avian virus-derived NS segments provoked lower levels of expression of interferon-stimulated genes in cells than wild type-derived NS segments. Thus, neither the A nor the B allele of avian virus-derived NS segments necessarily attenuates virus replication in a mammalian host, although the alleles can attenuate disease. Phylogenetic analyses identified 32 independent incursions of an avian virus-derived A allele into mammals, whereas 6 introductions of a B allele were identified. However, A-allele isolates from birds outnumbered B-allele isolates, and the relative rates of Aves-to-Mammalia transmission were not significantly different. We conclude that while the introduction of an avian virus segment 8 into mammals is a relatively rare event, the dogma of the B allele being especially restricted is misleading, with implications in the assessment of the pandemic potential of avian influenza viruses. IMPORTANCE Influenza A virus (IAV) can adapt to poultry and mammalian species, inflicting a great socioeconomic burden on farming and health care sectors. Host adaptation likely involves multiple viral factors. Here, we investigated the role of IAV segment 8. Segment 8 has evolved into two distinct clades: the A and B alleles. The B-allele genes have previously been suggested to be restricted to avian virus species. We introduced a selection of avian virus A-and B-allele segment 8s into human H1N1 and H3N2 virus backgrounds and found that these reassortant viruses were fully competent in mammalian host systems. We also analyzed the currently available public data on the segment 8 gene distribution and found surprisingly little evidence for specific avian host restriction of the B-clade segment. We conclude that B-allele segment 8 genes are, in fact, capable of supporting infection in mammals and that they should be considered during the assessment of the pandemic risk of zoonotic influenza A viruses. C1 [Turnbull, Matthew L.; Wise, Helen M.; Nicol, Marlynne Q.; Smith, Nikki; Beard, Philippa M.; Ligertwood, Yvonne; Hardisty, Gareth R.; Lycett, Samantha J.; Dutia, Bernadette M.; Digard, Paul] Univ Edinburgh, Div Infect & Immun, Roslin Inst, Edinburgh, Midlothian, Scotland. [Dunfee, Rebecca L.; Jagger, Brett W.; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, Div Intramural Res, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Jagger, Brett W.] Univ Cambridge, Div Virol, Dept Pathol, Cambridge, England. [Xiao, Haixia; Benton, Donald J.; McCauley, John W.] Francis Crick Inst, Mill Hill Lab, Mill Hill, London, England. [Coburn, Alice M.] Univ Glasgow, Ctr Virus Res, Glasgow, Lanark, Scotland. [Paulo, Joao A.; Gygi, Steven P.] Harvard Med Sch, Dept Cell Biol, Boston, MA USA. [Weekes, Michael P.] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England. [Wise, Helen M.] Heriot Watt Univ, Dept Engn & Phys Sci, Edinburgh, Midlothian, Scotland. [Xiao, Haixia] Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Lab Prot Engn & Vaccines, Tianjin, Peoples R China. RP Digard, P (reprint author), Univ Edinburgh, Div Infect & Immun, Roslin Inst, Edinburgh, Midlothian, Scotland. EM paul.digard@roslin.ed.ac.uk OI Lycett, Samantha/0000-0003-3159-596X FU Wellcome Trust [108070/Z/15/Z]; Medical Research Council (MRC) [MR/K000276/1]; Biotechnology and Biological Sciences Research Council (BBSRC) [BB/J004324/1, BB/J01446X/1]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases (DIR, NIAID); University Of Edinburgh FX This work, including the efforts of Michael P. Weekes, was funded by Wellcome Trust (108070/Z/15/Z). This work, including the efforts of Paul Digard, was funded by Medical Research Council (MRC) (MR/K000276/1). This work, including the efforts of Helen M. Wise, Philippa Beard, Samantha J. Lycett, Bernadette Dutia, and Paul Digard, was funded by Biotechnology and Biological Sciences Research Council (BBSRC) (BB/J004324/1). This work, including the efforts of Matthew L. Turnbull, was funded by Biotechnology and Biological Sciences Research Council (BBSRC) (BB/J01446X/1). This work, including the efforts of Jeffery K. Taubenberger, was funded by Division of Intramural Research, National Institute of Allergy and Infectious Diseases (DIR, NIAID). This work, including the efforts of Samantha J. Lycett, was funded by University Of Edinburgh (Chancellor's Fellowship). NR 99 TC 0 Z9 0 U1 8 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD OCT PY 2016 VL 90 IS 20 BP 9263 EP 9284 DI 10.1128/JVI.01205-16 PG 22 WC Virology SC Virology GA DX7NO UT WOS:000384574900041 PM 27489273 ER PT J AU Jager, J Mahler, A An, D Putnick, DL Bornstein, MH Lansford, JE Dodge, KA Skinner, AT Deater-Deckard, K AF Jager, Justin Mahler, Alissa An, Danming Putnick, Diane L. Bornstein, Marc H. Lansford, Jennifer E. Dodge, Kenneth A. Skinner, Ann T. Deater-Deckard, Kirby TI Early Adolescents' Unique Perspectives of Maternal and Paternal Rejection: Examining Their Across-Dyad Generalizability and Relations with Adjustment 1 Year Later SO JOURNAL OF YOUTH AND ADOLESCENCE LA English DT Article DE Unique perspectives; Parental rejection; Internalizing; Externalizing; Early adolescence ID PARENTAL ACCEPTANCE-REJECTION; FAMILY-MEMBERS UNIQUE; INFORMANT DISCREPANCIES; CHILD; PERCEPTIONS; PSYCHOPATHOLOGY; VALIDITY; MOTHERS; SCORES AB Parental rejection is linked to deep and enduring adjustment problems during adolescence. This study aims to further clarify this relation by demonstrating what has long been posited by parental acceptance/rejection theory but never validated empirically-namely that adolescents' unique or subjective experience of parental rejection independently informs their future adjustment. Among a longitudinal, multi-informant sample of 161 families (early adolescents were 47 % female and 40 % European American) this study utilized a multitrait-multimethod confirmatory factor analysis to isolate for each early adolescent-parent dyad, the adolescent's distinct view of parental rejection (i.e., the adolescent unique perspective) from the portion of his or her view that overlaps with his or her parent's view. The findings indicated that adolescents' unique perspectives of maternal rejection were not differentiated from their unique perspectives of paternal rejection. Also, consistent with parental acceptance-rejection theory, early adolescents' unique perspectives of parental rejection were associated with worse adjustment (internalizing and externalizing) 1 year later. This study further demonstrates the utility and validity of the multitrait-multimethod confirmatory factor analysis approach for identifying and examining adolescent unique perspectives. Both conceptually and analytically, this study also integrates research focused on unique perspectives with a distinct but related line of research focused on discrepancies in perspectives. C1 [Jager, Justin; An, Danming] Arizona State Univ, T Denny Sanford Sch Social & Family Dynam, POB 873701, Tempe, AZ 85287 USA. [Mahler, Alissa] Univ Calif Irvine, Dept Psychol & Social Behav, 5300 Social & Behav Sci Gateway, Irvine, CA 92697 USA. [Putnick, Diane L.; Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Child & Family Res, 6705 Rockledge Dr, Bethesda, MD 20892 USA. [Lansford, Jennifer E.; Dodge, Kenneth A.; Skinner, Ann T.] Duke Univ, Ctr Child & Family Policy, Box 90545, Durham, NC 27708 USA. [Deater-Deckard, Kirby] Univ Massachusetts, Dept Psychol & Brain Sci, 441 Tobin Hall, Amherst, MA 01003 USA. RP Jager, J (reprint author), Arizona State Univ, T Denny Sanford Sch Social & Family Dynam, POB 873701, Tempe, AZ 85287 USA. EM justin.jager@asu.edu; amahler@uci.edu; danming.an@asu.edu; putnickd@mail.nih.gov; Marc_H_Bornstein@nih.gov; lansford@duke.edu; dodge@duke.edu; askinner@duke.edu; kdeaterdeck@umass.edu OI Putnick, Diane/0000-0002-6323-749X FU Intramural Research Program of the NIH, NICHD; Eunice Kennedy Shriver National Institute of Child Health and Human Development [RO1-HD054805] FX DP and MB were supported by the Intramural Research Program of the NIH, NICHD. This research has been funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development grant RO1-HD054805. NR 34 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0047-2891 EI 1573-6601 J9 J YOUTH ADOLESCENCE JI J. Youth Adolesc. PD OCT PY 2016 VL 45 IS 10 SI SI BP 2108 EP 2124 DI 10.1007/s10964-016-0509-z PG 17 WC Psychology, Developmental SC Psychology GA DX7KX UT WOS:000384567200011 PM 27262697 ER PT J AU Johnson, SL Reichenberg, R Bradshaw, CP Haynie, DL Cheng, TL AF Johnson, Sarah Lindstrom Reichenberg, Raymond Bradshaw, Catherine P. Haynie, Denise L. Cheng, Tina L. TI Caregiver and Adolescent Discrepancies in Perceptions of Violence and Their Associations with Early Adolescent Aggression SO JOURNAL OF YOUTH AND ADOLESCENCE LA English DT Article DE Violence; Parents; Discrepancies; Structural equation modeling ID MIDDLE SCHOOL STUDENTS; COMMUNITY VIOLENCE; PSYCHOLOGICAL SYMPTOMS; COLLECTIVE EFFICACY; PARENTS KNOW; EXPOSURE; CHILDREN; YOUTH; BEHAVIORS; SUPPORT AB This article examined the role of caregiver messages about violence and exposure to neighborhood violence on adolescent aggression in light of research regarding discrepancies between parents and their children. Drawing upon data from an urban African American sample of 144 caregiver/early adolescent dyads (M = 12.99; SD = 0.93; 58.7 % female) we examined covariates of discrepancies between caregiver and adolescent reports of perceptions of violence as well as their association with adolescent aggression. Analyses suggested that concordance in perceptions of violence was associated with children's attitudes about violence and caregivers' perceptions of family communication. Structural equation modeling indicated a unique role for individual perceptions and suggested that agreement in awareness of neighborhood violence could be protective for early adolescent involvement in aggression. C1 [Johnson, Sarah Lindstrom; Reichenberg, Raymond] Arizona State Univ, POB 873701, Tempe, AZ 85287 USA. [Bradshaw, Catherine P.] Univ Virginia, Bavaro Hall,112D, Charlottesville, VA 22904 USA. [Haynie, Denise L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, 6100 Execut Blvd,Room 7B13P,MSC7510, Rockville, MD 20892 USA. [Cheng, Tina L.] Johns Hopkins Univ, 200 North Wolfe St,Suite 2055, Baltimore, MD 21287 USA. RP Johnson, SL (reprint author), Arizona State Univ, POB 873701, Tempe, AZ 85287 USA. EM sarahlj@asu.edu OI Haynie, Denise/0000-0002-8270-6079 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [1K24HD052559]; NICHD Intramural Research Program; DC-Baltimore Research Center on Child Health Disparities from the National Center on Minority Health and Health Disparities [P20 MD000198]; Centers for Disease Control and Prevention [U01CE0011954] FX This publication was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Grant Number 1K24HD052559 (Cheng) and the NICHD Intramural Research Program (Haynie), DC-Baltimore Research Center on Child Health Disparities Grant Number P20 MD000198 from the National Center on Minority Health and Health Disparities (Cheng), and Centers for Disease Control and Prevention Grant Number U01CE0011954 (Bradshaw). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the funding agencies. NR 45 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0047-2891 EI 1573-6601 J9 J YOUTH ADOLESCENCE JI J. Youth Adolesc. PD OCT PY 2016 VL 45 IS 10 SI SI BP 2125 EP 2137 DI 10.1007/s10964-016-0505-3 PG 13 WC Psychology, Developmental SC Psychology GA DX7KX UT WOS:000384567200012 ER PT J AU Ambikapathi, R Kosek, MN Lee, GO Mahopo, C Patil, CL Maciel, BL Turab, A Islam, MM Ulak, M Bose, A Olortegui, MP Pendergast, LL Murray-Kolb, LE Lang, D McCormick, BJJ Caulfield, LE AF Ambikapathi, Ramya Kosek, Margaret N. Lee, Gwenyth O. Mahopo, Cloupas Patil, Crystal L. Maciel, Bruna L. Turab, Ali Islam, M. Munirul Ulak, Manjeswori Bose, Anuradha Paredes Olortegui, Maribel Pendergast, Laura L. Murray-Kolb, Laura E. Lang, Dennis McCormick, Benjamin J. J. Caulfield, Laura E. TI How multiple episodes of exclusive breastfeeding impact estimates of exclusive breastfeeding duration: report from the eight-site MAL-ED birth cohort study SO MATERNAL AND CHILD NUTRITION LA English DT Article DE exclusive breastfeeding; duration; DHS; prevalence; metrics; MAL-ED; Nepal; Bangladesh; Pakistan; India; Brazil; Peru; Tanzania; South Africa ID INFANTS; HEALTH; SITE; CONSEQUENCES; PREVALENCE; BANGLADESH; BARRIERS; MOTHERS; EXAMPLE; AFRICA AB The duration of exclusive breastfeeding (EBF) is often defined as the time from birth to the first non-breast milk food/liquid fed (EBFLONG), or it is estimated by calculating the proportion of women at a given infant age who EBF in the previous 24h (EBFDHS). Others have measured the total days or personal prevalence of EBF (EBFPREV), recognizing that although non-EBF days may occur, EBF can be re-initiated for extended periods. We compared breastfeeding metrics in the MAL-ED study; infants' breastfeeding trajectories were characterized from enrollment (median 7days, IQR: 4, 12) to 180days at eight sites. During twice-weekly surveillance, caretakers were queried about infant feeding the prior day. Overall, 101833 visits and 356764 child days of data were collected from 1957 infants. Median duration of EBFLONG was 33days (95% CI: 32-36), compared to 49days based on the EBFDHS. Median EBFPREV was 66days (95% CI: 62-70). Differences were because of the return to EBF after a non-EBF period. The median number of returns to EBF was 2 (IQR: 1, 3). When mothers re-initiated EBF (second episode), infants gained an additional 18.8days (SD: 25.1) of EBF, and gained 13.7days (SD: 18.1) (third episode). In settings where women report short gaps in EBF, programmes should work with women to return to EBF. Interventions could positively influence the duration of these additional periods of EBF and their quantification should be considered in impact evaluation studies. (c) 2016 John Wiley & Sons Ltd C1 [Ambikapathi, Ramya; Murray-Kolb, Laura E.; Lang, Dennis; McCormick, Benjamin J. J.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. [Ambikapathi, Ramya; Kosek, Margaret N.; Lee, Gwenyth O.; Murray-Kolb, Laura E.; Caulfield, Laura E.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Ctr Human Nutr, 615 North Wolfe St,W2041, Baltimore, MD 21205 USA. [Mahopo, Cloupas] Univ Venda, Sch Hlth Sci, Dept Nutr, Thohoyandou, Limpopo Provinc, South Africa. [Patil, Crystal L.] Univ Illinois, Coll Nursing, Dept Women Children & Family Hlth Sci, Chicago, IL USA. [Maciel, Bruna L.] Univ Estadual Ceara, Dept Nutr, Fortaleza, Ceara, Brazil. [Turab, Ali; Pendergast, Laura L.] Aga Khan Univ, Dept Paediat & Child Hlth, Karachi, Pakistan. [Islam, M. Munirul] Int Ctr Diarrhoeal Dis Res, Ctr Nutr & Food Secur, Dhaka, Bangladesh. [Ulak, Manjeswori] Tribhuvan Univ, Dept Child Hlth, Kathmandu, Nepal. [Ulak, Manjeswori] Tribhuvan Univ, Inst Med, Kathmandu, Nepal. [Bose, Anuradha] Christian Med Coll & Hosp, Vellore, Tamil Nadu, India. [Paredes Olortegui, Maribel] Biomed Invest Unit AB PRISMA, Iquitos, Peru. Temple Univ, Sch Psychol Program, Philadelphia, PA 19122 USA. Penn State Univ, Dept Nutr Sci, State Coll, PA USA. RP Caulfield, LE (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Ctr Human Nutr, 615 North Wolfe St,W2041, Baltimore, MD 21205 USA. EM lcaulfi1@jhu.edu FU Bill & Melinda Gates Foundation; Foundation for the NIH; National Institutes of Health/Fogarty International Center; Integrative Graduate Education and Research Traineeship (IGERT) [1069213]; JHU Environment, Energy, Sustainability and Health Institute (E2SHI) fellowship; JHSPH Center of Global Health FX The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED) is carried out as a collaborative project supported by the Bill & Melinda Gates Foundation, the Foundation for the NIH and the National Institutes of Health/Fogarty International Center. Ramya Ambikapathi received the Kruse Family Publications Award and is funded by the Integrative Graduate Education and Research Traineeship (IGERT Award 1069213), a JHU Environment, Energy, Sustainability and Health Institute (E2SHI) fellowship and JHSPH Center of Global Health. NR 55 TC 1 Z9 1 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1740-8695 EI 1740-8709 J9 MATERN CHILD NUTR JI Matern. Child Nutr. PD OCT PY 2016 VL 12 IS 4 BP 740 EP 756 DI 10.1111/mcn.12352 PG 17 WC Nutrition & Dietetics; Pediatrics SC Nutrition & Dietetics; Pediatrics GA DX8QA UT WOS:000384652400008 PM 27500709 ER PT J AU Delitala, AP Steri, M Pilia, MG Dei, M Lai, S Delitala, G Schlessinger, D Cucca, F AF Delitala, Alessandro P. Steri, Maristella Pilia, Maria Grazia Dei, Mariano Lai, Sandra Delitala, Giuseppe Schlessinger, David Cucca, Francesco TI Menopause modulates the association between thyrotropin levels and lipid parameters: The SardiNIA study SO MATURITAS LA English DT Article DE Cholesterol; Subclinical hypothyroidism; TSH; Menopause; Estrogen ID DENSITY-LIPOPROTEIN CHOLESTEROL; THYROID-STIMULATING HORMONE; SUBCLINICAL HYPOTHYROIDISM; ARTERIAL STIFFNESS; HEPATIC LIPASE; DISEASE; TSH; AGE; POPULATION; PREVALENCE AB Objective: Thyroid hormone influences lipoprotein metabolism. The role of menopausal status in this association has not been extensively studied. The aim of the present study is to evaluate the association between lipid parameters and mild elevations of thyrotropin (TSH), and whether menopause influences this relationship. Study design: A cross-sectional study was conducted with a sample of 2,914 women (aged 14-102 years) from the SardiNIA study. Main outcome measures: The association of TSH with blood lipid levels was examined using regression analyses, according to menopausal status. Results: Postmenopausal women had lower serum TSH concentrations and higher levels of total cholesterol, low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), and triglycerides than did premenopausal women (p = 0.001 or less for all). In premenopausal women, after adjusting for the confounders age, BMI, smoking, insulin and glycaemia, TSH showed a direct relation to the levels of total cholesterol (beta = 0.046, p = 0.010), LDLc (beta = 0.044, p = 0.016) and triglycerides (beta = 0.085, p < 0.001), but no association with HDLc level. In the postmenopausal group, TSH was directly associated only with triglyceride levels (beta = 0.103, p = 0.014). Conclusions: The association between mild elevation of TSH and lipid levels is influenced by menopausal status. Further research is needed to clarify this finding. (C) 2016 Elsevier Ireland Ltd. All rights reserved. C1 [Delitala, Alessandro P.] Azienda Osped Univ Sassari, Viale San Pietro 8, I-07100 Sassari, Italy. [Steri, Maristella; Pilia, Maria Grazia; Dei, Mariano; Lai, Sandra; Cucca, Francesco] CNR, IRGB, Cittadella Univ Monserrato, Cagliari, Italy. [Delitala, Giuseppe] Univ Sassari, Dept Clin & Expt Med, Sassari, Italy. [Schlessinger, David] NIA, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [Cucca, Francesco] Univ Sassari, Dept Biomed Sci, Sassari, Italy. RP Delitala, AP (reprint author), Azienda Osped Univ Sassari, Viale San Pietro 8, I-07100 Sassari, Italy. EM aledelitala@tiscali.it FU NIH, National Institute on Aging [NO1-AG-1-2109] FX This work was supported in part by Contract NO1-AG-1-2109 from the NIH, National Institute on Aging. NR 31 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-5122 EI 1873-4111 J9 MATURITAS JI Maturitas PD OCT PY 2016 VL 92 BP 30 EP 34 DI 10.1016/j.maturitas.2016.07.003 PG 5 WC Geriatrics & Gerontology; Obstetrics & Gynecology SC Geriatrics & Gerontology; Obstetrics & Gynecology GA DY0LG UT WOS:000384787700006 PM 27621235 ER PT J AU Brosh, RM AF Brosh, Robert M. Jrr TI Special Methods collection on DNA helicases SO METHODS LA English DT Editorial Material AB In this special Methods collection on DNA helicases, I have solicited articles from leading experts in the field with a priority to gather a defined series of papers on highly relevant topics that encompass biological, biochemical, and biophysical aspects of helicase function. The experimental approaches described provide an opportunity for both new and more experienced scientists to use the information for the design of their own investigations. The reader will find detailed methods for single -molecule studies, novel biochemical experiments, genetic analyses, and cell biological assays in a variety of systems with an emphasis placed on state-of-the-art techniques to measure helicase function. Contributing authors were strongly encouraged to provide a carefully constructed description of the methods employed so that others might use this information in a manner that will be useful for their own particular application and helicase of interest. This special issue of Methods dedicated to DNA helicases offers readers a treasure chest of unique experimental approaches and protocols focused on rapidly developing techniques that are useful for studying both in vivo and in vitro aspects of helicase function. Published by Elsevier Inc. C1 [Brosh, Robert M. Jrr] NIA, Lab Mol Gerontol, NIH, NIH Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, NIH Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM broshr@mail.nih.gov NR 16 TC 0 Z9 0 U1 3 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 EI 1095-9130 J9 METHODS JI Methods PD OCT 1 PY 2016 VL 108 BP 1 EP 3 DI 10.1016/j.ymeth.2016.08.009 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DX8IY UT WOS:000384632500001 PM 27565743 ER PT J AU Lu, X Parvathaneni, S Li, XL Lal, A Sharma, S AF Lu, Xing Parvathaneni, Swetha Li, Xiao Ling Lal, Ashish Sharma, Sudha TI Transcriptome guided identification of novel functions of RECQ1 helicase SO METHODS LA English DT Article DE Gene expression; RecQ; Helicase; G4; Cell migration; Cell invasion ID G-QUADRUPLEX DNA; REPLICATION STRESS; GENE-EXPRESSION; CANCER; ROLES; RESISTANCE; PROMOTERS; GENOME; REPAIR; DAMAGE AB Gene expression changes in the functional absence of a specific RecQ protein, and how that relates to disease outcomes including cancer predisposition and premature aging in RecQ helicase associated syndromes, are poorly understood. Here we describe detailed experimental strategy for identification of RECQ1-regulated transcriptome that led us to uncover a novel association of RECQ1 in regulation of cancer cell migration and invasion. We initiated a focused study to determine whether RECQ1, the most abundant RecQ protein in humans, alters gene expression and also investigated whether RECQ1 binds with G4 motifs predicted to form G-quadruplex structures in the target gene promoters. Rescue of mRNA expression of select RECQ1-downregulated genes harboring G4 motifs required wild-type RECQ1 helicase. However, some RECQ1-regulated genes are also regulated by BLM and WRN proteins regardless of the presence or absence of G4 motifs. The approach described here is applicable for systematic comparison of gene expression signatures of individual RecQ proteins in isogenic background, and to elucidate their participation in transcription regulation through G-quadruplex recognition and/or resolution. Such strategies might also reveal molecular pathways that drive the pathogenesis of cancer and other diseases in specific RecQ deficiency. (C) 2016 Elsevier Inc. All rights reserved. C1 [Lu, Xing; Parvathaneni, Swetha; Sharma, Sudha] Howard Univ, Dept Biochem & Mol Biol, Coll Med, 520 W St NW, Washington, DC 20059 USA. [Li, Xiao Ling; Lal, Ashish] NCI, Regulatory RNAs & Canc Sect, Genet Branch, NIH, Bethesda, MD 20892 USA. RP Sharma, S (reprint author), Howard Univ, Dept Biochem & Mol Biol, Coll Med, 520 W St NW, Washington, DC 20059 USA. EM sudha.sharma@howard.edu OI Sharma, Sudha/0000-0003-2765-2482 FU NIGMS/NIH [5SC1GM093999-06]; Intramural Research Program of the National Institutes of Health, National Cancer Institute, and Center for Cancer Research; NIMHD/NIH [G12MD007597] FX This work was funded by the NIGMS/NIH Grant 5SC1GM093999-06 to Sudha Sharma and the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and Center for Cancer Research to Ashish Lal. We also acknowledge infrastructure support from the NIMHD/NIH under award number G12MD007597. NR 36 TC 2 Z9 2 U1 2 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 EI 1095-9130 J9 METHODS JI Methods PD OCT 1 PY 2016 VL 108 BP 111 EP 117 DI 10.1016/j.ymeth.2016.04.018 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DX8IY UT WOS:000384632500012 PM 27102625 ER PT J AU Banerjee, T Aggarwal, M Sommers, JA Brosh, RM AF Banerjee, Taraswi Aggarwal, Monika Sommers, Joshua A. Brosh, Robert M., Jr. TI Biochemical and cell biological assays to identify and characterize DNA helicase inhibitors SO METHODS LA English DT Article DE Helicase; Replication; DNA repair; Small molecule; Inhibitor; Werner syndrome; Cancer therapy ID WERNER-SYNDROME HELICASE; FANCONI-ANEMIA PATHWAY; HOMOLOGOUS RECOMBINATION; SYNTHETIC LETHALITY; RECENT PROGRESS; CANCER-THERAPY; REPAIR; TELOMERES; BINDING; DISSOCIATION AB The growing number of DNA helicases implicated in hereditary disorders and cancer indicates that this particular class of enzymes plays key roles in genomic stability and cellular homeostasis. Indeed, a large body of work has provided molecular and cellular evidence that helicases act upon a variety of nucleic acid substrates and interact with numerous proteins to enact their functions in replication, DNA repair, recombination, and transcription. Understanding how helicases operate in unique and overlapping pathways is a great challenge to researchers. In this review, we describe a series of experimental approaches and methodologies to identify and characterize DNA helicase inhibitors which collectively provide an alternative and useful strategy to explore their biological significance in cell-based systems. These procedures were used in the discovery of biologically active compounds that inhibited the DNA unwinding function catalyzed by the human WRN helicase-nuclease defective in the premature aging disorder Werner syndrome. We describe in vitro and in vivo experimental approaches to characterize helicase inhibitors with WRN as the model, anticipating that these approaches may be extrapolated to other DNA helicases, particularly those implicated in DNA repair and/or the replication stress response. Published by Elsevier Inc. C1 [Banerjee, Taraswi; Sommers, Joshua A.; Brosh, Robert M., Jr.] NIA, Lab Mol Gerontol, NIH, NIH Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. [Aggarwal, Monika] Georgetown Univ, Lombardi Comprehens Canc Res Ctr, Med Ctr, Washington, DC 20057 USA. RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, NIH Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM broshr@mail.nih.gov FU Intramural Research Program of the NIH, National Institute on Aging FX This research was supported in full by the Intramural Research Program of the NIH, National Institute on Aging. NR 39 TC 2 Z9 2 U1 8 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 EI 1095-9130 J9 METHODS JI Methods PD OCT 1 PY 2016 VL 108 BP 130 EP 141 DI 10.1016/j.ymeth.2016.04.007 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DX8IY UT WOS:000384632500014 PM 27064001 ER PT J AU Denkert, C Wienert, S Poterie, A Loibl, S Budczies, J Badve, S Bago-Horvath, Z Bane, A Bedri, S Brock, J Chmielik, E Christgen, M Colpaert, C Demaria, S Van den Eynden, G Floris, G Fox, SB Gao, D Heppner, BI Kim, SR Kos, Z Kreipe, HH Lakhani, SR Penault-Llorca, F Pruneri, G Radosevic-Robin, N Rimm, DL Schnitt, SJ Sinn, BV Sinn, P Sirtaine, N O'Toole, SA Viale, G Van de Vijver, K de Wind, R von Minckwitz, G Klauschen, F Untch, M Fasching, PA Reimer, T Willard-Gallo, K Michiels, S Loi, S Salgado, R AF Denkert, Carsten Wienert, Stephan Poterie, Audrey Loibl, Sibylle Budczies, Jan Badve, Sunil Bago-Horvath, Zsuzsanna Bane, Anita Bedri, Shahinaz Brock, Jane Chmielik, Ewa Christgen, Matthias Colpaert, Cecile Demaria, Sandra Van den Eynden, Gert Floris, Giuseppe Fox, Stephen B. Gao, Dongxia Heppner, Barbara Ingold Kim, S. Rim Kos, Zuzana Kreipe, Hans H. Lakhani, Sunil R. Penault-Llorca, Frederique Pruneri, Giancarlo Radosevic-Robin, Nina Rimm, David L. Schnitt, Stuart J. Sinn, Bruno V. Sinn, Peter Sirtaine, Nicolas O'Toole, Sandra A. Viale, Giuseppe Van de Vijver, Koen de Wind, Roland von Minckwitz, Gunter Klauschen, Frederick Untch, Michael Fasching, Peter A. Reimer, Toralf Willard-Gallo, Karen Michiels, Stefan Loi, Sherene Salgado, Roberto TI Standardized evaluation of tumor-infiltrating lymphocytes in breast cancer: results of the ring studies of the international immuno-oncology biomarker working group SO MODERN PATHOLOGY LA English DT Article ID NEOADJUVANT CHEMOTHERAPY; CARBOPLATIN; TRIALS AB Multiple independent studies have shown that tumor-infiltrating lymphocytes (TIL) are prognostic in breast cancer with potential relevance for response to immune-checkpoint inhibitor therapy. Although many groups are currently evaluating TIL, there is no standardized system for diagnostic applications. This study reports the results of two ring studies investigating TIL conducted by the International Working Group on Immuno-oncology Biomarkers. The study aim was to determine the intraclass correlation coefficient (ICC) for evaluation of TIL by different pathologists. A total of 120 slides were evaluated by a large group of pathologists with a web-based system in ring study 1 and a more advanced software-system in ring study 2 that included an integrated feedback with standardized reference images. The predefined aim for successful ring studies 1 and 2 was an ICC above 0.7 (lower limit of 95% confidence interval (CI)). In ring study 1 the prespecified endpoint was not reached (ICC: 0.70; 95% CI: 0.62-0.78). On the basis of an analysis of sources of variation, we developed a more advanced digital image evaluation system for ring study 2, which improved the ICC to 0.89 (95% CI: 0.85-0.92). The Fleiss' kappa value for o60 vs >= 60% TIL improved from 0.45 (ring study 1) to 0.63 in RS2 and the mean concordance improved from 88 to 92%. This large international standardization project shows that reproducible evaluation of TIL is feasible in breast cancer. This opens the way for standardized reporting of tumor immunological parameters in clinical studies and diagnostic practice. The software-guided image evaluation approach used in ring study 2 may be of value as a tool for evaluation of TIL in clinical trials and diagnostic practice. The experience gained from this approach might be applicable to the standardization of other diagnostic parameters in histopathology. C1 [Denkert, Carsten; Wienert, Stephan; Budczies, Jan; Heppner, Barbara Ingold; Sinn, Bruno V.; Klauschen, Frederick] Charite, Inst Pathol, Charitepl 1, D-10117 Berlin, Germany. [Denkert, Carsten; Budczies, Jan] German Canc Consortium DKTK, Partner Site Berlin, Berlin, Germany. [Wienert, Stephan] VMscope GmbH, Berlin, Germany. [Poterie, Audrey] Inst Gustave Roussy, Serv Biostat & Epidemiol, Villejuif, France. [Loibl, Sibylle; von Minckwitz, Gunter] GBG, Neu Isenburg, Germany. [Loibl, Sibylle] Sana Klinikum Offenbach, Clin Gynecol & Obstet, Offenbach, Germany. [Badve, Sunil] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Bago-Horvath, Zsuzsanna] Med Univ Wien, Clin Inst Pathol, Vienna, Austria. [Bane, Anita] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada. [Bedri, Shahinaz] Weill Cornell Med Coll, Doha, Qatar. [Brock, Jane] Harvard Med Sch, Boston, MA USA. [Chmielik, Ewa] Maria Sklodowska Curie Mem Canc Ctr, Tumor Pathol Dept, Gliwice, Poland. [Chmielik, Ewa] Inst Oncol, Gliwice Branch, Gliwice, Poland. [Christgen, Matthias; Kreipe, Hans H.] Hannover Med Sch, Inst Pathol, Hannover, Germany. [Colpaert, Cecile] Sint Augustinus, GZA Ziekenhuizen, Pathol, Antwerp, Belgium. [Demaria, Sandra] Weill Cornell Med Coll, Radiat Oncol & Pathol, New York, NY USA. [Van den Eynden, Gert; Salgado, Roberto] GZA Hosp, Dept Pathol & Cytol, Antwerp, Belgium. [Floris, Giuseppe] Univ Hosp Leuven, Dept Pathol, Leuven, Belgium. [Fox, Stephen B.] Peter MacCallum Canc Ctr, Dept Pathol, Melbourne, Vic, Australia. [Gao, Dongxia] Vancouver Hosp, Anat Pathol, Vancouver, BC, Canada. [Kim, S. Rim] NSABP, Div Pathol, Pittsburgh, PA USA. [Kos, Zuzana] Univ Ottawa, Dept Pathol & Lab Med, Ottawa, ON, Canada. [Lakhani, Sunil R.] Univ Queensland, Clin Res Ctr, UQ Sch Med & Pathol Queensland, Brisbane, Qld, Australia. [Penault-Llorca, Frederique; Radosevic-Robin, Nina] Univ Auvergne, Jean Perrin Comprehens Canc Ctr, Dept Pathol, ERTICa Res Team, EA4677, Clermont Ferrand, France. [Pruneri, Giancarlo] Univ Milan, Div Pathol & Lab Med, Milan, Italy. [Rimm, David L.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. [Schnitt, Stuart J.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Sinn, Bruno V.] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA. [Sinn, Peter] Heidelberg Univ, Inst Pathol, Sekt Gynakopathol, Heidelberg, Germany. [Sirtaine, Nicolas] Inst Jules Bordet, Anat Pathol, Brussels, Belgium. [O'Toole, Sandra A.] Royal Prince Alfred Hosp, Dept Tissue Pathol & Diagnost Oncol, Mol Diagnost Oncol, Camperdown, NSW, Australia. [Viale, Giuseppe] Univ Milan, European Inst Oncol, Dept Pathol, Milan, Italy. [Van de Vijver, Koen] Netherlands Canc Inst, Dept Pathol, Amsterdam, Netherlands. [de Wind, Roland] Inst Jules Bordet, Brussels, Belgium. [Untch, Michael] Helios Klinikum Berlin Buch, Dept Gynecol, Berlin, Germany. [Fasching, Peter A.] Univ Erlangen Nurnberg, Comprehens Canc Ctr Erlangen EMN, Univ Hosp Erlangen, Dept Gynecol & Obstet, Erlangen, Germany. [Reimer, Toralf] Klinikum Sudstadt Rostock, Dept Gynecol, Rostock, Germany. [Willard-Gallo, Karen] Inst Jules Bordet, Mol Immunol Unit, Brussels, Belgium. [Michiels, Stefan] Univ Paris Saclay, Univ Paris 11, Serv Biostat & Epidemiol, Gustave Roussy,CESP,Inserm U1018, Villejuif, France. [Loi, Sherene] Peter MacCallum Canc Ctr, Div Res & Clin Med, Melbourne, Vic, Australia. [Salgado, Roberto] Inst Jules Bordet, Breast Canc Translat Res Lab, Brussels, Belgium. RP Denkert, C (reprint author), Charite, Inst Pathol, Charitepl 1, D-10117 Berlin, Germany. EM carsten.denkert@charite.de RI Michiels, Stefan/L-1516-2013; OI Michiels, Stefan/0000-0002-6963-2968; Fox, Stephen/0000-0002-7648-8896 FU European Commission [278659, BMBF-01KT1314] FX We would like to thank all patients, clinicians, and pathologists participating in the clinical studies and the biomaterial collection. We are grateful for the excellent technical assistance by Britta Beyer, Sylwia Handzik, Ines Koch, Petra Wachs as well as Peggy Wolkenstein. Funding was given by the European Commission FP7, Grant 278659 (RESPONSIFY) and the TRANSCAN-I, Grant BMBF-01KT1314 (TRANSCAN-I UGI 1). NR 20 TC 6 Z9 6 U1 6 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD OCT PY 2016 VL 29 IS 10 BP 1155 EP 1164 DI 10.1038/modpathol.2016.109 PG 10 WC Pathology SC Pathology GA DX7DZ UT WOS:000384548100003 PM 27363491 ER PT J AU Alikhan, M Song, JY Sohani, AR Moroch, J Plonquet, A Duffield, AS Borowitz, MJ Jiang, LY Bueso-Ramos, C Inamdar, K Menon, MP Gurbuxani, S Chan, E Smith, SM Nicolae, A Jaffe, ES Gaulard, P Venkataraman, G AF Alikhan, Mir Song, Joo Y. Sohani, Aliyah R. Moroch, Julien Plonquet, Anne Duffield, Amy S. Borowitz, Michael J. Jiang, Liuyan Bueso-Ramos, Carlos Inamdar, Kedar Menon, Madhu P. Gurbuxani, Sandeep Chan, Ernest Smith, Sonali M. Nicolae, Alina Jaffe, Elaine S. Gaulard, Philippe Venkataraman, Girish TI Peripheral T-cell lymphomas of follicular helper T-cell type frequently display an aberrant CD3(-/dim)CD(4+) population by flow cytometry: an important clue to the diagnosis of a Hodgkin lymphoma mimic SO MODERN PATHOLOGY LA English DT Article ID IMMUNOPHENOTYPIC ANALYSIS; CONSENSUS RECOMMENDATIONS; NEOPLASTIC-CELLS; GROWTH-PATTERN; EXPRESSION; CD10; PHENOTYPE; INVOLVEMENT; PROGRESSION; DISEASE AB Nodal follicular helper T-cell-derived lymphoproliferations (specifically the less common peripheral T-cell lymphomas of follicular type) exhibit a spectrum of histologic features that may mimic reactive hyperplasia or Hodgkin lymphoma. Even though angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma of follicular type share a common biologic origin from follicular helper T-cells and their morphology has been well characterized, flow cytometry of peripheral T-cell lymphomas of follicular type has not been widely discussed as a tool for identifying this reactive hyperplasia/Hodgkin lymphoma mimic. We identified 10 peripheral T-cell lymphomas of follicular type with available flow cytometry data from five different institutions, including two cases with peripheral blood evaluation. For comparison, we examined flow cytometry data for 8 classical Hodgkin lymphomas (including 1 lymphocyte-rich classical Hodgkin lymphoma), 15 nodular lymphocyte predominant Hodgkin lymphomas, 15 angioimmunoblastic T-cell lymphomas, and 26 reactive nodes. Lymph node histology and flow cytometry data were reviewed, specifically for the presence of a CD3-/dimCD4+ aberrant T-cell population (described in angioimmunoblastic T-cell lymphomas), besides other T-cell aberrancies. Nine of 10 (90%) peripheral T-cell lymphomas of follicular type showed a CD3-/dimCD4+ T-cell population constituting 29.3% (range 7.9-62%) of all lymphocytes. Five of 10 (50%) had nodular lymphocyte predominant Hodgkin lymphoma or lymphocyte-rich classical Hodgkin lymphoma-like morphology with scattered Hodgkin-like cells that expressed CD20, CD30, CD15, and MUM1. Three cases had a nodular growth pattern and three others exhibited a perifollicular growth pattern without Hodgkin-like cells. Epstein-Barr virus was positive in 1 of 10 cases (10%). PCR analysis showed clonal T-cell receptor gamma gene rearrangement in all 10 peripheral T-cell lymphomas of follicular type. By flow cytometry, 11 of 15 (73.3%) angioimmunoblastic T-cell lymphomas showed the CD3-/dimCD4+ population (mean: 19.5%, range: 3-71.8%). Using a threshold of 3% for CD3-/dimCD4+ T cells, all 15 nodular lymphocyte predominant Hodgkin lymphoma controls and 8 classical Hodgkin lymphomas were negative (Mann-Whitney P = 0.01, F-PTCL vs Hodgkin lymphomas), as were 25 of 26 reactive lymph nodes. The high frequency of CD3-/dimCD4+ aberrant T cells is similar in angioimmunoblastic T-cell lymphomas and peripheral T-cell lymphomas of follicular type, and is a useful feature in distinguishing peripheral T-cell lymphomas of follicular type from morphologic mimics such as reactive hyperplasia or Hodgkin lymphoma. C1 [Alikhan, Mir; Gurbuxani, Sandeep; Chan, Ernest; Venkataraman, Girish] Univ Chicago, Dept Pathol, 5841 S Maryland Ave, Chicago, IL 60637 USA. [Song, Joo Y.] City Hope Natl Med Ctr, Med Ctr, Dept Pathol, Duarte, CA USA. [Sohani, Aliyah R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Moroch, Julien; Gaulard, Philippe] Univ Paris Est, Hop Henri Mondor, Dept Pathol, Creteil, France. [Plonquet, Anne] Univ Paris Est, Hop Henri Mondor, Dept Immunol, Creteil, France. [Duffield, Amy S.; Borowitz, Michael J.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [Jiang, Liuyan] Mayo Clin, Dept Pathol, Jacksonville, FL 32224 USA. [Bueso-Ramos, Carlos] MD Anderson Canc Ctr, Dept Pathol, Houston, TX USA. [Inamdar, Kedar; Menon, Madhu P.] Henry Ford Hlth Syst, Dept Pathol, Detroit, MI USA. [Smith, Sonali M.] Univ Chicago, Dept Hematol Oncol, Chicago, IL 60637 USA. [Nicolae, Alina; Jaffe, Elaine S.] NCI, Hematopathol Sect, NIH, Bethesda, MD 20892 USA. RP Venkataraman, G (reprint author), Univ Chicago, Dept Pathol, Hematopathol Sect, 5841S Maryland Ave,TW055,MC0008, Chicago, IL 60637 USA. EM Girish.Venkataraman@uchospitals.edu NR 31 TC 1 Z9 1 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD OCT PY 2016 VL 29 IS 10 BP 1173 EP 1182 DI 10.1038/modpathol.2016.113 PG 10 WC Pathology SC Pathology GA DX7DZ UT WOS:000384548100005 PM 27312067 ER PT J AU Han, JW Lee, YH Yoen, SI Abramowitz, J Birnbaumer, L Lee, MG Kim, JY AF Han, Jung Woo Lee, Young Ho Yoen, Su-In Abramowitz, Joel Birnbaumer, Lutz Lee, Min Goo Kim, Joo Young TI Resistance to pathologic cardiac hypertrophy and reduced expression of Ca(V)1.2 in Trpc3-depleted mice SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE Transient receptor potential canonical channels 3; L-type Ca2+ channel; Pathologic cardiac hypertrophy; Ca2+ influx ID RECEPTOR POTENTIAL CHANNELS; TRPC CHANNELS; CA2+ CHANNELS; VENTRICULAR DYSFUNCTION; PRESSURE-OVERLOAD; BLOOD-PRESSURE; HEART-FAILURE; MOUSE HEART; CALCINEURIN; INHIBITION AB Sustained elevation of intracellular Ca2+ concentration ([Ca2+](i)) reprograms cardiovascular cell fate, leading to cellular hypertrophy via Ca2+-calmodulin/calcineurin (Cn)/NFAT activation. Accumulating evidence suggests that transient receptor potential canonical (Trpc) channels play important roles in the development of pathologic cardiac hypertrophy. Here, we demonstrated that Trpc3 mediates pathologic cardiac hypertrophy in neurohumoral elevation via direct regulation of Ca(V)1.2 expressions. Elevated PE (phenylephrine) was maintained in mice by continuous infusion using an osmotic pump. Wild-type (WT) mice, but not Trpc3 (-/-) showed a sudden decrease in blood pressure (BP) or death following elevation of BP under conditions of elevated PE. Trpc3 (-/-) mesenteric artery showed decreased PE-stimulated vasoconstriction. Analysis of morphology, function, and pathologic marker expression revealed that PE elevation caused pathologic cardiac hypertrophy in WT mice, which was prevented by deletion of Trpc3. Interestingly, protection by Trpc3 deletion seemed to be a result of reduced cardiac Ca(V)1.2 expressions. Basal and PE induced increased expression of protein and mRNA of Ca(V)1.2 was decreased in Trpc3 (-/-) heart. Accordingly, altered expression of Ca(V)1.2 was observed by knockdown or stimulation of Trpc3 in cardiomyocytes. These findings suggest that Trpc3 is a mediator of pathologic cardiac hypertrophy not only through mediating part of the Ca2+ influx, but also through control of Ca(V)1.2 expressions. C1 [Han, Jung Woo; Lee, Min Goo; Kim, Joo Young] Yonsei Univ, Coll Med, PLUS Project Med Sci 21, Dept Pharmacol & Brain Korea, 50 Yonsei Ro, Seoul 120752, South Korea. [Lee, Young Ho; Yoen, Su-In] Yonsei Univ, Coll Med, Dept Physiol & Brain Korea, PLUS Project Med Sci 21, Seoul 120752, South Korea. [Abramowitz, Joel; Birnbaumer, Lutz] NIEHS, Neurobiol Lab, Durham, NC 27709 USA. RP Kim, JY (reprint author), Yonsei Univ, Coll Med, PLUS Project Med Sci 21, Dept Pharmacol & Brain Korea, 50 Yonsei Ro, Seoul 120752, South Korea. EM ad2011@naver.com; YHLEE@yuhs.ac; YSI2012@yuhs.ac; abramow1@niehs.nih.gov; birnbau1@gmail.com; mlee@yuhs.ac; jooyoungkim@yuhs.ac RI Abramowitz, Joel/A-2620-2015; Lee, Min Goo/D-5635-2012 OI Lee, Min Goo/0000-0001-7436-012X FU National Research Foundation of Korea (NRF) - Korean government [NRF-2011-0029459, MSIP-2013R1A3A2042197]; Intramural Research Program of the NIH [Z01-ES101864] FX We thank Jeungsik In in CPEC (Cardiovascular Product Evaluation Center) at Yonsei University Health System, Jangwoo Cho in SI healthcare and Heinmiller, Andrew in VisualSonics Inc. for helping echocardiogram measurements and analysis. This work was supported by a National Research Foundation of Korea (NRF) Grant funded by the Korean government (No. NRF-2011-0029459 for JY KIM, MSIP-2013R1A3A2042197 for MG LEE) and the Intramural Research Program of the NIH (Project Z01-ES101864 to LB). NR 47 TC 0 Z9 0 U1 5 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 EI 1573-4919 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD OCT PY 2016 VL 421 IS 1-2 BP 55 EP 65 DI 10.1007/s11010-016-2784-0 PG 11 WC Cell Biology SC Cell Biology GA DW5EL UT WOS:000383665000005 PM 27522668 ER PT J AU Gautam, A Kumar, R Dimitrov, G Hoke, A Hammamieh, R Jett, M AF Gautam, Aarti Kumar, Raina Dimitrov, George Hoke, Allison Hammamieh, Rasha Jett, Marti TI Identification of extracellular miRNA in archived serum samples by next-generation sequencing from RNA extracted using multiple methods SO MOLECULAR BIOLOGY REPORTS LA English DT Article DE DoDSR; miRNA; Next-generation sequencing; Serum; Data analysis ID CIRCULATING MICRORNA; BODY-FLUIDS; PLASMA; EXPRESSION; BIOMARKERS; MIRBASE; MICROARRAY; CANCER; BIOGENESIS; DIAGNOSIS AB miRNAs act as important regulators of gene expression by promoting mRNA degradation or by attenuating protein translation. Since miRNAs are stably expressed in bodily fluids, there is growing interest in profiling these miRNAs, as it is minimally invasive and cost-effective as a diagnostic matrix. A technical hurdle in studying miRNA dynamics is the ability to reliably extract miRNA as small sample volumes and low RNA abundance create challenges for extraction and downstream applications. The purpose of this study was to develop a pipeline for the recovery of miRNA using small volumes of archived serum samples. The RNA was extracted employing several widely utilized RNA isolation kits/methods with and without addition of a carrier. The small RNA library preparation was carried out using Illumina TruSeq small RNA kit and sequencing was carried out using Illumina platform. A fraction of five microliters of total RNA was used for library preparation as quantification is below the detection limit. We were able to profile miRNA levels in serum from all the methods tested. We found out that addition of nucleic acid based carrier molecules had higher numbers of processed reads but it did not enhance the mapping of any miRBase annotated sequences. However, some of the extraction procedures offer certain advantages: RNA extracted by TRIzol seemed to align to the miRBase best; extractions using TRIzol with carrier yielded higher miRNA-to-small RNA ratios. Nuclease free glycogen can be carrier of choice for miRNA sequencing. Our findings illustrate that miRNA extraction and quantification is influenced by the choice of methodologies. Addition of nucleic acid- based carrier molecules during extraction procedure is not a good choice when assaying miRNA using sequencing. The careful selection of an extraction method permits the archived serum samples to become valuable resources for high-throughput applications. C1 [Gautam, Aarti; Hammamieh, Rasha; Jett, Marti] US Army Ctr Environm Hlth Res, 568 Doughten Dr, Ft Detrick, MD 21702 USA. [Kumar, Raina; Dimitrov, George] Leidos Biomed Inc, Adv Biomed Comp Ctr, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Hoke, Allison] US Army Ctr Environm Hlth Res, Geneva Fdn, Ft Detrick, MD 21702 USA. RP Jett, M (reprint author), US Army Ctr Environm Hlth Res, 568 Doughten Dr, Ft Detrick, MD 21702 USA. EM marti.jett-tilton.civ@mail.mil FU Military Operational Medicine Research Program at the United States Army Medical Research and Materiel Command (USAMRMC) at Fort Detrick, MD FX Work was supported by funding from the Military Operational Medicine Research Program at the United States Army Medical Research and Materiel Command (USAMRMC) at Fort Detrick, MD, in preparation for carrying out a clinical trial of longitudinal assessment with Dr. Charles Marmar, New York University Medical Center. Volunteers separately consented for approval to use their archived samples in conjunction with their current participation in the study. The data presented herein was obtained using "test samples" from the DoDSR in preparation for the overarching study. We would like to thank Dr. Julia Scheerer for her input. NR 66 TC 0 Z9 0 U1 7 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0301-4851 EI 1573-4978 J9 MOL BIOL REP JI Mol. Biol. Rep. PD OCT PY 2016 VL 43 IS 10 BP 1165 EP 1178 DI 10.1007/s11033-016-4043-6 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA DW3ZW UT WOS:000383582600015 PM 27510798 ER PT J AU Shridhar, K Aggarwal, A Walia, GK Gulati, S Geetha, AV Prabhakaran, D Dhillon, PK Rajaraman, P AF Shridhar, Krithiga Aggarwal, Aastha Walia, Gagandeep Kaur Gulati, Smriti Geetha, A. V. Prabhakaran, D. Dhillon, Preet K. Rajaraman, Preetha TI Single nucleotide polymorphisms as markers of genetic susceptibility for oral potentially malignant disorders risk: Review of evidence to date SO ORAL ONCOLOGY LA English DT Review DE Oral potentially malignant disorders; Susceptibility; SNP; Polymorphisms ID SQUAMOUS-CELL CARCINOMA; GENOME-WIDE ASSOCIATION; NORTH INDIAN POPULATION; NECROSIS-FACTOR-ALPHA; BETEL QUID CHEWERS; SUBMUCOUS FIBROSIS; PREMALIGNANT LESIONS; DNA-REPAIR; CANCER-RISK; FUNCTIONAL POLYMORPHISM AB Background: Oral cancers are preceded by oral potentially malignant disorders (OPMD). Understanding genetic susceptibility for OPMD risk could provide an opportunity for risk assessment of oral cancer through early disease course. We conducted a review of single nucleotide polymorphism (SNP) studies for OPMD risk. Methods: We identified all relevant studies examining associations of SNPs with OPMD (leukoplakia, erythroplakia and oral sub-mucous fibrosis) conducted world-wide between January, 2000 and February, 2016 using a combined keyword search on PubMed. Of these, 47 studies that presented results as odds ratios and 95% CI were considered for full review. Results: The majority of eligible studies that explored candidate gene associations for OPMD were small (N < 200 cases), limiting their scope to provide strong inference for any SNP identified to date in any population. Commonly studied SNPs were genes of carcinogen metabolism (n = 18 studies), DNA repair (n = 11 studies), cell cycle control (n = 8 studies), extra-cellular matrix alteration (n = 8 studies) and immune-inflammatory (n = 6 studies) pathways. Based on significant associations as reported by two or more studies, suggestive markers included SNPs in GSTM1 (null), CCND1 (G870A), MMP3 (-1171; promotor region), TNF alpha (-308; rs800629), XPD (codon 751) and Gemin3 (rs197412) as well as in p53 (codon 72) in Indian populations. However, an equal or greater number of studies reported null or mixed associations for SNPs in GSTM1 (null), p53 (codon 72), XPD (codon 751), XRCC (rs25487 C/T), GSTT1 (null) and CYP1A1m1 (MspI site). Conclusion: Candidate gene association studies have not yielded consistent data on risk loci for OPMD. High-throughput genotyping approaches for OPMD, with concurrent efforts for oral cancer, could prove useful in identifying robust risk-loci to help understand early disease course susceptibility for oral cancer. (C) 2016 The Authors. Published by Elsevier Ltd. C1 [Shridhar, Krithiga; Aggarwal, Aastha; Walia, Gagandeep Kaur; Gulati, Smriti; Geetha, A. V.; Prabhakaran, D.; Dhillon, Preet K.] Publ Hlth Fdn India, Ctr Chron Condit & Injuries, 4th Floor,Plot 47,Sect 44, Gurgaon 122002, Haryana, India. [Prabhakaran, D.] Ctr Chron Dis Control, Gurgaon, Haryana, India. [Prabhakaran, D.] London Sch Hyg & Trop Med, London, England. [Rajaraman, Preetha] NCI, Ctr Global Hlth, Bethesda, MD 20892 USA. RP Shridhar, K (reprint author), Publ Hlth Fdn India, Ctr Chron Condit & Injuries, 4th Floor,Plot 47,Sect 44, Gurgaon 122002, Haryana, India. EM g.krithiga@phfi.org; aastha.aggrawal@phfi.org; gagandeep.k.walia@phfi.org; smriti5gulati@gmail.com; geetha.nambiar@phfi.org; dprabakaran@ccdcindia.org; preet.dhillon@phfi.org; rajarama@mail.nih.gov OI Prabhakaran, Dorairaj/0000-0002-3172-834X FU Wellcome Trust; consortium of UK universities [WT084754/Z/08/A] FX This work was supported by a Wellcome Trust Capacity Strengthening Strategic Award Extension phase to the Public Health Foundation of India and a consortium of UK universities (WT084754/Z/08/A). NR 68 TC 0 Z9 0 U1 6 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 EI 1879-0593 J9 ORAL ONCOL JI Oral Oncol. PD OCT PY 2016 VL 61 BP 146 EP 151 DI 10.1016/j.oraloncology.2016.08.005 PG 6 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA DX9EC UT WOS:000384695400022 PM 27688118 ER PT J AU Ernst, M Lago, T Davis, A Grillon, C AF Ernst, Monique Lago, Tiffany Davis, Andrew Grillon, Christian TI The effects of methylphenidate and propranolol on the interplay between induced-anxiety and working memory SO PSYCHOPHARMACOLOGY LA English DT Article DE Fear-potentiated startle; Stimulant; Cognition; Limited resources theory; Dopamine; Catecholamine ID RESPONSE-INHIBITION; STARTLE; PERFORMANCE; DISORDERS; COGNITION; ADOLESCENTS; INVOLVEMENT; DYSFUNCTION; MODULATION; BLOCKADE AB Research documents a reciprocal impact of anxiety on working memory (WM), although its strength and direction depend on factors like task difficulty. A better understanding of these factors may generate insights into cognitive mechanisms of action involved in anxiety, culminating into treatment implications. By blocking the physiological effects of anxiety, propranolol might also block anxiety interference on WM. Conversely, by improving task-directed attention, methylphenidate might reduce anxiety, or, alternatively, by improving cognitive efficiency and free up processing resources to compute anxiety. To investigate the interplay between induced anxiety and WM, we pharmacologically manipulated either anxiety or cognition, using single doses of 40 mg propranolol (PRO), 20 mg methylphenidate (MPH), or placebo (PLA). In this double-blind parallel-group design study, 60 healthy volunteers (20/drug group) performed a verbal WM task under three loads, 1-, 2- and 3-back, and in two conditions, threat of shock and safety. Startle electromyography (EMG) was used to measure anxiety. Findings were twofold: (1) MPH blocked anxiety interference only on the 3-back WM performance, while PRO or PLA had no effects on anxiety-WM interference, and (2) drugs had no effects on anxiety, but, after controlling for baseline anxiety, MPH enhanced anxiety-potentiated startle during the 3-back task. These findings support that MPH-related improvement of cognitive efficiency permits anxiety to be processed and expressed. In conclusion, MPH may be a useful tool to investigate the mechanisms of interaction between anxiety and WM, particularly those under catecholaminergic control. C1 [Ernst, Monique; Lago, Tiffany; Davis, Andrew; Grillon, Christian] NIMH, Neurobiol Fear & Anxiety, 15K North Dr,Bldg 15K,MSC 2670, Bethesda, MD 20892 USA. RP Ernst, M (reprint author), NIMH, Neurobiol Fear & Anxiety, 15K North Dr,Bldg 15K,MSC 2670, Bethesda, MD 20892 USA. EM ernstm@mail.nih.gov FU National Institute of Mental Health [ZIAMH002798] FX The authors report no conflicts of interest. Financial support of this study was provided by the Intramural Research Program of the National Institute of Mental Health, ZIAMH002798. NR 41 TC 0 Z9 0 U1 4 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD OCT PY 2016 VL 233 IS 19-20 BP 3565 EP 3574 DI 10.1007/s00213-016-4390-y PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA DW5GV UT WOS:000383672500007 PM 27492789 ER PT J AU Meier, HCS Haan, MN de Leon, CFM Simanek, AM Dowd, JB Aiello, AE AF Meier, Helen C. S. Haan, Mary N. de Leon, Carlos F. Mendes Simanek, Amanda M. Dowd, Jennifer B. Aiello, Allison E. TI Early life socioeconomic position and immune response to persistent. infections among elderly Latinos SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE Socioeconomic position; Persistent infections; Life course epidemiology; Latino health ID HELICOBACTER-PYLORI INFECTION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; UNITED-STATES; CYTOMEGALOVIRUS-INFECTION; AUTOIMMUNE-DISEASES; TOXOPLASMA-GONDII; ANTIBODY-TITERS; SEROPREVALENCE; CHILDHOOD; US AB Persistent infections, such as cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), Helicobacter pylori (H. pylori), and Toxoplasma gondii (T. gondii), are common in the U.S. but their prevalence varies by socioeconomic status, It is unclear if early or later life socioeconomic position (SEP) is a more salient driver of disparities in immune control of these infections. Using data from the Sacramento Area Latino Study on Aging, we examined whether early or later life SEP was the strongest predictor of immune control later in life by contrasting two life course models, the critical period model and the chain of risk model. Early life SEP was measured as a latent variable, derived from parental education and occupation, and food availability. Indicators for SEP in later life included education level and occupation. Individuals were categorized by immune response to each pathogen (seronegative, low, medium and high) with increasing immune response representing poorer immune control. Cumulative immune response was estimated using a latent profile analysis with higher total immune response representing poorer immune control. Structural equation models were used to examine direct, indirect and total effects of early life SEP on each infection and cumulative immune response, controlling for age and gender. The direct effect of early life SEP on immune response was not statistically significant for the infections or cumulative immune response. Higher early life SEP was associated with lower immune response for T gondii, H. pylori and cumulative immune response through pathways mediated by later life SEP. For CMV, higher early life SEP was both directly associated and partially mediated by later life SEP. No association was found between SEP and HSV-1. Findings from this study support a chain of risk model, whereby early life SEP acts through later life SEP to affect immune response to persistent infections in older age. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Meier, Helen C. S.] Natl Inst Environm Hlth Sci, Epidemiol Branch, 171 TW Alexander Dr,POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. [Haan, Mary N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, 550 15th St, San Francisco, CA 94158 USA. [de Leon, Carlos F. Mendes] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ctr Social Epidemiol & Populat Hlth, 1415 Washington Hts, Ann Arbor, MI 48109 USA. [Simanek, Amanda M.] Univ Wisconsin, Joseph J Zilber Sch Publ Hlth, POB 413, Milwaukee, WI 53201 USA. [Dowd, Jennifer B.] CUNY, Hunter Coll, CUNY Sch Publ Hlth, Dept Epidemiol & Biostat, 2180 Third Ave, New York, NY 10035 USA. [Aiello, Allison E.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, 135 Dauer Dr 2101B McGavran Greenberg Hall, Chapel Hill, NC 27599 USA. RP Aiello, AE (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, 135 Dauer Dr 2101B McGavran Greenberg Hall, Chapel Hill, NC 27599 USA. EM helen.meier@nih.gov; mary.haan@ucsf.edu; cmendes@umich.edu; simaneka@uwm.edu; jdowd@hunter.cuny.edu; aaiello@email.unc.edu OI Meier, Helen/0000-0003-4400-0216; Dowd, Jennifer/0000-0003-2006-5656 FU National Institute on Aging, National Institutes of Health [R01AG012975]; Intramural Research Program of the NIH, National Institute of Environmental Health Sciences; [P60MD002249]; [R01DA022702]; [R01DK087864] FX Funding for the SALSA study was aided by a grant from the National Institute on Aging, National Institutes of Health: R01AG012975. Additional support for this work from grants: P60MD002249, R01DA022702, and R01DK087864. We thank Brisa Sanchez for her statistical consultation and the Stanley Neurovirology Laboratory at Johns Hopkins University, particularly Drs. Robert Yolken and Fuller Torrey, for performing the laboratory assays. This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 62 TC 0 Z9 0 U1 9 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD OCT PY 2016 VL 166 BP 77 EP 85 DI 10.1016/j.socscimed.2016.07.004 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA DY0LL UT WOS:000384788200010 PM 27543684 ER PT J AU Stanko, JP Kissling, GE Chappell, VA Fenton, SE AF Stanko, Jason P. Kissling, Grace E. Chappell, Vesna A. Fenton, Suzanne E. TI Differences in the Rate of in Situ Mammary Gland Development and Other Developmental Endpoints in Three Strains of Female Rat Commonly Used in Mammary Carcinogenesis Studies: Implications for Timing of Carcinogen Exposure SO TOXICOLOGIC PATHOLOGY LA English DT Article DE mammary gland; carcinogenesis; female reproduction; development; epithelium; animal models; rat ID LONG-EVANS RATS; BREAST-CANCER RISK; ESTROGEN-RECEPTOR; ENVIRONMENTAL EXPOSURES; PERFLUOROOCTANOIC ACID; ENDOCRINE DISRUPTORS; PRENATAL EXPOSURE; PFOA EXPOSURE; RODENT MODELS; KNOCKOUT MICE AB The potential of chemicals to alter susceptibility to mammary tumor formation is often assessed using a carcinogen-induced study design in various rat strains. The rate of mammary gland (MG) development must be considered so that the timing of carcinogen administration is impactful. In this study, in situ MG development was assessed in females of the Harlan Sprague-Dawley (Hsd:SD), Charles River Sprague-Dawley (Crl:SD), and Charles River Long-Evans (Crl:LE) rat strains at postnatal days 25, 33, and 45. Development was evaluated by physical assessment of growth parameters, developmental scoring, and quantitative morphometric analysis. Although body weight (BW) was consistently lower and day of vaginal opening (VO) occurred latest in female Hsd:SD rats, they exhibited accelerated pre- and peripubertal MG development compared to other strains. Glands of Crl:SD and Crl:LE rats exhibited significantly more terminal end buds (TEBs) and TEB/mm than Hsd:SD rats around the time of VO. These data suggest a considerable difference in the rate of MG development across commonly used strains, which is independent of BW and timing of VO. In mammary tumor induction studies employing these strains, administration of the carcinogen should be timed appropriately, based on strain, to specifically target the peak of TEB occurrence. C1 [Stanko, Jason P.; Chappell, Vesna A.; Fenton, Suzanne E.] NIEHS, NTPL, DNTP, 111 TW Alexander Dr,MD E1-08, Res Triangle Pk, NC 27709 USA. [Kissling, Grace E.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Fenton, SE (reprint author), NIEHS, NTPL, DNTP, 111 TW Alexander Dr,MD E1-08, Res Triangle Pk, NC 27709 USA. EM fentonse@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999, ZIA ES102785-02] NR 70 TC 0 Z9 0 U1 7 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 EI 1533-1601 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD OCT PY 2016 VL 44 IS 7 BP 1021 EP 1033 DI 10.1177/0192623316655222 PG 13 WC Pathology; Toxicology SC Pathology; Toxicology GA DY1EL UT WOS:000384837600011 PM 27613105 ER PT J AU Filgo, AJ Foley, JF Puvanesarajah, S Borde, AR Midkiff, BR Reed, CE Chappell, VA Alexander, LB Borde, PR Troester, MA Bouknight, SAH Fenton, SE AF Filgo, Adam J. Foley, Julie F. Puvanesarajah, Samantha Borde, Aditi R. Midkiff, Bentley R. Reed, Casey E. Chappell, Vesna A. Alexander, Lydia B. Borde, Pretish R. Troester, Melissa A. Bouknight, Schantel A. Hayes Fenton, Suzanne E. TI Mammary Gland Evaluation in Juvenile Toxicity Studies: Temporal Developmental Patterns in the Male and Female Harlan Sprague-Dawley Rat SO TOXICOLOGIC PATHOLOGY LA English DT Article DE mammary gland; atlas; HSD; rat; developmental exposure; steroid receptor; histology; whole mount ID ENDOCRINE-DISRUPTING CHEMICALS; BREAST DEVELOPMENT; IN-UTERO; GONADOTROPIN-SECRETION; PRENATAL EXPOSURE; ESTROGEN-RECEPTOR; GENE-EXPRESSION; ANIMAL-MODELS; DIFFERENTIATION; MOUSE AB There are currently no reports describing mammary gland development in the Harlan Sprague-Dawley (HSD) rat, the current strain of choice for National Toxicology Program (NTP) testing. Our goals were to empower the NTP, contract labs, and other researchers in understanding and interpreting chemical effects in this rat strain. To delineate similarities/differences between the female and male mammary gland, data were compiled starting on embryonic day 15.5 through postnatal day 70. Mammary gland whole mounts, histology sections, and immunohistochemically stained tissues for estrogen, progesterone, and androgen receptors were evaluated in both sexes; qualitative and quantitative differences are highlighted using a comprehensive visual timeline. Research on endocrine disrupting chemicals in animal models has highlighted chemically induced mammary gland anomalies that may potentially impact human health. In order to investigate these effects within the HSD strain, 2,3,7,8-tetrachlorodibenzo-p-dioxin, diethylstilbestrol, or vehicle control was gavage dosed on gestation day 15 and 18 to demonstrate delayed, accelerated, and control mammary gland growth in offspring, respectively. We provide illustrations of normal and chemically altered mammary gland development in HSD male and female rats to help inform researchers unfamiliar with the tissue and may facilitate enhanced evaluation of both male and female mammary glands in juvenile toxicity studies. C1 [Filgo, Adam J.] Univ N Carolina, Sch Med, Curriculum Toxicol, Chapel Hill, NC USA. [Filgo, Adam J.; Borde, Aditi R.; Reed, Casey E.; Chappell, Vesna A.; Alexander, Lydia B.; Borde, Pretish R.; Fenton, Suzanne E.] NIEHS, NTP Lab, Div NTP, NIH, 111 TW Alexander Dr,Bldg 101,MD E1-08, Res Triangle Pk, NC 27709 USA. [Foley, Julie F.] NIEHS, Cellular & Mol Pathol Branch, Div NTP, NIH, Res Triangle Pk, NC 27709 USA. [Puvanesarajah, Samantha; Troester, Melissa A.] UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. [Midkiff, Bentley R.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA. [Troester, Melissa A.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Bouknight, Schantel A. Hayes] Charles River Labs, Pathol Associates Inc, Durham, NC USA. RP Fenton, SE (reprint author), NIEHS, NTP Lab, Div NTP, NIH, 111 TW Alexander Dr,Bldg 101,MD E1-08, Res Triangle Pk, NC 27709 USA. EM fentonse@niehs.nih.gov FU NIEHS Individual Research Training Award; NIEHS Summer Intern Program FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Adam J. Filgo was funded by a NIEHS Individual Research Training Award. Aditi R. Borde, Lydia B. Alexander, and Pretish R. Borde were funded by the NIEHS Summer Intern Program. NR 73 TC 0 Z9 0 U1 4 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 EI 1533-1601 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD OCT PY 2016 VL 44 IS 7 BP 1034 EP 1058 DI 10.1177/0192623316663864 PG 25 WC Pathology; Toxicology SC Pathology; Toxicology GA DY1EL UT WOS:000384837600012 PM 27613106 ER PT J AU Tucker, DK Foley, JF Hayes-Bouknight, SA Fenton, SE AF Tucker, Deirdre K. Foley, Julie F. Hayes-Bouknight, Schantel A. Fenton, Suzanne E. TI Preparation of High-quality Hematoxylin and Eosin-stained Sections from Rodent Mammary Gland Whole Mounts for Histopathologic Review SO TOXICOLOGIC PATHOLOGY LA English DT Article DE mammary gland; whole mount; contralateral; development; breast; pathology AB Identifying environmental exposures that cause adverse mammary gland outcomes in rodents is a first step in disease prevention in humans and domestic pets. "Whole mounts" are an easy and inexpensive tissue preparation method that can elucidate typical or abnormal mammary gland morphology in rodent studies. Here, we propose procedures to facilitate the use of whole mounts for histological identification of grossly noted tissue alterations. We noted lesions in mammary whole mounts from 14-month-old CD-1 mice that were not found in the contralateral gland hematoxylin and eosin (H&E)-stained section. Whole mounts were removed from the slide and carefully processed to produce high-quality histological sections that mirrored the quality of the original H&E-stained section in order to properly diagnose the unidentified gross abnormalities. Incorporation of this method into testing protocols that focus on human relevant chemical and endocrine disruptors exposure will increase the chances of identifying lesions in the gland and reduce the risk of false negative findings. This method can be especially invaluable when lesions are not always palpable during the course of the study or visible at necropsy, or when a single cross section of the mammary gland is otherwise used for detecting lesions. C1 [Tucker, Deirdre K.] Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC USA. [Tucker, Deirdre K.; Fenton, Suzanne E.] NIEHS, DNTP, NTP Lab, NIH, 111 TW Alexander Dr,MD E1-08, Res Triangle Pk, NC USA. [Foley, Julie F.] NIEHS, DNTP, Cellular & Mol Pathol Branch, NIH, Res Triangle Pk, NC USA. [Hayes-Bouknight, Schantel A.] Charles River Labs Inc, Durham, NC USA. RP Fenton, SE (reprint author), NIEHS, DNTP, NTP Lab, NIH, 111 TW Alexander Dr,MD E1-08, Res Triangle Pk, NC USA. EM fentonse@niehs.nih.gov FU NIEHS Individual Research Training Award FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Deirdre K. Tucker was funded by a NIEHS Individual Research Training Award. NR 10 TC 0 Z9 0 U1 3 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 EI 1533-1601 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD OCT PY 2016 VL 44 IS 7 BP 1059 EP 1064 DI 10.1177/0192623316660769 PG 6 WC Pathology; Toxicology SC Pathology; Toxicology GA DY1EL UT WOS:000384837600013 PM 27474221 ER PT J AU Patial, S Blackshear, PJ AF Patial, Sonika Blackshear, Perry J. TI Tristetraprolin as a Therapeutic Target in Inflammatory Disease SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID ZINC-FINGER DOMAIN; AU-RICH ELEMENT; MESSENGER-RNA; TNF-ALPHA; ANTISENSE OLIGONUCLEOTIDES; PROTEIN TRISTETRAPROLIN; RHEUMATOID-ARTHRITIS; DEFICIENCY SYNDROME; GLOBAL ANALYSIS; MICE AB Members of the tristetraprolin (TTP) family of RNA-binding proteins are found in all major eukaryotic groups. TTP family members, from plants through humans, can bind adenosine-uridine rich elements in target mRNAs with high affinity. In mammalian cells, these proteins then promote deadenylation and decay of target transcripts. Four such proteins are found in mice, of which the best studied is TTP. When the gene encoding TTP is disrupted in mice, the animals develop a severe syndrome of arthritis, autoimmunity, cachexia, dermatitis, and myeloid hyperplasia. Conversely, recent overexpression studies have demonstrated protection against several experimental models of immune inflammatory disease. This endogenous anti-inflammatory protein could serve as the basis for novel approaches to therapy of similar conditions in humans. C1 [Patial, Sonika; Blackshear, Perry J.] NIEHS, Signal Transduct Lab, POB 12233, Res Triangle Pk, NC 27709 USA. [Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. [Patial, Sonika] Louisiana State Univ, Sch Vet Med, LADDL, Baton Rouge, LA 70803 USA. RP Blackshear, PJ (reprint author), NIEHS, Signal Transduct Lab, POB 12233, Res Triangle Pk, NC 27709 USA.; Blackshear, PJ (reprint author), Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.; Blackshear, PJ (reprint author), Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. EM black009@niehs.nih.gov FU Intramural Program of the National Institute of Environmental Health Sciences, National Institutes of Health FX We are grateful to the members of our laboratory for many useful discussions, and to Drs Mike Fessier and Don Cook for helpful comments on the manuscript. This work was supported by the Intramural Program of the National Institute of Environmental Health Sciences, National Institutes of Health. NR 47 TC 1 Z9 1 U1 2 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD OCT PY 2016 VL 37 IS 10 BP 811 EP 821 DI 10.1016/j.tips.2016.07.002 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DY1MA UT WOS:000384857900003 PM 27503556 ER PT J AU Carney, DM Moroney, E Machlin, L Hahn, S Savage, JE Lee, M Towbin, KA Brotman, MA Pine, DS Leibenluft, E Roberson-Nay, R Hettema, JM AF Carney, Dever M. Moroney, Elizabeth Machlin, Laura Hahn, Shannon Savage, Jeanne E. Lee, Minyoung Towbin, Kenneth A. Brotman, Melissa A. Pine, Daniel S. Leibenluft, Ellen Roberson-Nay, Roxann Hettema, John M. TI The Twin Study of Negative Valence Emotional Constructs SO TWIN RESEARCH AND HUMAN GENETICS LA English DT Article DE negative valence; anxiety; internalizing; twin study ID BIPOLAR DISORDER; PANIC DISORDER; BEHAVIORAL-INHIBITION; ANXIETY DISORDERS; NEURAL MECHANISMS; SELF-REPORT; CHILDREN; THREAT; SCALE; FEAR AB The Twin Study of Negative Valence Emotional Constructs is a multi-site study designed to examine the relationship between a broad selection of potential measures designed to assess putative endophenotypes for negative valence systems (NVS) and early symptoms of internalizing disorders (IDs). In this article, we describe the sample characteristics, data collection protocols, and measures used. Pre-adolescent Caucasian twin pairs were recruited through the Mid-Atlantic Twin Registry; data collection began in February of 2013. Enrolled twins completed various dimensional self-report measures along with cognitive, emotional, and psychophysiological tasks designed to assess NVS function. Parents also completed surveys about their twins and themselves. In addition, a subset of the twins also participated in a neuroimaging protocols. Data collection is in the final stages, and preliminary analyses are underway. The findings will potentially expand our understanding of the mechanisms by which genetic and environmental factors contribute to individual differences in NVS phenotypes and provide new insights into underlying risk factors for IDs. C1 [Carney, Dever M.; Hahn, Shannon; Savage, Jeanne E.; Lee, Minyoung; Roberson-Nay, Roxann; Hettema, John M.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. [Carney, Dever M.; Hahn, Shannon; Savage, Jeanne E.; Lee, Minyoung; Roberson-Nay, Roxann; Hettema, John M.] Virginia Commonwealth Univ, Dept Psychiat, POB 980126, Richmond, VA 23298 USA. [Moroney, Elizabeth; Machlin, Laura; Towbin, Kenneth A.; Brotman, Melissa A.; Pine, Daniel S.; Leibenluft, Ellen] NIMH, Emot & Dev Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Hettema, JM (reprint author), Virginia Commonwealth Univ, Dept Psychiat, POB 980126, Richmond, VA 23298 USA. EM john.hettema@vcuhealth.org RI Brotman, Melissa/H-7409-2013 FU National Institutes of Health [R01MH098055, NIMH-IRP-ziamh002781]; Brain and Behavior Research Foundation (BBRF) [21984]; NIH Center for Advancing Translational Research [UL1TR000058] FX This study was supported by the National Institutes of Health (R01MH098055 to JMH and NIMH-IRP-ziamh002781 to DSP) and the Brain and Behavior Research Foundation (BBRF Grant 21984 to JMH). REDCap and the Mid-Atlantic Twin Registry were supported through the NIH Center for Advancing Translational Research Grant Number UL1TR000058. NR 51 TC 1 Z9 1 U1 6 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1832-4274 EI 1839-2628 J9 TWIN RES HUM GENET JI Twin Res. Hum. Genet. PD OCT PY 2016 VL 19 IS 5 BP 456 EP 464 DI 10.1017/thg.2016.59 PG 9 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA DX5NV UT WOS:000384428600007 PM 27457271 ER PT J AU Boccardo, F Valenzano, M Costantini, S Casabona, F Morotti, M Sala, P De Cian, F Molinari, L Spinaci, S Dessalvi, S Campisi, CC Villa, G Campisi, C AF Boccardo, Francesco Valenzano, Mario Costantini, Sergio Casabona, Federico Morotti, Matteo Sala, Paolo De Cian, Franco Molinari, Lidia Spinaci, Stefano Dessalvi, Sara Campisi, Corrado Cesare Villa, Giuseppe Campisi, Corradino TI LYMPHA Technique to Prevent Secondary Lower Limb Lymphedema SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID NODE DISSECTION; VULVAR CANCER; LYMPHATICOVENULAR ANASTOMOSIS; SURGICAL PREVENTION; HEALING APPROACH; LEG LYMPHEDEMA; BREAST-CANCER; RISK-FACTORS; FOLLOW-UP; MICROSURGERY AB Inguinofemoral lymphadenectomy carries a high risk of lower limb lymphedema. This report describes the feasibility of performing multiple lymphatic-venous anastomoses (MLVA) after inguinofemoral lymph node completion (LYMPHA technique) and the possible benefit of LYMPHA for preventing lymphedema. Between February, 2011 and October, 2014, 11 patients with vulvar cancer and 16 patients with melanoma of the trunk requiring inguinofemoral lymphadenectomy underwent lymph node dissection and the LYMPHA technique. Blue dye was injected into the thigh 10 min before surgery. Lymphatics afferent to the blue nodes were used to perform MLVA using a collateral branch of the great saphenous vein. The mean age of patients in the vulvar cancer group was 52 years (range, 48-75 years). The melanoma group comprised seven men and nine women with a mean age of 41 years (range, 37-56 years). Of the 16 patients, 5 with vulvar cancer underwent bilateral inguinofemoral lymphadenectomy, whereas the remaining 6 patients with vulvar cancer and all 16 patients with melanoma of the trunk had unilateral node dissection. All the patients were treated by the LYMPHA technique. No lymphocele or infectious complications occurred. Transient lower-extremity edema occurred for one melanoma patient (6.25 %), which resolved after 2 months, and permanent lower-extremity edema occurred for one patient (9 %) with vulvar cancer. The LYMPHA technique appears to be feasible, safe, and effective for the prevention of lower limb lymphedema, thereby improving the patient's quality of life and decreasing health care costs. C1 [Boccardo, Francesco; Molinari, Lidia; Spinaci, Stefano; Dessalvi, Sara; Campisi, Corrado Cesare; Campisi, Corradino] Univ Genoa, Natl Canc Inst Canc Res, IRCCS S Martino Hosp IST, Unit Lymphat Surg,Dept Surg, Genoa, Italy. [Valenzano, Mario; Costantini, Sergio; Casabona, Federico; Morotti, Matteo; Sala, Paolo] Univ Genoa, Natl Canc Inst, S Martino Hosp, Dept Obstet & Gynecol, Genoa, Italy. [De Cian, Franco] Univ Genoa, Natl Canc Inst, S Martino Hosp, Unit Oncol Surg,Dept Surg, Genoa, Italy. [Villa, Giuseppe] Univ Genoa, Natl Canc Inst, S Martino Hosp, Unit Nucl Med,Dept Surg, Genoa, Italy. RP Boccardo, F (reprint author), Univ Genoa, Natl Canc Inst Canc Res, IRCCS S Martino Hosp IST, Unit Lymphat Surg,Dept Surg, Genoa, Italy. EM francesco.boccardo@unige.it NR 25 TC 0 Z9 0 U1 4 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD OCT PY 2016 VL 23 IS 11 BP 3558 EP 3563 DI 10.1245/s10434-016-5282-4 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA DV4XV UT WOS:000382930000023 PM 27221358 ER PT J AU Verma, SC Miyashiro, T AF Verma, Subhash C. Miyashiro, Tim TI Niche-Specific Impact of a Symbiotic Function on the Persistence of Microbial Symbionts within a Natural Host SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID SQUID EUPRYMNA-SCOLOPES; VIBRIO-FISCHERI; LIGHT ORGAN; HAWAII POPULATIONS; LUX GENES; 2 OAHU; COLONIZATION; GUT; MORPHOGENESIS; ORGANIZATION AB How the function of microbial symbionts is affected by their population/consortium structure within a host remains poorly understood. The symbiosis established between Euprymna scolopes and Vibrio fischeri is a well-characterized host-microbe association in which the function and structure of V. fischeri populations within the host are known: V. fischeri populations produce bioluminescence from distinct crypt spaces within a dedicated host structure called the light organ. Previous studies have revealed that luminescence is required for V. fischeri populations to persist within the light organ and that deletion of the lux gene locus, which is responsible for luminescence in V. fischeri, leads to a persistence defect. In this study, we investigated the impact of bioluminescence on V. fischeri population structure within the light organ. We report that the persistence defect is specific to crypt I, which is the most developmentally mature crypt space within the nascent light organ. This result provides insight into the structure/function relationship that will be useful for future mechanistic studies of squid-Vibrio symbiosis. In addition, our report highlights the potential impact of the host developmental program on the spatiotemporal dynamics of host-microbe interactions. C1 [Verma, Subhash C.; Miyashiro, Tim] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. [Verma, Subhash C.] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. RP Miyashiro, T (reprint author), Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. EM tim14@psu.edu FU HHS \ National Institutes of Health (NIH) [097032] FX This work, including the efforts of Tim Miyashiro, was funded by HHS vertical bar National Institutes of Health (NIH) (097032). NR 40 TC 0 Z9 0 U1 15 U2 15 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 EI 1098-5336 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD OCT PY 2016 VL 82 IS 19 BP 5990 EP 5996 DI 10.1128/AEM.01770-16 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA DX0JX UT WOS:000384048700026 PM 27474717 ER PT J AU Adams, MJ Lefkowitz, EJ King, AMQ Harrach, B Harrison, RL Knowles, NJ Kropinski, AM Krupovic, M Kuhn, JH Mushegian, AR Nibert, M Sabanadzovic, S Sanfacon, H Siddell, SG Simmonds, P Varsani, A Zerbini, FM Gorbalenya, AE Davison, AJ AF Adams, Michael J. Lefkowitz, Elliot J. King, Andrew M. Q. Harrach, Balazs Harrison, Robert L. Knowles, Nick J. Kropinski, Andrew M. Krupovic, Mart Kuhn, Jens H. Mushegian, Arcady R. Nibert, Max Sabanadzovic, Sead Sanfacon, Helene Siddell, Stuart G. Simmonds, Peter Varsani, Arvind Zerbini, Francisco Murilo Gorbalenya, Alexander E. Davison, Andrew J. TI Ratification vote on taxonomic proposals to the International Committee on Taxonomy of Viruses (2016) SO ARCHIVES OF VIROLOGY LA English DT Article AB This article lists the changes to virus taxonomy approved and ratified by the International Committee on Taxonomy of Viruses (ICTV) in April 2016. Changes to virus taxonomy (the Universal Scheme of Virus Classification of the International Committee on Taxonomy of Viruses [ICTV]) now take place annually and are the result of a multi-stage process. In accordance with the ICTV Statutes http://www.ictvonline.org/statutes.asp), proposals submitted to the ICTV Executive Committee (EC) undergo a review process that involves input from the ICTV Study Groups (SGs) and Subcommittees (SCs), other interested virologists, and the EC. After final approval by the EC, proposals are then presented for ratification to the full ICTV membership by publication on an ICTV web site (http://www.ictvonline.org/) followed by an electronic vote. The latest set of proposals approved by the EC was made available on the ICTV website by January 2016 (https://talk.ictvonline.org/files/proposals/). A list of these proposals was then emailed on 28 March 2016 to the 148 members of ICTV, namely the EC Members, Life Members, ICTV Subcommittee Members (including the SG chairs) and ICTV National Representatives. Members were then requested to vote on whether to ratify the taxonomic proposals (voting closed on 29 April 2016). C1 [Adams, Michael J.] 24 Woodland Way, Stevenage SG2 8BT, Herts, England. [Lefkowitz, Elliot J.] UAB, Dept Microbiol, BBRB 276,845 19th ST South, Birmingham, AL 35294 USA. [King, Andrew M. Q.] Sunfield, Dawney Hill, Woking GU24 0JB, Surrey, England. [Harrach, Balazs] Hungarian Acad Sci, Vet Med Res Inst, Hungaria Krt 21, H-1143 Budapest, Hungary. [Harrison, Robert L.] USDA, Invas Insect Biocontrol & Behav Lab, 10300 Baltimore Ave,Bldg 007 Barc West, Beltsville, MD 20705 USA. [Knowles, Nick J.] Pirbright Inst, Ash Rd, Pirbright GU24 0NF, Surrey, England. [Kropinski, Andrew M.] Univ Guelph, Dept Food Sci, Guelph, ON N1G 2W1, Canada. [Kropinski, Andrew M.] Univ Guelph, Dept Mol & Cellular Biol, Guelph, ON N1G 2W1, Canada. [Kropinski, Andrew M.] Univ Guelph, Dept Pathobiol, Guelph, ON N1G 2W1, Canada. [Krupovic, Mart] Inst Pasteur, Dept Microbiol, 25 Rue Dr Roux, F-75015 Paris, France. [Kuhn, Jens H.] NIAID, NIH, DCR Integrated Res Facil, Ft Detrick IRF Frederick, B-8200 Res Plaza, Frederick, MD 21702 USA. [Mushegian, Arcady R.] Natl Sci Fdn, Div Mol & Cellular Biosci, 4201 Wilson Blvd, Arlington, VA 22230 USA. [Nibert, Max] Harvard Med Sch, Dept Microbiol & Immunobiol, 77 Ave Louis Pasteur, Boston, MA 02115 USA. [Sabanadzovic, Sead] Mississippi State Univ, Dept Biochem Mol Biol Entomol & Plant Pathol, 100 Old Hwy 12 Mail Stop 9775, Mississippi State, MS 39762 USA. [Sanfacon, Helene] Agr & Agri Food Canada, Summerland Res & Dev Ctr, 4200 Highway 97, Summerland, BC V0H 1Z0, Canada. [Siddell, Stuart G.] Univ Bristol, Dept Cellular & Mol Med, Fac Biomed Sci, Univ Walk, Bristol BS8 1TD, Avon, England. [Simmonds, Peter] Univ Oxford, Nuffield Dept Expt Med, Peter Medawar Bldg,South Pk Rd, Oxford OX1 3PS, England. [Varsani, Arvind] Univ Canterbury, Sch Biol Sci, Private Bag 4800, Christchurch 8140, New Zealand. [Varsani, Arvind] Univ Canterbury, Biomol Interact Ctr, Private Bag 4800, Christchurch 8140, New Zealand. [Zerbini, Francisco Murilo] Univ Fed Vicosa, Dept Fitopatol, BIOAGRO, BR-36570900 Vicosa, MG, Brazil. [Gorbalenya, Alexander E.] Leiden Univ, Dept Med Microbiol, Med Ctr, POB 9600,E4-P,Rm E4-72, NL-2300 RC Leiden, Netherlands. [Davison, Andrew J.] Univ Glasgow, Ctr Virus Res, MRC, Sir Michael Stoker Bldg,464 Bearsden Rd, Glasgow G61 1QH, Lanark, Scotland. RP Adams, MJ (reprint author), 24 Woodland Way, Stevenage SG2 8BT, Herts, England. EM mike.adams.ictv@gmail.com; elliotl@uab.edu; amqking@gmail.com; harrach@vmri.hu; robert.l.harrison@ars.usda.gov; nick.knowles@pirbright.ac.uk; Phage.Canada@gmail.com; mart.krupovic@pasteur.fr; kuhnjens@mail.nih.gov; mushegian2@gmail.com; mnibert@hms.harvard.edu; ssabanadzovic@entomology.msstate.edu; helene.sanfacon@agr.gc.ca; stuart.siddell@bristol.ac.uk; peter.simmonds@ndm.ox.ac.uk; Arvind.varsani@canterbury.ac.nz; zerbini@ufv.br; a.e.gorbalenya@lumc.nl; andrew.davison@glasgow.ac.uk RI Harrach, Balazs/A-3680-2008; Institute, Pirbright/K-4476-2014; Krupovic, Mart/I-4209-2012; Gorbalenya, Alexander/J-4818-2012; Zerbini, Francisco Murilo/N-7359-2013; OI Harrach, Balazs/0000-0002-1410-6469; Krupovic, Mart/0000-0001-5486-0098; Gorbalenya, Alexander/0000-0002-4967-7341; Zerbini, Francisco Murilo/0000-0001-8617-0200; Siddell, Stuart/0000-0002-8702-7868; Sabanadzovic, Sead/0000-0002-2995-2633 FU Medical Research Council [MC_UU_12014/3] NR 69 TC 9 Z9 9 U1 10 U2 10 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0304-8608 EI 1432-8798 J9 ARCH VIROL JI Arch. Virol. PD OCT PY 2016 VL 161 IS 10 BP 2921 EP 2949 DI 10.1007/s00705-016-2977-6 PG 29 WC Virology SC Virology GA DV1LE UT WOS:000382681800036 PM 27424026 ER PT J AU Aggarwal, M Saxena, R Sinclair, E Fu, Y Jacobs, A Dyba, M Wang, X Cruz, I Berry, D Kallakury, B Mueller, SC Agostino, SD Blandino, G Avantaggiati, ML Chung, FL AF Aggarwal, M. Saxena, R. Sinclair, E. Fu, Y. Jacobs, A. Dyba, M. Wang, X. Cruz, I. Berry, D. Kallakury, B. Mueller, S. C. Agostino, S. D. Blandino, G. Avantaggiati, M. L. Chung, F-L TI Reactivation of mutant p53 by a dietary-related compound phenethyl isothiocyanate inhibits tumor growth SO CELL DEATH AND DIFFERENTIATION LA English DT Article ID HUMAN PROSTATE-CANCER; BETA-PHENYLETHYL ISOTHIOCYANATE; INDUCED APOPTOSIS; IN-VIVO; CELLS; SUPPRESSOR; MUTATIONS; MICE; SULFORAPHANE; DEGRADATION AB Mutations in the p53 tumor-suppressor gene are prevalent in human cancers. The majority of p53 mutations are missense, which can be classified into contact mutations (that directly disrupts the DNA-binding activity of p53) and structural mutations (that disrupts the conformation of p53). Both of the mutations can disable the normal wild-type (WT) p53 activities. Nevertheless, it has been amply documented that small molecules can rescue activity from mutant p53 by restoring WT tumor-suppressive functions. These compounds hold promise for cancer therapy and have now entered clinical trials. In this study, we show that cruciferousvegetable- derived phenethyl isothiocyanate (PEITC) can reactivate p53 mutant under in vitro and in vivo conditions, revealing a new mechanism of action for a dietary-related compound. PEITC exhibits growth-inhibitory activity in cells expressing p53 mutants with preferential activity toward p53(R175), one of the most frequent 'hotspot' mutations within the p53 sequence. Mechanistic studies revealed that PEITC induces apoptosis in a p53(R175) mutant-dependent manner by restoring p53 WT conformation and transactivation functions. Accordingly, in PEITC-treated cells the reactivated p53(R175) mutant induces apoptosis by activating canonical WT p53 targets, inducing a delay in S and G2/M phase, and by phosphorylating ATM/CHK2. Interestingly, the growth-inhibitory effects of PEITC depend on the redox state of the cell. Further, PEITC treatments render the p53(R175) mutant sensitive to degradation by the proteasome and autophagy in a concentration-dependent manner. PEITC-induced reactivation of p53(R175) and its subsequent sensitivity to the degradation pathways likely contribute to its anticancer activities. We further show that dietary supplementation of PEITC is able to reactivate WT activity in vivo as well, inhibiting tumor growth in xenograft mouse model. These findings provide the first example of mutant p53 reactivation by a dietary compound and have important implications for cancer prevention and therapy. C1 [Aggarwal, M.; Sinclair, E.; Fu, Y.; Jacobs, A.; Dyba, M.; Cruz, I.; Berry, D.; Kallakury, B.; Mueller, S. C.; Avantaggiati, M. L.; Chung, F-L] Georgetown Univ, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [Saxena, R.] Georgetown Univ, Dept Biochem & Mol & Cellular Biol, Washington, DC 20007 USA. [Wang, X.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Agostino, S. D.; Blandino, G.] Italian Natl Canc Inst Regina Elena, Translat Oncogen Unit, Rome, Italy. RP Avantaggiati, ML; Chung, FL (reprint author), Georgetown Univ, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. EM ma1274@georgetown.edu; flc6@georgetown.edu OI Di Agostino, Silvia/0000-0003-3730-1125; Dyba, Marcin/0000-0001-6311-6877 FU National Cancer Institute at National Institutes of Health [CA100853]; National Cancer Institute at National Institutes of Health (Lombardi Cancer Center Support Grant) [P30 CA51008] FX We thank Dr. Shivendra V Singh (University of Pittsburgh, Pennsylvania, USA) for the ATG5 siRNA and ATG5 antibody; Dr. Darren R Carpizo (The Cancer Institute of New Jersy, New Brunswick, NJ, USA) for the (10)3 MEF transfectants; Dr. Thomas TY Wang, Dr. Michael Johnson and Dr. Priscilla Furth for comments and discussions; and Angela Bai for the proofreading. We thank Peter Johnson and Karen Creswell for imaging and Flow Cytometry and Supti Sen and Anna Coffey for Histology and Tissue Shared Resources at Georgetown University. This work is supported by the National Cancer Institute at National Institutes of Health (CA100853 and Lombardi Cancer Center Support Grant P30 CA51008). NR 44 TC 3 Z9 3 U1 14 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 EI 1476-5403 J9 CELL DEATH DIFFER JI Cell Death Differ. PD OCT PY 2016 VL 23 IS 10 BP 1615 EP 1627 DI 10.1038/cdd.2016.48 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DX1QO UT WOS:000384142300005 PM 27258787 ER PT J AU Shah, P Kerns, E Nguyen, DT Obach, RS Wang, AQ Zakharov, A McKew, J Simeonov, A Hop, CECA Xu, X AF Shah, Pranav Kerns, Edward Dac-Trung Nguyen Obach, R. Scott Wang, Amy Q. Zakharov, Alexey McKew, John Simeonov, Anton Hop, Cornelis E. C. A. Xu, Xin TI An Automated High-Throughput Metabolic Stability Assay Using an Integrated High-Resolution Accurate Mass Method and Automated Data Analysis Software SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID DRUG-METABOLISM; QUANTITATIVE-ANALYSIS; MICROSOMAL STABILITY; SPECTROMETRY; CANDIDATES; CLEARANCE; OPTIMIZATION; HEPATOCYTES; MODELS; PLASMA AB Advancement of in silico tools would be enabled by the availability of data for metabolic reaction rates and intrinsic clearance (CLint) of a diverse compound structure data set by specific metabolic enzymes. Our goal is to measure CLint for a large set of compounds with each major human cytochrome P450 (P450) isozyme. To achieve our goal, it is of utmost importance to develop an automated, robust, sensitive, high-throughput metabolic stability assay that can efficiently handle a large volume of compound sets. The substrate depletion method [in vitro half-life (t(1/2)) method] was chosen to determine CLint. The assay (384-well format) consisted of three parts: 1) a robotic system for incubation and sample cleanup; 2) two different integrated, ultraperformance liquid chromatography/mass spectrometry (UPLC/MS) platforms to determine the percent remaining of parent compound, and 3) an automated data analysis system. The CYP3A4 assay was evaluated using two long t(1/2) compounds, carbamazepine and antipyrine (t(1/2) > 30 minutes); one moderate t(1/2) compound, ketoconazole (10 < t(1/2) < 30 minutes); and two short t(1/2) compounds, loperamide and buspirone (t(1/2) < 10 minutes). Interday and intraday precision and accuracy of the assay were within acceptable range (similar to 12%) for the linear range observed. Using this assay, CYP3A4 CLint and t(1/2) values for more than 3000 compounds were measured. This high-throughput, automated, and robust assay allows for rapid metabolic stability screening of large compound sets and enables advanced computational modeling for individual human P450 isozymes. C1 [Shah, Pranav; Kerns, Edward; Dac-Trung Nguyen; Wang, Amy Q.; Zakharov, Alexey; McKew, John; Simeonov, Anton; Xu, Xin] Natl Ctr Adv Translat Sci, Div Preclin Innovat, 9800 Med Ctr Dr, Rockville, MD 20850 USA. [Obach, R. Scott] Pfizer, Dept Pharmacokinet Dynam & Metab, Groton, CT USA. [Hop, Cornelis E. C. A.] Genentech Inc, Dept Drug Metab & Pharmacokinet, San Francisco, CA 94080 USA. RP Xu, X (reprint author), Natl Ctr Adv Translat Sci, Div Preclin Innovat, 9800 Med Ctr Dr, Rockville, MD 20850 USA. EM xin.xu3@nih.gov FU Intramural Research Program of the National Center for Advancing Translational Sciences/National Institutes of Health FX This work was supported by the Intramural Research Program of the National Center for Advancing Translational Sciences/National Institutes of Health. NR 22 TC 0 Z9 0 U1 3 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 EI 1521-009X J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD OCT PY 2016 VL 44 IS 10 BP 1653 EP 1661 DI 10.1124/dmd.116.072017 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DX0WY UT WOS:000384088300014 PM 27417180 ER PT J AU Noble, JA Nelson, RG Fufaa, GD Kang, P Shafir, SC Galgiani, JN AF Noble, Jason A. Nelson, Robert G. Fufaa, Gudeta D. Kang, Paul Shafir, Shira Chani Galgiani, John N. TI Effect of Geography on the Analysis of Coccidioidomycosis-Associated Deaths, United states SO EMERGING INFECTIOUS DISEASES LA English DT Article ID PIMA-INDIANS; CALIFORNIA; ARIZONA; IMPACT AB Because coccidioidomycosis death rates vary by region, we reanalyzed coccidioidomycosis-associated mortality in the United States by race/ethnicity, then limited analysis to Arizona and California. Coccidioidomycosis-associated deaths were shown to increase among African-Americans but decrease among Native Americans and Hispanics. Separately, in a Native American cohort, diabetes co-varied with coccidioidomycosis-associated death. C1 [Noble, Jason A.; Kang, Paul] Univ Arizona, Coll Med, Phoenix, AZ USA. [Nelson, Robert G.; Fufaa, Gudeta D.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Shafir, Shira Chani] Univ Calif Los Angeles, Los Angeles, CA USA. [Galgiani, John N.] Univ Arizona, Coll Med, Tucson, AZ USA. RP Galgiani, JN (reprint author), Univ Arizona, Coll Med, Valley Fever Ctr Excellence, 1656 East Mabel St, Tucson, AZ 85712 USA. EM spherule@u.arizona.edu NR 12 TC 1 Z9 1 U1 2 U2 2 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 EI 1080-6059 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD OCT PY 2016 VL 22 IS 10 BP 1821 EP 1823 DI 10.3201/eid2210.160696 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA DX4YQ UT WOS:000384387400021 PM 27649029 ER PT J AU Dennis, KK Auerbach, SS Balshaw, DM Cui, YX Fallin, MD Smith, M Spira, A Sumner, S Miller, GW AF Dennis, Kristine K. Auerbach, Scott S. Balshaw, David M. Cui, Yuxia Fallin, Margaret Daniele Smith, MartynT. Spira, Avrum Sumner, Susan Miller, Gary W. TI The Importance of the Biological Impact of Exposure to the Concept of the Exposome SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID HUMAN METABOLOME DATABASE; TELOMERE LENGTH; ENVIRONMENTAL-HEALTH; GENE-EXPRESSION; LIFE-STYLE; DISEASE; GENOME; CANCER; RISKS; TECHNOLOGIES AB BACKGROUND: The term "exposome" was originally coined in 2005 and defined as the totality of exposures throughout the lifetime. The exposome provides an excellent scientific framework for studying human health and disease. Recently, it has been suggested that how exposures affect our biology and how our bodies respond to such exposures should be part of the exposome. OBJECTIVES: The authors describe the biological impact of the exposome and outline many of the targets and processes that can be assessed as part of a comprehensive analysis of the exposome. DISCUSSION: The processes that occur downstream from the initial interactions with exogenous and endogenous compounds determine the biological impact of exposures. If the effects are not considered in the same context as the exposures, it will be difficult to determine cause and effect. The exposome and biology are interactive-changes in biology due to the environment change one's vulnerability to subsequent exposures. Additionally, highly resilient individuals are able to withstand environmental exposures with minimal effects to their health. We expect that the vast majority of exposures are transient, and chemicals underlying exposures that occurred weeks, months, or years ago are long gone from the body. However, these past chemical exposures often leave molecular fingerprints that may be able to provide information on these past exposures. CONCLUSIONS: Through linking exposures to specific biological responses, exposome research could serve to improve understanding of the mechanistic connections between exposures and health to help mitigate adverse health outcomes across the lifespan. C1 [Dennis, Kristine K.; Miller, Gary W.] Emory Univ, Rollins Sch Publ Hlth, Dept Environm Hlth, 1518 Clifton Rd NE,Mailstop 1518-002-8BB, Atlanta, GA 30322 USA. [Auerbach, Scott S.] NIEHS, Biomol Screening Branch, Div Natl Toxicol Program, NIH,Dept Hlth & Human Resources, POB 12233, Res Triangle Pk, NC 27709 USA. [Balshaw, David M.; Cui, Yuxia] NIEHS, Exposure Response & Technol Branch, Div Extramural Res & Training, NIH,Dept Hlth & Human Resources, POB 12233, Res Triangle Pk, NC 27709 USA. [Fallin, Margaret Daniele] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Smith, MartynT.] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA. [Spira, Avrum] Boston Univ, Sch Med, Div Computat Biomed, Boston, MA 02118 USA. [Sumner, Susan] RTI Int, Discovery Sci, Res Triangle Pk, NC USA. RP Miller, GW (reprint author), Emory Univ, Rollins Sch Publ Hlth, Dept Environm Hlth, 1518 Clifton Rd NE,Mailstop 1518-002-8BB, Atlanta, GA 30322 USA. EM gary.miller@emory.edu FU National Institute of Environmental Health Sciences, National Exposure Assessment Laboratory Network [1U2CES026560, 1U2CES026544] FX G.W.M. receives royalties from his book The Exposome: A Primer. G.W.M. and S.S. received CHEAR (Children's Health Exposure Analysis Resource) awards from the National Institute of Environmental Health Sciences as part of the National Exposure Assessment Laboratory Network to provide targeted and untargeted environmental exposure and biological response analyses in human samples (1U2CES026560 and 1U2CES026544). A.S. is the founder of AllegroDx, Inc., Maynard, MA and a consultant to Veracyte, Inc., South San Francisco, CA. S.S. is employed by Discovery Sciences, RTI International, Research Triangle Park, NC. NR 42 TC 8 Z9 8 U1 8 U2 8 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 OCT PY 2016 VL 124 IS 10 BP 1504 EP 1510 DI 10.1289/EHP140 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA DX4EQ UT WOS:000384334400012 PM 27258438 ER PT J AU Le, NT Michels, FAS Song, MY Zhang, XH Bernstein, AM Giovannucci, EL Fuchs, CS Ogino, S Chan, AT Sinha, R Willett, WC Wu, KN AF Ngoan Tran Le Michels, Fernanda Alessandra Silva Song, Mingyang Zhang, Xuehong Bernstein, Adam M. Giovannucci, Edward L. Fuchs, Charles S. Ogino, Shuji Chan, Andrew T. Sinha, Rashmi Willett, Walter C. Wu, Kana TI A Prospective Analysis of Meat Mutagens and Colorectal Cancer in the Nurses' Health Study and Health Professionals Follow-up Study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; DIETARY HETEROCYCLIC AMINES; NATIONAL DEATH INDEX; COLON-CANCER; MULTIETHNIC COHORT; RED MEAT; COOKING METHODS; RISK FINDINGS; HEME IRON; CONSUMPTION AB BACKGROUND: Heterocyclic amines (HCAs) in cooked meats may play a role in colorectal cancer (CRC) development. OBJECTIVES: We aimed to prospectively examine the association between estimated intakes of HCAs and meat-derived mutagenicity (MDM) in two cohorts of health professionals, the Health Professionals Follow-up Study (HPFS) and the Nurses' Health Study (NHS). METHODS: In 29,615 men and 65,875 women, intake of the HCAs 2-amino-3,8-dimethylimidazo(4,5-j) quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo(4,5-b) pyridine (PhIP), 2-amino-3,4,8-trimethylimidazo(4,5-f) quinoxaline (DiMeIQx), and MDM was estimated using a 1996 cooking questionnaire, the 1994 food frequency questionnaire, and an online database. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) and to adjust for potential confounders. Estimates for both cohorts were pooled using random-effects meta-analysis. RESULTS: Between 1996 and 2010, 418 male and 790 female CRC cases were identified. Meat mutagen intake was not statistically significantly associated with risk of CRC [highest vs. lowest quintile, pooled HR (95% CI) for MeIQx: 1.12 (0.93, 1.34), p for trend 0.23; PhIP: 1.10 (0.90, 1.33), p for trend 0.35; MDM: 1.03 (0.86, 1.24), p for trend 0.75] or subtypes of CRC defined by tumor location (proximal or distal colon, or rectum). When analyzed by source of meat, PhIP from red but not from white meat was nonsignificantly positively associated with CRC and significantly positively associated with proximal cancers [HR (95% CI) per standard deviation increase of log-transformed intake: PhIP red meat: CRC: 1.06 (0.99, 1.12), proximal: 1.11 (1.02, 1.21); PhIP white meat: CRC: 0.99 (0.94, 1.04), proximal: 1.00 (0.93, 1.09)]. CONCLUSIONS: Estimated intakes of meat mutagens were not significantly associated with CRC risk over 14 years of follow-up in the NHS and HPFS cohorts. Results for PhIP from red but not from white meat warrant further investigation. C1 [Ngoan Tran Le] Hanoi Med Univ, Dept Occupat Hlth, Hanoi, Vietnam. [Ngoan Tran Le; Michels, Fernanda Alessandra Silva; Song, Mingyang; Giovannucci, Edward L.; Willett, Walter C.; Wu, Kana] Harvard TH Chan Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. [Song, Mingyang; Chan, Andrew T.] Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA. [Song, Mingyang; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Song, Mingyang; Zhang, Xuehong; Giovannucci, Edward L.; Fuchs, Charles S.; Ogino, Shuji; Chan, Andrew T.; Willett, Walter C.] Harvard Med Sch, Boston, MA USA. [Song, Mingyang; Giovannucci, Edward L.; Ogino, Shuji; Willett, Walter C.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Zhang, Xuehong; Giovannucci, Edward L.; Ogino, Shuji; Chan, Andrew T.; Willett, Walter C.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Bernstein, Adam M.] Rally Hlth, San Francisco, CA USA. [Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Div Mol Pathol Epidemiol, 75 Francis St, Boston, MA 02115 USA. [Sinha, Rashmi] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Le, NT (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM letngoan@hmu.edu.vn FU National Institutes of Health [UM1 CA167552, UM1 CA186107, P50 CA127003, R35 CA197735, P01 CA87969, P01 CA 55075]; Union for International Cancer Control (UICC) American Cancer Society Beginning Investigators Fellowship - American Cancer Society; UICC Yamagiwa-Yoshida Memorial International Cancer Study Grant FX This work was supported by federal grants (National Institutes of Health): UM1 CA167552, UM1 CA186107, P50 CA127003, R35 CA197735, P01 CA87969, and P01 CA 55075. This work has also been supported by a Union for International Cancer Control (UICC) American Cancer Society Beginning Investigators Fellowship funded by the American Cancer Society and by a UICC Yamagiwa-Yoshida Memorial International Cancer Study Grant to N.T.L. NR 64 TC 2 Z9 2 U1 9 U2 9 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 OCT PY 2016 VL 124 IS 10 BP 1529 EP 1536 DI 10.1289/EHP238 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA DX4EQ UT WOS:000384334400015 PM 27105317 ER PT J AU Nagrani, R Mhatre, S Rajaraman, P Soerjomataram, I Boffetta, P Gupta, S Parmar, V Badwe, R Dikshit, R AF Nagrani, R. Mhatre, S. Rajaraman, P. Soerjomataram, I. Boffetta, P. Gupta, S. Parmar, V. Badwe, R. Dikshit, R. TI Central obesity increases risk of breast cancer irrespective of menopausal and hormonal receptor status in women of South Asian Ethnicity SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Breast cancer; Central obesity; Menopausal status; Hormone receptor status; South Asian ID BODY-MASS INDEX; ABDOMINAL ADIPOSITY; INSULIN-RESISTANCE; FAT DISTRIBUTION; SIZE; PROFILE; ANTHROPOMETRY; METAANALYSIS; ASSOCIATION; CAUCASIANS AB Background: Current evidence suggests that the relationship between obesity and breast cancer (BC) risk may vary between ethnic groups. Methods: A total of 1633 BC cases and 1504 controls were enrolled in hospital-based case econtrol study in Mumbai, India, from 2009 to 2013. Along with detailed questionnaire, we collected anthropometric measurements on all participants. We used unconditional logistic regression models to estimate odds ratios (ORs) and 95% confidence interval (CI) for BC risk associated with anthropometry measurements, stratified on tumour subtype and menopausal status. Results: Waist-to-hip ratio (WHR) of >= 0.95 was strongly associated with risk of BC compared to WHR <= 0.84 in both premenopausal (OR = 4.3; 95% CI: 2.9-6.3) and postmenopausal women (OR = 3.4; 95% CI: 2.4-4.8) after adjustment for body mass index (BMI). Premenopausal women with a BMI >= 30 were at lower risk compared to women with normal BMI (OR = 0.5; 95% CI: 0.4-0.8). A similar protective effect was observed in women who were postmenopausal for <10 years (OR = 0.6; 95% CI: 0.4-0.9) but not in women who were postmenopausal for >= 10 years (OR = 1.8; 95% CI: 1.1-3.3). Overweight and obese women (BMI: 25-29.9 and >= 30 kg/m(2), respectively) were at increased BC risk irrespective of menopausal status if their WHR >= 0.95. Central obesity (measured in terms of WC and WHR) increased the risk of both premenopausal and postmenopausal BCs irrespective of hormone receptor (HR) status. Conclusions: Central obesity appears to be a key risk factor for BC irrespective of menopausal or HR status in Indian women with no history of hormone replacement therapy. (C) 2016 The Authors. Published by Elsevier Ltd. C1 [Nagrani, R.; Mhatre, S.; Dikshit, R.] Tata Mem Hosp, Ctr Canc Epidemiol, E Borges Rd, Bombay 400012, Maharashtra, India. [Rajaraman, P.] US Natl Canc Inst, Ctr Global Hlth, 9609 Med Ctr Dr, Rockville, MD 20892 USA. [Soerjomataram, I.] Int Agcy Res Canc, Sect Canc Surveillance, 150 Cours Albert Thomas, F-69372 Lyon, France. [Boffetta, P.] Mt Sinai Hosp, Inst Translat Epidemiol, 1 Gustave L Levy Pl, New York, NY 10029 USA. [Gupta, S.] Adv Ctr Treatment Res & Educ Canc, Navi Mumbai 400012, Maharashtra, India. [Parmar, V.; Badwe, R.] Tata Mem Hosp, Dept Surg Oncol, Bombay 400012, Maharashtra, India. RP Dikshit, R (reprint author), Tata Mem Hosp, Ctr Canc Epidemiol, E Borges Rd, Bombay 400012, Maharashtra, India. EM dixr24@hotmail.com OI nagrani, rajini/0000-0002-1708-2319 FU Department of Biotechnology, India [102/IFD/SAN/2935/2012-2013]; International Agency for research on Cancer, France [GEE/08/02-Extension 1] FX The authors would like to thank the funding agencies viz. Department of Biotechnology, India (102/IFD/SAN/2935/2012-2013); International Agency for research on Cancer, France (GEE/08/02-Extension 1). NR 35 TC 0 Z9 0 U1 9 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD OCT PY 2016 VL 66 BP 153 EP 161 DI 10.1016/j.ejca.2016.07.022 PG 9 WC Oncology SC Oncology GA DX0YB UT WOS:000384091400019 PM 27573429 ER PT J AU Maddipati, KR Romero, R Chaiworapongsa, T Chaemsaithong, P Zhou, SL Xu, ZH Tarca, AL Kusanovic, JP Gomez, R Chaiyasit, N Honn, KV AF Maddipati, Krishna Rao Romero, Roberto Chaiworapongsa, Tinnakorn Chaemsaithong, Piya Zhou, Sen-Lin Xu, Zhonghui Tarca, Adi L. Kusanovic, Juan Pedro Gomez, Ricardo Chaiyasit, Noppadol Honn, Kenneth V. TI Lipidomic analysis of patients with microbial invasion of the amniotic cavity reveals up-regulation of leukotriene B-4 SO FASEB JOURNAL LA English DT Article DE infection; inflammation; clinical chorioamnionitis; amniotic fluid; 5-lipoxygenase ID PRETERM PREMATURE RUPTURE; PRO-RESOLVING MEDIATORS; TUMOR-NECROSIS-FACTOR; INTRAAMNIOTIC INFECTION; SPONTANEOUS LABOR; CLINICAL CHORIOAMNIONITIS; HUMAN PARTURITION; FLUID INTERLEUKIN-6; INTACT MEMBRANES; CONCENTRATIONS INCREASE AB Bioactive lipids derived from the metabolism of polyunsaturated fatty acids are important mediators of the inflammatory response. Labor per se is considered a sterile inflammatory process. Intra-amniotic inflammation (IAI) due to microorganisms (i.e., intra-amniotic infection) or danger signals (i.e., sterile IAI) has been implicated in the pathogenesis of preterm labor and clinical chorioamnionitis at term. Early and accurate diagnosis of microbial invasion of the amniotic cavity (MIAC) requires analysis of amniotic fluid (AF). It is possible that IAI caused by microorganisms is associated with a stereotypic lipidomic profile, and that analysis of AF may help in the identification of patients with this condition. To test this hypothesis, we analyzed the fatty acyl lipidome of AF by liquid chromatography-mass spectrometry from patients in spontaneous labor at term and preterm gestations. We report that the AF concentrations of proinflammatory lipid mediators of the 5-lipoxygenase pathway are significantly higher in MIAC than in cases of sterile IAI. These results suggest that the concentrations of 5-lipoxygenase metabolites of arachidonic acid, 5-hydroxyeicosatetraenoic acid, and leukotriene B-4 in particular could serve as potential biomarkers of MIAC. This finding could have important implications for the rapid identification of patients who may benefit from anti-microbial treatment.-Maddipati, K. R., Romero, R., Chaiworapongsa ,T., Chaemsaithong, P., Zhou, S.-L., Xu, Z., Tarca, A. L., Kusanovic, J. P., Gomez, R., Chaiyasit, N., Honn, K. V. Lipidomic analysis of patients with microbial invasion of the amniotic cavity reveals up-regulation of leukotriene B-4. C1 [Maddipati, Krishna Rao; Zhou, Sen-Lin; Honn, Kenneth V.] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. [Maddipati, Krishna Rao; Zhou, Sen-Lin] Wayne State Univ, Sch Med, Lipid Core Facil, Detroit, MI USA. [Chaiworapongsa, Tinnakorn; Chaemsaithong, Piya; Tarca, Adi L.; Chaiyasit, Noppadol] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto; Chaiworapongsa, Tinnakorn; Chaemsaithong, Piya; Xu, Zhonghui; Tarca, Adi L.; Kusanovic, Juan Pedro; Chaiyasit, Noppadol] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Div Intramural Res, Natl Inst Hlth,Dept Hlth & Human Serv, Bethesda, MD USA. [Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Tarca, Adi L.] Wayne State Univ, Dept Comp Sci, Detroit, MI 48202 USA. [Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA. [Kusanovic, Juan Pedro] Hosp Dr Sotero del Rio, Dept Obstet & Gynecol, Ctr Res & Innovat Maternal Fetal Med CIMAF, Santiago, Chile. [Kusanovic, Juan Pedro; Gomez, Ricardo] Pontificia Univ Catolica Chile, Div Obstet & Gynecol, Santiago, Chile. [Gomez, Ricardo] Hosp Clin La Florida, Res & Acad Innovat, Ctr Perinatal Diag CEDIP, Santiago, Chile. RP Maddipati, KR (reprint author), Wayne State Univ, Dept Pathol, 435 Chem Bldg,410 W Warren Ave, Detroit, MI 48202 USA. EM maddipati@wayne.edu FU Perinatology Research Branch, Division of Intramural Research Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, U.S. National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS); NICHD/NIH/DHHS [HHSN275201300006C]; National Center for Research Resources [S10RR027926]; Wayne State University FX This research was supported, in part, by the Perinatology Research Branch, Division of Intramural Research Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, U.S. National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS); and, in part, with Federal funds from NICHD/NIH/DHHS Contract No. HHSN275201300006C; and, in part, by the National Center for Research Resources Grant S10RR027926 and the Perinatal Virtual Discovery Grant from Wayne State University (to K.R.M.). The authors declare no conflicts of interest. NR 91 TC 0 Z9 0 U1 3 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD OCT PY 2016 VL 30 IS 10 BP 3296 EP 3307 DI 10.1096/fj.201600583R PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA DX4DD UT WOS:000384329800004 PM 27312808 ER PT J AU Hu, N Wang, ZM Song, X Wei, LX Kim, BS Freedman, ND Baek, J Burdette, L Chang, J Chung, C Dawsey, SM Ding, T Gao, YT Giffen, C Han, YL Hong, M Huang, J Kim, HS Koh, WP Liao, LDM Mao, YM Qiao, YL Shu, XO Tan, W Wang, CY Wu, C Wu, MJ Xiang, YB Yeager, M Yook, JH Yuan, JM Zhang, P Zhao, XK Zheng, W Song, K Wang, LD Lin, DX Chanock, SJ Goldstein, AM Taylor, PR Abnet, CC AF Hu, Nan Wang, Zhaoming Song, Xin Wei, Lixuan Kim, Byung Sik Freedman, Neal D. Baek, Jiwon Burdette, Laurie Chang, Jiang Chung, Charles Dawsey, Sanford M. Ding, Ti Gao, Yu-Tang Giffen, Carol Han, Yaling Hong, Myunghee Huang, Jia Kim, Hee Sung Koh, Woon-Puay Liao, Linda M. Mao, Yi Min Qiao, You-Lin Shu, Xiao-Ou Tan, Wen Wang, Chaoyu Wu, Chen Wu, Min-Jie Xiang, Yong-Bing Yeager, Meredith Yook, Jeong Hwan Yuan, Jian-Min Zhang, Peng Zhao, Xue-Ke Zheng, Wei Song, Kyuyoung Wang, Li-Dong Lin, Dongxin Chanock, Stephen J. Goldstein, Alisa M. Taylor, Philip R. Abnet, Christian C. TI Genome-wide association study of gastric adenocarcinoma in Asia: a comparison of associations between cardia and non-cardia tumours SO GUT LA English DT Article ID SQUAMOUS-CELL CARCINOMA; HELICOBACTER-PYLORI; SUSCEPTIBILITY LOCI; KOREAN POPULATION; CANCER; ESOPHAGEAL; CHINESE; DIFFUSE; RISK AB Objective Genome-wide association studies (GWAS) of gastric cancer have reported differences in single-nucleotide polymorphism (SNP) associations for tumour subtypes, particularly when divided by location into the gastric cardia versus the non-cardia. Design Here we present results for a GWAS using 2350 East Asian gastric cancer cases divided as 1189 gastric cardia and 1027 gastric non-cardia cases and 2708 controls. We also included up to 3042 cardia cases, 4359 non-cardia cases and 7548 controls for replication from two Chinese studies and one Korean study. From the GWAS, we selected 12 top SNPs for each gastric cancer subtype, 4 top SNPs for total gastric cancer and 1 SNP in MUC1 for replication testing. Results We observed genome-wide significant associations for rs10074991 in PRKAA1 at 5p13.1 for cardia (p=7.36x10(-12)) and non-cardia cancers (p=2.42x10(-23)) with per allele OR (95% CI) for the combined endpoint of 0.80 (0.77 to 0.83). At 6p21.1, rs2294693 near UNC5CL was significantly associated with gastric non-cardia cancer risk (p=2.50x10(-8)), with OR (95% CI) of 1.18 (1.12 to 1.26), but there was only a nominal association for cardia cancer (p=1.47x10(-2)). We also confirmed a previously reported association for rs4072037 in MUC1 with p=6.59x10(-8) for total gastric cancer and similar estimates for cardia and non-cardia cancers. Three SNPs in PSCA previously reported to be associated with gastric non-cardia cancer showed no apparent association for cardia cancer. Conclusions Our results suggest that associations for SNPs with gastric cancer show some different results by tumour location in the stomach. C1 [Hu, Nan; Wang, Zhaoming; Freedman, Neal D.; Burdette, Laurie; Chung, Charles; Dawsey, Sanford M.; Liao, Linda M.; Wang, Chaoyu; Yeager, Meredith; Chanock, Stephen J.; Goldstein, Alisa M.; Taylor, Philip R.; Abnet, Christian C.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Song, Xin; Huang, Jia; Mao, Yi Min; Zhang, Peng; Zhao, Xue-Ke; Wang, Li-Dong] Zhengzhou Univ, Affiliated Hosp 1, Henan Key Lab Esophageal Canc Res, Zhengzhou, Henan, Peoples R China. [Wei, Lixuan; Chang, Jiang; Han, Yaling; Tan, Wen; Wu, Chen; Lin, Dongxin] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Etiol & Carcinogenesis, Beijing, Peoples R China. [Wei, Lixuan; Chang, Jiang; Han, Yaling; Tan, Wen; Wu, Chen; Lin, Dongxin] Peking Union Med Coll, Beijing, Peoples R China. [Kim, Byung Sik; Kim, Hee Sung; Yook, Jeong Hwan] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Surg, Seoul, South Korea. [Baek, Jiwon; Hong, Myunghee; Song, Kyuyoung] Univ Ulsan, Coll Med, Dept Biochem & Mol Biol, Seoul, South Korea. [Burdette, Laurie; Chung, Charles; Yeager, Meredith] NCI, Canc Genome Res Lab, Div Canc Epidemiol & Genet, Adv Technol Program,SAIC Frederick Inc, Frederick, MD 21701 USA. [Ding, Ti] Shanxi Canc Hosp, Taiyuan, Shanxi, Peoples R China. [Gao, Yu-Tang; Xiang, Yong-Bing] Shanghai Canc Inst, Shanghai, Peoples R China. [Giffen, Carol] Informat Management Serv Inc, Silver Spring, MD USA. [Koh, Woon-Puay] Duke NUS Grad Med Sch Singapore, Singapore, Singapore. [Qiao, You-Lin] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Epidemiol, Beijing, Peoples R China. [Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Dept Med, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Wu, Min-Jie] Xinxiang Med Univ, Canc Res Ctr, Xinxiang, Henan, Peoples R China. [Yuan, Jian-Min] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. RP Abnet, CC (reprint author), NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, 9609 Med Ctr Dr,Rm 6e430,MSC 9768, Bethesda, MD 20892 USA. EM abnet@nih.gov RI Zheng, Wei/O-3351-2013; Abnet, Christian/C-4111-2015 OI Zheng, Wei/0000-0003-1226-070X; Abnet, Christian/0000-0002-3008-7843 FU National Cancer Institute [R01CA80205, R01CA144034, R37: CA070867, R01: CA082729, UM: CA173640]; National Natural Science Foundation of China [81472323]; Top Talent Support Project of Zhengzhou University [ZDGD13001]; Innovation Scientists and Technicians Troop Construction Projects of Henan Province [3047]; Mid-career Researcher Program grant through National Research Foundation from the Ministry of Science, Information and Communication Technology (ICT) and Future Planning, Republic of Korea [2014R1A2A1A09005824] FX This work was supported by the intramural research programme of the National Institutes of Health, National Cancer Institute. The Singapore Chinese Health Study was supported by National Cancer Institute grants R01CA80205 and R01CA144034. The Shanghai Women's Health Study was supported by National Cancer Institute grants R37: CA070867 and the Shanghai Men's Health Study was supported by National Cancer Institute grants R01: CA082729 and UM: CA173640. The Henan province study was supported by the National Natural Science Foundation of China, grant number 81472323; the Top Talent Support Project of Zhengzhou University, grant number ZDGD13001; and the Innovation Scientists and Technicians Troop Construction Projects of Henan Province, grant number 3047 to LDW. KS was supported by a Mid-career Researcher Program grant (2014R1A2A1A09005824) through National Research Foundation from the Ministry of Science, Information and Communication Technology (ICT) and Future Planning, Republic of Korea. NR 16 TC 4 Z9 4 U1 5 U2 5 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD OCT PY 2016 VL 65 IS 10 BP 1611 EP 1618 DI 10.1136/gutjnl-2015-309340 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DX5XR UT WOS:000384456500008 PM 26129866 ER PT J AU Scarzello, AJ Jiang, Q Back, T Dang, H Hodge, D Hanson, C Subleski, J Weiss, JM Stauffer, JK Chaisaingmongkol, J Rabibhadana, S Ruchirawat, M Ortaldo, J Wang, XW Norris, PS Ware, CF Wiltrout, RH AF Scarzello, Anthony J. Jiang, Qun Back, Timothy Dang, Hien Hodge, Deborah Hanson, Charlotte Subleski, Jeffrey Weiss, Jonathan M. Stauffer, Jimmy K. Chaisaingmongkol, Jitti Rabibhadana, Siritida Ruchirawat, Mathuros Ortaldo, John Wang, Xin Wei Norris, Paula S. Ware, Carl F. Wiltrout, Robert H. TI LT beta R signalling preferentially accelerates oncogenic AKT-initiated liver tumours SO GUT LA English DT Article ID NF-KAPPA-B; INTRAHEPATIC CHOLANGIOCARCINOMA; HEPATOCELLULAR-CARCINOMA; LYMPHOTOXIN-BETA; HYDRODYNAMIC INJECTION; NEXT-GENERATION; CYCLIN D1; T-CELLS; CANCER; ACTIVATION AB Objectives The relative contributions of inflammatory signalling and sequential oncogenic dysregulation driving liver cancer pathogenesis remain incompletely understood. Lymphotoxin-beta receptor (LT beta R) signalling is critically involved in hepatitis and liver tumorigenesis. Therefore, we explored the interdependence of inflammatory lymphotoxin signalling and specific oncogenic pathways in the progression of hepatic cancer. Design Pathologically distinct liver tumours were initiated by hydrodynamic transfection of oncogenic V-Akt Murine Thymoma Viral Oncogene Homolog 1 (AKT)/beta-catenin or AKT/Notch expressing plasmids. To investigate the relationship of LT beta R signalling and specific oncogenic pathways, LT beta R antagonist (LT beta R-Fc) or agonist (anti-LT beta R) were administered post oncogene transfection. Initiated livers/tumours were investigated for changes in oncogene expression, tumour proliferation, progression, latency and pathology. Moreover, specific LT beta R-mediated molecular events were investigated in human liver cancer cell lines and through transcriptional analyses of samples from patients with intrahepatic cholangiocarcinoma (ICC). Results AKT/beta-catenin-transfected livers displayed increased expression of LT beta and LT beta R, with antagonism of LT beta R signalling reducing tumour progression and enhancing survival. Conversely, enforced LT beta R-activation of AKT/beta-catenin-initiated tumours induced robust increases in proliferation and progression of hepatic tumour phenotypes in an AKT-dependent manner. LT beta R-activation also rapidly accelerated ICC progression initiated by AKT/Notch, but not Notch alone. Moreover, LT beta R-accelerated development coincides with increases of Notch, Hes1, c-MYC, pAKT and beta-catenin. We further demonstrate LT beta R signalling in human liver cancer cell lines to be a regulator of Notch, pAKTser473 and beta-catenin. Transcriptome analysis of samples from patients with ICC links increased LT beta R network expression with poor patient survival, increased Notch1 expression and Notch and AKT/PI3K signalling. Conclusions Our findings link LT beta R and oncogenic AKT signalling in the development of ICC. C1 [Scarzello, Anthony J.; Jiang, Qun; Back, Timothy; Hodge, Deborah; Hanson, Charlotte; Subleski, Jeffrey; Weiss, Jonathan M.; Stauffer, Jimmy K.; Ortaldo, John; Wiltrout, Robert H.] NCI, Canc & Inflamat Program, Ctr Canc Res, Frederick, MD 21701 USA. [Dang, Hien; Wang, Xin Wei] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bldg 37, Bethesda, MD 20892 USA. [Norris, Paula S.; Ware, Carl F.] Sanford Burnham Med Res Inst, Infect & Inflammatory Dis Res Ctr, La Jolla, CA USA. [Chaisaingmongkol, Jitti; Rabibhadana, Siritida; Ruchirawat, Mathuros] Chulabhorn Res Inst, Bangkok, Thailand. RP Wiltrout, RH (reprint author), NCI, Expt Therapeut Sect, Canc & Inflammat Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA. EM wiltrour@mail.nih.gov RI Wang, Xin/B-6162-2009 FU Intramural Research Program of the National Cancer Institute, National Institutes of Health (NCI/NIH); NIH [R01CA164679, P01CA177322, R37AI33068] FX This research was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health (NCI/NIH) and NIH grants R01CA164679, P01CA177322 and R37AI33068 (CFW). NR 50 TC 2 Z9 2 U1 4 U2 4 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD OCT PY 2016 VL 65 IS 10 BP 1765 EP U203 DI 10.1136/gutjnl-2014-308810 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DX5XR UT WOS:000384456500022 PM 26206664 ER PT J AU Yu, KR Natanson, H Dunbar, CE AF Yu, Kyung-Rok Natanson, Hannah Dunbar, Cynthia E. TI Gene Editing of Human Hematopoietic Stem and Progenitor Cells: Promise and Potential Hurdles SO HUMAN GENE THERAPY LA English DT Review ID ZINC-FINGER NUCLEASES; RNA-GUIDED ENDONUCLEASE; SEVERE COMBINED IMMUNODEFICIENCY; GENOME-WIDE ANALYSIS; CRISPR-CAS SYSTEM; STEM/PROGENITOR CELLS; IN-VIVO; TRANSCRIPTION FACTOR; LENTIVIRAL VECTORS; THERAPY AB Hematopoietic stem and progenitor cells (HSPCs) have great therapeutic potential because of their ability to both self-renew and differentiate. It has been proposed that, given their unique properties, a small number of genetically modified HSPCs could accomplish lifelong, corrective reconstitution of the entire hematopoietic system in patients with various hematologic disorders. Scientists have demonstrated that gene addition therapies-targeted to HSPCs and using integrating retroviral vectors-possess clear clinical benefits in multiple diseases, among them immunodeficiencies, storage disorders, and hemoglobinopathies. Scientists attempting to develop clinically relevant gene therapy protocols have, however, encountered a number of unexpected hurdles because of their incomplete knowledge of target cells, genomic control, and gene transfer technologies. Targeted gene-editing technologies using engineered nucleases such as ZFN, TALEN, and/or CRISPR/Cas9 RGEN show great clinical promise, allowing for the site-specific correction of disease-causing mutations-a process with important applications in autosomal dominant or dominant-negative genetic disorders. The relative simplicity of the CRISPR/Cas9 system, in particular, has sparked an exponential increase in the scientific community's interest in and use of these gene-editing technologies. In this minireview, we discuss the specific applications of gene-editing technologies in human HSPCs, as informed by prior experience with gene addition strategies. HSPCs are desirable but challenging targets; the specific mechanisms these cells evolved to protect themselves from DNA damage render them potentially more susceptible to oncogenesis, especially given their ability to self-renew and their long-term proliferative potential. We further review scientists' experience with gene-editing technologies to date, focusing on strategies to move these techniques toward implementation in safe and effective clinical trials. C1 [Yu, Kyung-Rok; Natanson, Hannah; Dunbar, Cynthia E.] NHLBI, Hematol Branch, NIH, Room 4E-5132,CRC Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. RP Dunbar, CE (reprint author), NHLBI, Hematol Branch, NIH, Room 4E-5132,CRC Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. EM dunbarc@nhlbi.nih.gov FU National Heart, Lung, and Blood Institute FX The authors are supported by funding through the intramural research program of the National Heart, Lung, and Blood Institute. NR 72 TC 0 Z9 0 U1 29 U2 29 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT PY 2016 VL 27 IS 10 BP 729 EP 740 DI 10.1089/hum.2016.107 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA DX5ZY UT WOS:000384462600002 ER PT J AU Li, YC Fariss, RN Qian, JW Cohen, ED Qian, HH AF Li, Yichao Fariss, Robert N. Qian, Jennifer W. Cohen, Ethan D. Qian, Haohua TI Light-Induced Thickening of Photoreceptor Outer Segment Layer Detected by Ultra-High Resolution OCT Imaging SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE optical coherence tomography; subretinal space; light/dark adaptation; outer segments; retinal pigment epithelium ID OPTICAL COHERENCE TOMOGRAPHY; SPACE SURROUNDING PHOTORECEPTORS; RAT RETINA; IN-VIVO; INTERPHOTORECEPTOR MATRIX; DEPENDENT HYDRATION; POSTERIOR SEGMENT; PHAGOCYTOSIS; PHOTOSTASIS; BANDS AB PURPOSE. We examined if light induces changes in the retinal structure that can be observed using optical coherence tomography (OCT). METHODS. Normal C57BL/6J mice ( age 3-6 months) adapted to either room light (15 minutes to similar to 5 hours, 50-500 lux) or darkness (overnight) were imaged using a Bioptigen UHR-OCT system. Confocal histologic images were obtained from mice killed under light- or dark-adapted conditions. RESULTS. The OCT image of eyes adapted to room light exhibited significant increases (6.1 +/- 0.8 mu m, n = 13) in total retina thickness compared to the same eyes after overnight dark adaptation. These light- adapted retinal thickness changes occurred mainly in the outer retina, with the development of a hyporeflective band between the RPE and photoreceptor-tip layers. Histologic analysis revealed a light- evoked elongation between the outer limiting membrane and Bruch's membrane from 45.8 +/- 1.7 mu m in the dark (n = 5) to 52.1 +/- 3.7 mu m (n = 5) in the light. Light-adapted retinas showed an increase of actin staining in RPE apical microvilli at the same location as the hyporeflective band observed in OCT images. Elongation of the outer retina could be detected even with brief light exposures, increasing 2.1 +/- 0.3 mu m after 15 minutes (n = 9), and 4.1 +/- 1.0 mu m after 2 hours (n = 6). Conversely, dark-adaptation caused outer retinal shortening of 1.4 +/- 0.4 mu m (n = 7) and 3.0 +/- 0.5 mu m (n = 8) after 15 minutes and 2 hours, respectively. CONCLUSIONS. Light-adaption induces an increase in the thickness of the outer retina and the appearance of a hyporeflective band in the OCT image. This is consistent with previous reports of light-induced fluid accumulation in the subretinal space. C1 [Li, Yichao; Qian, Haohua] NEI, Visual Funct Core, NIH, Bethesda, MD 20892 USA. [Fariss, Robert N.] NEI, Biol Imaging Core, NIH, Bethesda, MD 20892 USA. [Qian, Jennifer W.] Univ Virginia, Coll Arts & Sci, Charlottesville, VA USA. [Cohen, Ethan D.] US FDA, Div Biomed Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Qian, HH (reprint author), NEI, Visual Funct Core, NIH, Bethesda, MD 20892 USA. EM Haohua.qian@nih.gov FU intramural program of the National Eye Institute (Bethesda, MD, USA) FX Supported by the intramural program of the National Eye Institute (Bethesda, MD, USA). The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services. NR 30 TC 0 Z9 0 U1 3 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 JUL PY 2016 VL 57 IS 9 BP OCT105 EP OCT111 DI 10.1167/iovs.15-18539 PG 7 WC Ophthalmology SC Ophthalmology GA DW9MY UT WOS:000383985400002 PM 27409460 ER PT J AU Zeng, Y Petralia, RS Vijayasarathy, C Wu, ZJ Hiriyanna, S Song, HM Wang, YX Sieving, PA Bush, RA AF Zeng, Yong Petralia, Ronald S. Vijayasarathy, Camasamudram Wu, Zhijian Hiriyanna, Suja Song, Hongman Wang, Ya-Xian Sieving, Paul A. Bush, Ronald A. TI Retinal Structure and Gene Therapy Outcome in Retinoschisin-Deficient Mice Assessed by Spectral-Domain Optical Coherence Tomography SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE optical coherence tomography; X-linked retinoschisis; outer nuclear layer; outer retina reflective band; AAV gene therapy ID X-LINKED RETINOSCHISIS; JUVENILE RETINOSCHISIS; MOUSE MODEL; DISEASE PROGRESSION; ADAPTIVE OPTICS; DEGENERATION; CELLS; PHOTORECEPTOR; EXPRESSION; MECHANISMS AB PURPOSE. Spectral-domain optical coherence tomography (SD-OCT) was used to characterize the retinal phenotype, natural history, and treatment responses in a mouse model of X-linked retinoschisis (Rs1-KO) and to identify new structural markers of AAV8-mediated gene therapy outcome. METHODS. Optical coherence tomography scans were performed on wild-type and Rs1-KO mouse retinas between 1 and 12 months of age and on Rs1-KO mice after intravitreal injection of AAV8-scRS/IRBPhRS (AAV8-RS1). Cavities and photoreceptor outer nuclear layer (ONL) thickness were measured, and outer retina reflective band (ORRB) morphology was examined with age and after AAV8-RS1 treatment. Outer retina reflective band morphology was compared to immunohistochemical staining of the outer limiting membrane (OLM) and photoreceptor inner segment (IS) mitochondria and to electron microscopy (EM) images of IS. RESULTS. Retinal cavity size in Rs1-KO mice increased between 1 and 4 months and decreased thereafter, while ONL thickness declined steadily, comparable to previous histologic studies. Wild-type retina had four ORRBs. In Rs1-KO, ORRB1was fragmented from 1 month, but was normal after 8 months; ORRB2 and ORRB3 were merged at all ages. Outer retina reflective band morphology returned to normal after AAV-RS1 therapy, paralleling the recovery of the OLM and IS mitochondria as indicated by anti-beta-catenin and anti-COX4 labeling, respectively, and EM. CONCLUSIONS. Spectral-domain OCT is a sensitive, noninvasive tool to monitor subtle changes in retinal morphology, disease progression, and effects of therapies in mouse models. The ORRBs may be useful to assess the outcome of gene therapy in the treatment of X-linked retinoschisis patients. C1 [Zeng, Yong; Vijayasarathy, Camasamudram; Song, Hongman; Sieving, Paul A.; Bush, Ronald A.] NIDCD, Sect Translat Res Retinal & Macular Degenerat, NIH, Bethesda, MD USA. [Petralia, Ronald S.; Wang, Ya-Xian] NIDCD, Adv Imaging Core, NIH, Bethesda, MD USA. [Wu, Zhijian; Hiriyanna, Suja] NEI, Ocular Gene Therapy Core, NIH, Bethesda, MD 20892 USA. [Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA. RP Bush, RA (reprint author), NIDCD, NIH, 50 South Dr,Room 4339,MSC 8021, Bethesda, MD 20892 USA. EM bushr@nidcd.nih.gov FU Intramural Research Program of the National Institutes of Health, National Institute on Deafness and other Communication Disorders (ZIC) [DC000065-14, DC000081-03]; National Eye Institute FX Supported by the Intramural Research Program of the National Institutes of Health, National Institute on Deafness and other Communication Disorders (ZIC, DC000065-14, DC000081-03), and the National Eye Institute. NR 50 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 JUL PY 2016 VL 57 IS 9 BP OCT277 EP OCT287 DI 10.1167/iovs.15-18920 PG 11 WC Ophthalmology SC Ophthalmology GA DW9MY UT WOS:000383985400026 PM 27409484 ER PT J AU Marks, G Patel, U Stirratt, MJ Mugavero, MJ Mathews, WC Giordano, TP Crepaz, N Gardner, LI Grossman, C Davila, J Sullivan, M Rose, CE O'Daniels, C Rodriguez, A Wawrzyniak, AJ Golden, MR Dhanireddy, S Ellison, J Drainoni, ML Metsch, LR Cachay, ER AF Marks, Gary Patel, Unnati Stirratt, Michael J. Mugavero, Michael J. Mathews, William C. Giordano, Thomas P. Crepaz, Nicole Gardner, Lytt I. Grossman, Cynthia Davila, Jessica Sullivan, Meg Rose, Charles E. O'Daniels, Christine Rodriguez, Allan Wawrzyniak, Andrew J. Golden, Matthew R. Dhanireddy, Shireesha Ellison, Jacqueline Drainoni, Mari-Lynn Metsch, Lisa R. Cachay, Edward R. TI Single Viral Load Measurements Overestimate Stable Viral Suppression Among HIV Patients in Care: Clinical and Public Health Implications SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; viral suppression; viral load; care ID UNITED-STATES; RETENTION; PREVENTION; ATTENDANCE; CONTINUUM; COUNTS; TRENDS AB Background: The HIV continuum of care paradigm uses a single viral load test per patient to estimate the prevalence of viral suppression. We compared this single-value approach with approaches that used multiple viral load tests to examine the stability of suppression. Methods: The retrospective analysis included HIV patients who had at least 2 viral load tests during a 12-month observation period. We assessed the (1) percent with suppressed viral load (<200 copies/mL) based on a single test during observation, (2) percent with suppressed viral loads on all tests during observation, (3) percent who maintained viral suppression among patients whose first observed viral load was suppressed, and (4) change in viral suppression status comparing first with last measurement occasions. Prevalence ratios compared demographic and clinical subgroups. Results: Of 10,942 patients, 78.5% had a suppressed viral load based on a single test, whereas 65.9% were virally suppressed on all tests during observation. Of patients whose first observed viral load was suppressed, 87.5% were suppressed on all subsequent tests in the next 12 months. More patients exhibited improving status (13.3% went from unsuppressed to suppressed) than worsening status (5.6% went from suppressed to unsuppressed). Stable suppression was less likely among women, younger patients, black patients, those recently diagnosed with HIV, and those who missed >= 1 scheduled clinic visits. Conclusions: Using single viral load measurements overestimated the percent of HIV patients with stable suppressed viral load by 16% (relative difference). Targeted clinical interventions are needed to increase the percent of patients with stable suppression. C1 [Marks, Gary; Crepaz, Nicole; Gardner, Lytt I.; Rose, Charles E.] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, 1600 Clifton Ave,MS E-45, Atlanta, GA 30333 USA. [Patel, Unnati] ICF Int, Atlanta, GA USA. [Stirratt, Michael J.; Grossman, Cynthia] NIMH, Div AIDS Res, Bethesda, MD 20892 USA. [Mugavero, Michael J.] Univ Alabama Birmingham, HIV AIDS Clin 1917, Birmingham, AL USA. [Mugavero, Michael J.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Mathews, William C.; Cachay, Edward R.] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Giordano, Thomas P.; Davila, Jessica] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Giordano, Thomas P.; Davila, Jessica] Michael E DeBakey VA Med Ctr, Ctr Innovat Qual Effectiveness & Safety, Houston, TX USA. [Sullivan, Meg] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [O'Daniels, Christine] Carter Consulting Inc, Atlanta, GA USA. [Rodriguez, Allan] Univ Miami, Miller Sch Med, Div Infect Dis, Coral Gables, FL 33124 USA. [Wawrzyniak, Andrew J.] Univ Miami, Miller Sch Med, Psychiat & Behav Sci, Miami, FL 33136 USA. [Golden, Matthew R.] Univ Washington, Ctr AIDS & STD & Publ Health Seattle & King Cty, Seattle, WA 98195 USA. [Dhanireddy, Shireesha] Univ Washington, Dept Med, Seattle, WA USA. [Ellison, Jacqueline; Drainoni, Mari-Lynn] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Metsch, Lisa R.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. RP Marks, G (reprint author), Ctr Dis Control & Prevent, Div HIV AIDS Prevent, 1600 Clifton Ave,MS E-45, Atlanta, GA 30333 USA. EM gmarks@cdc.gov FU NIAID NIH HHS [P30 AI073961] NR 14 TC 0 Z9 0 U1 4 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 OCT 1 PY 2016 VL 73 IS 2 BP 205 EP 212 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA DX1EW UT WOS:000384109800017 PM 27105049 ER PT J AU Guha, R Griner, LAM Keller, JM Zhang, XH Fitzgerald, D Antignani, A Pastan, I Thomas, CJ Ferrer, M AF Guha, Rajarshi Griner, Lesley A. Mathews Keller, Jonathan M. Zhang, Xiaohu Fitzgerald, David Antignani, Antonella Pastan, Ira Thomas, Craig J. Ferrer, Marc TI Ranking Differential Drug Activities from Dose-Response Synthetic Lethality Screens SO JOURNAL OF BIOMOLECULAR SCREENING LA English DT Article DE qHTS; immunotoxin; synthetic lethal screen; ranking ID RECOMBINANT IMMUNOTOXIN; CANCER; DISCOVERY; LEUKEMIA; THERAPY; CELLS; HA22 AB Synthetic lethal screens are used to discover new combination treatments for cancer. In traditional high-throughput synthetic lethal screens, compounds are tested at a single dose, and hit selection is based on threshold activity values from the variance of the efficacy of the compounds tested. The limitation of the single-dose screening for synthetic lethal screens is that it does not allow for the robust detection of differential activities from compound collections with a broad range of potencies and efficacies. There is therefore a need to develop screening approaches that enable the identification of compounds with synthetic lethal effects based on changes in both potency and efficacy. Here we describe the implementation of a dose response-based synthetic lethal screen to find drugs that enhance or mitigate the cytotoxic effect of an immunotoxin protein (HA22). We developed a data analysis framework for the selection of compounds with enhancing or mitigating cytotoxic activities based on the use of dose-response parameters. The data analysis framework includes an ensemble ranking approach that allows the use of multiple dose-response parameters in a nonparametric fashion. Quantitative high-throughput screening (HTS) enables the identification of compounds with synthetic lethal activity not identified by single-dose HTS. C1 [Guha, Rajarshi; Griner, Lesley A. Mathews; Keller, Jonathan M.; Zhang, Xiaohu; Thomas, Craig J.; Ferrer, Marc] NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Rockville, MD USA. [Fitzgerald, David; Antignani, Antonella; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. RP Guha, R; Ferrer, M (reprint author), NCATS, 9800 Med Ctr Dr,Bldg B,Room 3005, Rockville, MD 20850 USA. EM guhar@mail.nih.gov; ferrerm@mail.nih.gov FU National Cancer Institute; National Center for Advancing Translational Sciences FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was funded by the intramural programs of the National Cancer Institute and the National Center for Advancing Translational Sciences. NR 26 TC 0 Z9 0 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0571 EI 1552-454X J9 J BIOMOL SCREEN JI J. Biomol. Screen PD OCT PY 2016 VL 21 IS 9 BP 942 EP 955 DI 10.1177/1087057116644890 PG 14 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry GA DX6CD UT WOS:000384469400007 PM 27112173 ER PT J AU Grabb, MC Cross, AJ Potter, WZ McCracken, JT AF Grabb, Margaret C. Cross, Alan J. Potter, William Z. McCracken, James T. TI Derisking Psychiatric Drug Development The NIMH's Fast Fail Program, A Novel Precompetitive Model SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Editorial Material ID NERVOUS-SYSTEM; AUTISM; PHARMACOLOGY; DISORDERS C1 [Grabb, Margaret C.; Potter, William Z.] NIMH, NIH, 6001 Execut Blvd,Room 7203,MSC 9645, Rockville, MD 20852 USA. [Cross, Alan J.] AstraZeneca Neurosci Innovat Med Unit, Cambridge, MA USA. [McCracken, James T.] UCLA Semel Inst Neurosci, Los Angeles, CA USA. RP Grabb, MC (reprint author), NIMH, NIH, 6001 Execut Blvd,Room 7203,MSC 9645, Rockville, MD 20852 USA. EM mgrabb@mail.nih.gov FU NIMH NIH HHS [HHSN271201200005I] NR 21 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 0271-0749 EI 1533-712X J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD OCT PY 2016 VL 36 IS 5 BP 419 EP 421 DI 10.1097/JCP.0000000000000536 PG 3 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA DX2KD UT WOS:000384197000004 PM 27404513 ER PT J AU Gowans, LJJ Adeyemo, WL Eshete, M Mossey, PA Busch, T Aregbesola, B Donkor, P Arthur, FKN Bello, SA Martinez, A Li, M Augustine-Akpan, EA Deressa, W Twumasi, P Olutayo, J Deribew, M Agbenorku, P Oti, AA Braimah, R Plange-Rhule, G Gesses, M Obiri-Yeboah, S Oseni, GO Olaitan, PB Abdur-Rahman, L Abate, F Hailu, T Gravem, P Ogunlewe, MO Buxo, CJ Marazita, ML Adeyemo, AA Murray, JC Butali, A AF Gowans, L. J. J. Adeyemo, W. L. Eshete, M. Mossey, P. A. Busch, T. Aregbesola, B. Donkor, P. Arthur, F. K. N. Bello, S. A. Martinez, A. Li, M. Augustine-Akpan, E. A. Deressa, W. Twumasi, P. Olutayo, J. Deribew, M. Agbenorku, P. Oti, A. A. Braimah, R. Plange-Rhule, G. Gesses, M. Obiri-Yeboah, S. Oseni, G. O. Olaitan, P. B. Abdur-Rahman, L. Abate, F. Hailu, T. Gravem, P. Ogunlewe, M. O. Buxo, C. J. Marazita, M. L. Adeyemo, A. A. Murray, J. C. Butali, A. TI Association Studies and Direct DNA Sequencing Implicate Genetic Susceptibility Loci in the Etiology of Nonsyndromic Orofacial Clefts in Sub-Saharan African Populations SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE genetic heterogeneity; rare variants; genome-wide association studies (GWAS); candidate genes; craniofacial genetics; population genetics ID GENOME-WIDE ASSOCIATION; IDENTIFIED CANDIDATE GENES; FUNCTIONAL VARIANTS; ORAL CLEFTS; LIP; PALATE; RISK; POLYMORPHISMS; LIP/PALATE; IRF6 AB Orofacial clefts (OFCs) are congenital dysmorphologies of the human face and oral cavity, with a global incidence of 1 per 700 live births. These anomalies exhibit a multifactorial pattern of inheritance, with genetic and environmental factors both playing crucial roles. Many loci have been implicated in the etiology of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in populations of Asian and European ancestries, through genome-wide association studies and candidate gene studies. However, few populations of African descent have been studied to date. Here, the authors show evidence of an association of some loci with NSCL/P and nonsyndromic cleft palate only (NSCPO) in cohorts from Africa (Ghana, Ethiopia, and Nigeria). The authors genotyped 48 single-nucleotide polymorphisms that were selected from previous genome-wide association studies and candidate gene studies. These markers were successfully genotyped on 701 NSCL/P and 163 NSCPO cases, 1,070 unaffected relatives, and 1,078 unrelated controls. The authors also directly sequenced 7 genes in 184 nonsyndromic OFC (NSOFC) cases and 96 controls from Ghana. Population-specific associations were observed in the case-control analyses of the subpopulations, with West African subpopulations (Ghana and Nigeria) showing a similar pattern of associations. In meta-analyses of the case-control cohort, PAX7 (rs742071, P = 5.10 x 10(-3)), 8q24 (rs987525, P = 1.22 x 10(-3)), and VAX1 (rs7078160, P = 0.04) were nominally associated with NSCL/P, and MSX1 (rs115200552, P = 0.01), TULP4 (rs651333, P = 0.04), CRISPLD2 (rs4783099, P = 0.02), and NOG1 (rs17760296, P = 0.04) were nominally associated with NSCPO. Moreover, 7 loci exhibited evidence of threshold overtransmission in NSOFC cases through the transmission disequilibrium test and through analyses of the family-based association for disease traits. Through DNA sequencing, the authors also identified 2 novel, rare, potentially pathogenic variants (p.Asn323Asp and p.Lys426IlefsTer6) in ARHGAP29. In conclusion, the authors have shown evidence for the association of many loci with NSCL/P and NSCPO. To the best of this knowledge, this study is the first to demonstrate any of these association signals in any African population. C1 [Gowans, L. J. J.; Arthur, F. K. N.; Twumasi, P.] Kwame Nkrumah Univ Sci & Technol, Dept Biochem & Biotechnol, Kumasi, Ghana. [Gowans, L. J. J.; Donkor, P.; Agbenorku, P.; Oti, A. A.; Plange-Rhule, G.; Obiri-Yeboah, S.] Komfo Anokye Teaching Hosp, Cleft Clin, Kumasi, Ghana. [Gowans, L. J. J.; Murray, J. C.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. [Gowans, L. J. J.; Busch, T.; Martinez, A.; Li, M.; Augustine-Akpan, E. A.; Butali, A.] Univ Iowa, Dept Oral Pathol Radiol & Med, Iowa City, IA USA. [Adeyemo, W. L.; Olutayo, J.] Univ Lagos, Coll Med, Lagos, Nigeria. [Eshete, M.; Deressa, W.; Deribew, M.] Univ Addis Ababa, Addis Ababa, Ethiopia. [Mossey, P. A.] Univ Dundee, Dept Orthodont, Dundee, Scotland. [Aregbesola, B.; Braimah, R.] Obafemi Awolowo Univ Teaching Hosp, Ife, Nigeria. [Donkor, P.; Agbenorku, P.; Oti, A. A.; Obiri-Yeboah, S.] Kwame Nkrumah Univ Sci & Technol, Sch Med Sci, Dept Surg, Kumasi, Ghana. [Bello, S. A.] State House Hosp, Dept Oral & Maxillofacial Surg, Abuja, Nigeria. [Gesses, M.; Abate, F.; Hailu, T.] Yekatit 12 Hosp, Coll Med, Addis Ababa, Ethiopia. [Oseni, G. O.; Olaitan, P. B.; Ogunlewe, M. O.] Ladoke Akintola Univ Technol, Dept Burns & Plast Surg, Teaching Hosp, Osogbo, Nigeria. [Abdur-Rahman, L.] Univ Ilorin, Dept Surg, Div Pediat Surg, Ilorin, Nigeria. [Gravem, P.] Haukeland Univ Hosp Bergen, Bergen, Norway. [Buxo, C. J.] Univ Puerto Rico Med Sci Campus, Sch Dent Med, San Juan, PR USA. [Marazita, M. L.] Univ Pittsburgh, Dept Oral Biol, Pittsburgh, PA USA. [Adeyemo, A. A.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. RP Butali, A (reprint author), Univ Iowa, Dows Inst Dent Res, Dept Oral Pathol Radiol & Med, Coll Dent,Butali Lab, ML2198,500 Newton Rd, Iowa City, IA 52242 USA. EM azeez-butali@uiowa.edu FU National Institute of Dental and Craniofacial Research [R00 DE022378, R01-DE009886, R01-DE012472, K99-DE024571]; Robert Wood Johnson Foundation [72429]; National Institutes of Health [R37 DE-08559, DE-016148]; Ghana Cleft Foundation; National Institute of Minority Health and Disparities [U54-MD007587, R25-MD007607] FX The authors are grateful to all families that participated in this research. We also appreciate all the doctors and nurses at the various teaching hospitals where sample collections were carried out: Komfo Anokye Teaching Hospital (Ghana), University of Lagos Teaching Hospital (Nigeria), Obafemi Awolowo University Teaching Hospital (Nigeria), Ladoke Akintola University of Technology Teaching Hospital (Nigeria), and Yekatit 12 Hospital Medical college (Ethiopia). Contributions of members of the Murray and Butali laboratories, University of Iowa, are acknowledged. This work was supported by the National Institute of Dental and Craniofacial Research (R00 DE022378) and the Robert Wood Johnson Foundation (72429; A.B.); the National Institutes of Health (R37 DE-08559 and DE-016148; J.C.M.); the Ghana Cleft Foundation (L.J.J.G.); the National Institute of Dental and Craniofacial Research (R01-DE009886 and R01-DE012472; M.L.M.); and the National Institute of Minority Health and Disparities (U54-MD007587, R25-MD007607; C.J.B.) and the National Institute of Dental and Craniofacial Research (K99-DE024571; C.J.B.). The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 38 TC 1 Z9 1 U1 4 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 EI 1544-0591 J9 J DENT RES JI J. Dent. Res. PD OCT PY 2016 VL 95 IS 11 BP 1245 EP 1256 DI 10.1177/0022034516657003 PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DX5XU UT WOS:000384456800007 PM 27369588 ER PT J AU Chu, EY Tamasas, B Fong, H Foster, BL LaCourse, MR Tran, AB Martin, JF Schutte, BC Somerman, MJ Cox, TC AF Chu, E. Y. Tamasas, B. Fong, H. Foster, B. L. LaCourse, M. R. Tran, A. B. Martin, J. F. Schutte, B. C. Somerman, M. J. Cox, T. C. TI Full Spectrum of Postnatal Tooth Phenotypes in a Novel Irf6 Cleft Lip Model SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE amelogenesis; hypodontia; supernumerary teeth; van der Woude; cleft lip; palate; taurodontism ID DER-WOUDE-SYNDROME; REGULATORY FACTOR 6; ENAMEL DEFECTS; DENTAL ANOMALIES; CAUSE VAN; PALATE; CHILDREN; GENE; MORPHOGENESIS; EXPRESSION AB Clefting of the lip, with or without palatal involvement (CLP), is associated with a higher incidence of developmental tooth abnormalities, including hypodontia and supernumerary teeth, aberrant crown and root morphologies, and enamel defects, although the underlying mechanistic link is poorly understood. As most CLP genes are expressed throughout the oral epithelium, the authors hypothesized that the expression of CLP genes may persist in the dental epithelium and thus, in addition to their earlier role in labiopalatine development, may play an important functional role in subsequent tooth patterning and amelogenesis. To address this, the authors generated a unique conditional knockout model involving the major CLP gene, Irf6, that overcomes the previously reported perinatal lethality to enable assessment of any posteruption dental phenotypes. A dental epithelium-specific Irf6 conditional knockout (Irf6-cKO) mouse was generated via a Pitx2-Cre driver line. Dental development was analyzed by microcomputed tomography, scanning electron microscopy, histology, immunohistochemistry, and quantitative polymerase chain reaction. Irf6-cKO mice displayed variable hypodontia, occasional supernumerary incisors and molars, as well as crown and root patterning anomalies, including peg-shaped first molars and taurodontic and C-shaped mandibular second molars. Enamel density was reduced in preeruption Irf6-cKO mice, and some shearing of enamel rods was noted in posteruption incisors. There was also rapid attrition of Irf6-cKO molars following eruption. Histologically, Irf6-cKO ameloblasts exhibited disturbances in adhesion and polarity, and delayed enamel formation was confirmed immunohistochemically. Altered structure of Hertwig's epithelial root sheath was also observed. These data support a role for IRF6 in tooth number, crown and root morphology and amelogenesis that is likely due to a functional role of Irf6 in organization and polarity of epithelial cell types. This data reinforce the notion that various isolated tooth defects could be considered part of the CLP spectrum in relatives of an affected individual. C1 [Chu, E. Y.; Tamasas, B.] Univ Washington, Dept Oral Hlth Sci, Seattle, WA 98195 USA. [Chu, E. Y.; Tamasas, B.; LaCourse, M. R.; Cox, T. C.] Seattle Childrens Res Inst, Ctr Dev Biol & Regenerat Med, Seattle, WA USA. [Chu, E. Y.; Tran, A. B.; Somerman, M. J.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Fong, H.] Univ Washington, Dept Mat Sci & Engn, Seattle, WA 98195 USA. [Foster, B. L.] Ohio State Univ, Coll Dent, Biosci Div, Columbus, OH 43210 USA. [Martin, J. F.] Baylor Coll Med, Dept Mol Physiol & Biophys, Houston, TX 77030 USA. [Martin, J. F.] Texas Heart Inst, Houston, TX 77025 USA. [Schutte, B. C.] Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA. [Cox, T. C.] Univ Washington, Dept Pediat, Div Craniofacial Med, Seattle, WA 98195 USA. [Cox, T. C.] Monash Univ, Dept Anat & Dev Biol, Clayton, Vic, Australia. RP Cox, TC (reprint author), Seattle Childrens Res Inst, Ctr Dev Biol & Regenerat Med, M-S C9S-5,1900 Ninth Ave, Seattle, WA 98101 USA. EM tccox@uw.edu FU Laurel Foundation Endowment for Craniofacial Research; University of Washington National Institute of Dental and Craniofacial Research T32 Institutional Trainee Award [DE007132]; National Institute of Diabetes and Digestive and Kidney Diseases Ruth L. Kirschstein F30 fellowship [DK100280]; National Institutes of Health [DE023177]; Cleft Palate Foundation Junior Investigator Research Grant; Libyan Government scholarship; Internal Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health FX This research was supported in part by the Laurel Foundation Endowment for Craniofacial Research (T.C.C.), a University of Washington National Institute of Dental and Craniofacial Research T32 Institutional Trainee Award (DE007132; E.Y.C.), an National Institute of Diabetes and Digestive and Kidney Diseases Ruth L. Kirschstein F30 fellowship (DK100280; E.Y.C.), National Institutes of Health DE023177 (J.F.M.), a Cleft Palate Foundation Junior Investigator Research Grant (E.Y.C.), a Libyan Government scholarship (B.T.), and the Internal Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (M.J.S.). The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. The authors thank members of the Somerman and Cox laboratories for their support and Thuy Tien Tran (Baylor College of Medicine) and Youssef Kousa (Michigan State University) for providing assistance with genotyping. Additionally, the authors thank the Light Imaging Core Facility (National Institute of Arthritis and Musculoskeletal and Skin Diseases / National Institutes of Health), James Schmitz (University of Texas Health Sciences Center at San Antonio), Dr. Yong-Hee Chun (University of Texas Health Science Center at San Antonio), and Drs. Daniel Chan, Michael Cunningham, Tracy Popowics, and Avina Paranjpe (University of Washington) for their support and advice. NR 40 TC 4 Z9 4 U1 5 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 EI 1544-0591 J9 J DENT RES JI J. Dent. Res. PD OCT PY 2016 VL 95 IS 11 BP 1265 EP 1273 DI 10.1177/0022034516656787 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DX5XU UT WOS:000384456800009 PM 27369589 ER PT J AU Doyle, DL Awwad, RI Austin, JC Baty, BJ Bergner, AL Brewster, SJ Erby, LAH Franklin, CR Greb, AE Grubs, RE Hooker, GW Noblin, SJ Ormond, KE Palmer, CG Petty, EM Singletary, CN Thomas, MJ Toriello, H Walton, CS Uhlmann, WR AF Doyle, Debra Lochner Awwad, Rawan I. Austin, Jehannine C. Baty, Bonnie J. Bergner, Amanda L. Brewster, Stephanie J. Erby, Lori A. H. Franklin, Cathi Rubin Greb, Anne E. Grubs, Robin E. Hooker, Gillian W. Noblin, Sarah Jane Ormond, Kelly E. Palmer, Christina G. Petty, Elizabeth M. Singletary, Claire N. Thomas, Matthew J. Toriello, Helga Walton, Carol S. Uhlmann, Wendy R. TI 2013 Review and Update of the Genetic Counseling Practice Based Competencies by a Task Force of the Accreditation Council for Genetic Counseling SO JOURNAL OF GENETIC COUNSELING LA English DT Review DE Genetic counseling; Practice based competencies (PBCs); Graduate program accreditation; Genetic counselors; Training; Curriculum AB The first practice based competencies (PBCs) for the field of genetic counseling were adopted by the American Board of Genetic Counseling (ABGC), 1996. Since that time, there has been significant growth in established and new work settings (clinical and non-clinical) and changes in service delivery models and the roles of genetic counselors. These changes prompted the ABGC to appoint a PBC Task Force in 2011 to review the PBCs with respect to their current relevance and to revise and update them as necessary. There are four domains in the revised PBCs: (I) Genetics Expertise and Analysis (II) Interpersonal, Psychosocial and Counseling Skills (III) Education and (IV) Professional Development and Practice. There are 22 competencies, each clarified with learning objectives or samples of activities and skills; a glossary is included. New competencies were added that address genomics, genetic testing and genetic counselors' roles in risk assessment, education, supervision, conducting research and presenting research options to patients. With PBCs serving as the pre-defined abilities or outcomes of training, graduating genetic counselors will be well prepared to enter the field with a minimum level of skills and abilities. A description of the Task Force's work, key changes and the 2013 PBCs are presented herein. C1 [Doyle, Debra Lochner] Washington State Dept Hlth, Screening & Genet Unit, 20425 72nd Ave S,Suite 310, Kent, WA 98032 USA. [Awwad, Rawan I.] Counsyl Inc, San Francisco, CA USA. [Austin, Jehannine C.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. [Austin, Jehannine C.] Univ British Columbia, Dept Psychiat, Vancouver, BC, Canada. [Baty, Bonnie J.] Univ Utah, Dept Pediat, Salt Lake City, UT USA. [Bergner, Amanda L.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD USA. [Brewster, Stephanie J.] Boston Childrens Hosp, Translat Neurosci Ctr, Boston, MA USA. [Erby, Lori A. H.] Johns Hopkins Bloomberg Sch Publ Hlth, Hlth Behav & Soc, Baltimore, MD USA. [Erby, Lori A. H.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. [Franklin, Cathi Rubin] Quest Diagnost Inc, Valencia, CA USA. [Greb, Anne E.] Sarah Lawrence Coll, Joan H Marks Grad Program Human Genet, Bronxville, NY 10708 USA. [Grubs, Robin E.] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. [Hooker, Gillian W.] NextGxDx Inc, Franklin, TN USA. [Noblin, Sarah Jane] Univ Texas Hlth Sci Ctr Houston, Dept Obstet Gynecol & Reprod Serv, Houston, TX 77030 USA. [Noblin, Sarah Jane] Univ Texas Hlth Sci Ctr Houston, Dept Pediat, Houston, TX 77030 USA. [Ormond, Kelly E.] Stanford Univ, Sch Med, Dept Genet, Stanford, CA USA. [Palmer, Christina G.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Petty, Elizabeth M.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pediat, Madison, WI USA. [Singletary, Claire N.] Univ Texas Hlth Sci Ctr Houston, Dept Pediat & Obstet Gynecol & Reprod Serv, Houston, TX 77030 USA. [Thomas, Matthew J.] Univ Virginia Hlth Syst, Dept Pediat, Charlottesville, VA USA. [Toriello, Helga] Spectrum Hlth, Grand Rapids, MI USA. [Walton, Carol S.] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO USA. [Uhlmann, Wendy R.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Uhlmann, Wendy R.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. RP Doyle, DL (reprint author), Washington State Dept Hlth, Screening & Genet Unit, 20425 72nd Ave S,Suite 310, Kent, WA 98032 USA. EM debra.lochnerdoyle@doh.wa.gov FU ABGC FX While all PBCTF members volunteered their time, funds to support their travel were provided by the ABGC. In addition, the authors would like to offer their heartfelt appreciation to Morry Fiddler, PhD for his thoughtful review of our article and sharing his expertise in describing the processes used to develop competencies. We also wish to thank the AGCPD for their thoughtful review of comments offered regarding draft versions of the PBCs, and express our gratitude to the ACGC Executive Director, Sheila O'Neal, for her support in developing the final PBC document and posting it to the ACGC website at: http://gceducation.org/Documents/ACGC%20Core%20Competencies%20Brochure_1 4_Web_FINAL.pdf NR 12 TC 0 Z9 1 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1059-7700 EI 1573-3599 J9 J GENET COUNS JI J. Genet. Couns. PD OCT PY 2016 VL 25 IS 5 BP 868 EP 879 DI 10.1007/s10897-016-9984-3 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA DX4EB UT WOS:000384332900003 PM 27333894 ER PT J AU Nakamura, T Campbell, JR Moore, AR Otsu, S Aikawa, H Tamamura, H Mitsuya, H AF Nakamura, Tomofumi Campbell, Joseph R. Moore, Amber R. Otsu, Sachiko Aikawa, Haruo Tamamura, Hirokazu Mitsuya, Hiroaki TI Development and validation of a cell-based assay system to assess human immunodeficiency virus type 1 integrase multimerization SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE HIV-1; HIV-1 integrase multimerization; BiFC; NCINIs ID THROUGHPUT SCREENING ASSAYS; SMALL-MOLECULE INHIBITORS; DNA STRAND TRANSFER; HIV-1 INTEGRASE; VIRAL-DNA; IN-VIVO; FLUORESCENCE COMPLEMENTATION; BINDING-SITE; PROTEIN; EXPRESSION AB Multimerization of HIV-1 integrase (IN) subunits is required for the concerted integration of HIV-1 proviral DNA into the host genome. Thus, the disruption of IN multimerization represents a new avenue for intervening HIV-1 infection. Here, we generated a cell-based assay system to assess IN multimerization using a newly constructed bimolecular fluorescence complementation (BiFC-IN) system. BiFC-IN proteins were efficient in emitting fluorescence, and amino acid (AA) substitutions associated with IN multimerization attenuated fluorescence, suggesting that the BiFC-IN system may be useful for evaluating the profile of IN multimerization. A recently reported non-catalytic site IN inhibitor (NCINI), which allosterically induces IN over-multimerization/aggregation, significantly increased fluorescence in the BiFC-IN system. An IN's substitution, A128T, associated with viral resistance to NCINIs, decreased the NCINI-induced increase of fluorescence, suggesting that A128T reduces the potential for IN over-multimerization. Moreover, E11K and F181T substitutions known to inhibit IN tetramerization also reduced the NCINI-induced fluorescence increase, suggesting that NCINI-induced IN over-multimerization was more likely to occur from tetramer subunits than from dimer subunits. The present study demonstrates that our cell-based BiFC-IN system may be useful in elucidating the profile of IN multimerization, and also help evaluate and identify novel compounds that disrupt IN multimerization in living cells. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license. C1 [Nakamura, Tomofumi; Campbell, Joseph R.; Moore, Amber R.; Otsu, Sachiko; Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med Sci, Dept Infect Dis, Kumamoto 8608556, Japan. [Nakamura, Tomofumi; Campbell, Joseph R.; Moore, Amber R.; Otsu, Sachiko; Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med Sci, Dept Hematol, Kumamoto 8608556, Japan. [Aikawa, Haruo; Tamamura, Hirokazu] Tokyo Med & Dent Univ, Inst Biomat & Bioengn, Chiyoda Ku, Tokyo 1010062, Japan. [Mitsuya, Hiroaki] Natl Ctr Global Hlth & Med Res Inst, Expt Retrovirol Sect, Shinjuku Ku, Tokyo 1628655, Japan. [Mitsuya, Hiroaki] NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. RP Mitsuya, H (reprint author), Kumamoto Univ, Grad Sch Med Sci, Dept Infect Dis, Kumamoto 8608556, Japan.; Mitsuya, H (reprint author), Kumamoto Univ, Grad Sch Med Sci, Dept Hematol, Kumamoto 8608556, Japan.; Mitsuya, H (reprint author), Natl Ctr Global Hlth & Med Res Inst, Expt Retrovirol Sect, Shinjuku Ku, Tokyo 1628655, Japan.; Mitsuya, H (reprint author), NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. EM mitsuyah@helix.nih.gov FU Japan Agency for Medical Research and Development (AMED); Grant for global education and research center aiming at the control of AIDS (Global Center of Excellence - Monbu-Kagakusho); Promotion of AIDS Research from the Ministry of Health, Welfare, and Labor of Japan; Kumamoto University [78]; Monbu-Kagakusho [21790527]; Intramural Research Program of Center for Cancer Research, National Cancer Institute, National Institutes of Health FX We thank Gene Technology, Center Institute of Resource Development and Analysis, Kumamoto University for providing technical supports of FCM and confocal lazer scanning microscope. We also thank Toshikazu Miyagawa, Masayuki Amano, and Hironori Hayashi for helpful discussion, and Miho Matsumoto for technical assistance. This work was supported in part by a Grant for Development of Novel Drugs for Treating HIV-1 Infection and AIDS from Japan Agency for Medical Research and Development (AMED), by a Grant for global education and research center aiming at the control of AIDS (Global Center of Excellence supported by Monbu-Kagakusho), a Promotion of AIDS Research from the Ministry of Health, Welfare, and Labor of Japan, a Grant to the Cooperative Research Project on Clinical and Epidemiological Studies of Emerging and Re-emerging Infectious Diseases (Renkei Jigyo: No. 78, Kumamoto University) of Monbu-Kagakusho, and a Grant-in-Aid for Young Scientists (B) (21790527) of Monbu-Kagakusho, and in part by the Intramural Research Program of Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 60 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 EI 1879-0984 J9 J VIROL METHODS JI J. Virol. Methods PD OCT PY 2016 VL 236 BP 196 EP 206 DI 10.1016/j.jviromet.2016.07.023 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA DW8YR UT WOS:000383941900029 PM 27474494 ER PT J AU Limou, S Parsa, A AF Limou, Sophie Parsa, Afshin TI Diving into the abyss of undiscovered kidney function-related factors SO KIDNEY INTERNATIONAL LA English DT Editorial Material ID LOCI AB Meta-analyses and reintroduction of biological knowledge are 2 classic strategies to increase genomewide association study statistical power and overcome the burden of multiple testing. These strategies have empowered the nephrology community to discover new signals associated with kidney function and nephropathies: Here we discuss the current genomewide association study limitations and strategies to dive further into the abyss of yet-to-be discovered kidney function-related factors. C1 [Limou, Sophie] NCI, Mol Genet Epidemiol Sect, Basic Res Lab, Basic Sci Program,Leidos Biomed Res Inc,Frederick, Frederick, MD 21701 USA. [Parsa, Afshin] Univ Maryland, Sch Med, Div Nephrol, Baltimore, MD 21201 USA. [Parsa, Afshin] Baltimore VA Med Ctr, Dept Med, Baltimore, MD USA. RP Parsa, A (reprint author), Univ Maryland, Sch Med, 685 W Baltimore St,MSTF 357, Baltimore, MD 21201 USA. EM aparsa@medicine.umaryland.edu NR 9 TC 1 Z9 1 U1 2 U2 2 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 OCT PY 2016 VL 90 IS 4 BP 724 EP 726 DI 10.1016/j.kint.2016.05.034 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA DX4ZE UT WOS:000384388800003 PM 27633863 ER PT J AU Jing, JJ Pattaro, C Hoppmann, A Okada, Y Fox, CS Kottgen, A AF Jing, Jiaojiao Pattaro, Cristian Hoppmann, Anselm Okada, Yukinori Fox, Caroline S. Koettgen, Anna CA CKDGen Consortium TI Combination of mouse models and genomewide association studies highlights novel genes associated with human kidney function SO KIDNEY INTERNATIONAL LA English DT Article DE chronic kidney disease; genomewide association studies; kidney development ID GLOMERULAR-FILTRATION-RATE; WIDE ASSOCIATION; COLLABORATIVE METAANALYSIS; POPULATION COHORTS; RETINOIC ACID; HIGHER ALBUMINURIA; EMBRYONIC KIDNEY; HUMAN BIOLOGY; DISEASE; BONE AB Genomewide association studies have identified numerous chronic kidney disease-associated genetic variants, but often do not pinpoint causal genes. This limitation was addressed by combining Mouse Genome Informatics with human genomewide association studies of kidney function. Genes for which mouse models showed abnormal renal physiology, morphology, glomerular filtration rate (GFR), or urinary albumin-to-creatinine ratio were identified from Mouse Genome Informatics. The corresponding human orthologs were then evaluated for GFR-associated single-nucleotide polymorphisms in 133,814 individuals and urinary albumin-to-creatinine ratio-associated SNPs in 54,451 individuals in genome-wide association studies meta-analysis of the CKDGen Consortium. After multiple testing corrections, significant associations with estimated GFR in humans were identified for single-nucleotide polymorphisms in 2, 7, and 17 genes causing abnormal GFR, abnormal physiology, and abnormal morphology in mice, respectively. Genes identified for abnormal kidney morphology showed significant enrichment for estimated GFR-associated single-nucleotide polymorphisms. In total, 19 genes contained variants associated with estimated GFR or the urinary albumin-to-creatinine ratio of which 16 mapped into previously reported genomewide significant loci. CYP26A1 and BMP4 emerged as novel signals subsequently validated in a large, independent study. An additional gene, CYP24A1, was discovered after conditioning on a published nearby association signal. Thus, our novel approach to combine comprehensive mouse phenotype information with human genomewide association studies data resulted in the identification of candidate genes for kidney disease pathogenesis. C1 [Jing, Jiaojiao; Hoppmann, Anselm; Koettgen, Anna] Univ Freiburg, Div Genet Epidemiol, Med Ctr, Freiburg, Germany. [Jing, Jiaojiao; Hoppmann, Anselm] Univ Freiburg, Genet & Expt Bioinformat, Fac Biol, Freiburg, Germany. [Jing, Jiaojiao; Koettgen, Anna] Univ Freiburg, Div Renal, Med Ctr, Freiburg, Germany. [Pattaro, Cristian] European Acad Bolzano Bozen EURAC, Ctr Biomed, Bolzano, Italy. [Okada, Yukinori] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Human Genet & Dis Divers, Tokyo, Japan. [Okada, Yukinori] RIKEN, Lab Stat Anal, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] NHLBI, Ctr Populat Studies, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Metab & Hypertens, 75 Francis St, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Med Sch, Boston, MA USA. [Koettgen, Anna] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Kottgen, A (reprint author), Univ Freiburg, Med Ctr, Berliner Allee 29, D-79110 Freiburg, Germany. EM anna.koettgen@uniklinik-freiburg.de FU Emmy Noether Programme; Heisenberg Programme; German Research Foundation [CRC 1140]; Chinese Scholarship Council; Wellcome Trust [076113, 085475] FX The work of AK was funded by the Emmy Noether Programme, the Heisenberg Programme, and CRC 1140 of the German Research Foundation. JJ was funded by the Chinese Scholarship Council. This study makes use of data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the generation of the data is available at www.wtccc.org.uk. Funding for the project was provided by the Wellcome Trust under award 076113 and 085475. We thank Vladan Mijatovic for helpful discussions. NR 54 TC 2 Z9 2 U1 1 U2 1 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 OCT PY 2016 VL 90 IS 4 BP 764 EP 773 DI 10.1016/j.kint.2016.04.004 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA DX4ZE UT WOS:000384388800012 PM 27263491 ER PT J AU Kasiske, BL Kumar, R Kimmel, PL Pesavento, TE Kalil, RS Kraus, ES Rabb, H Posselt, AM Anderson-Haag, TL Steffes, MW Israni, AK Snyder, JJ Singh, RJ Weir, MR AF Kasiske, Bertram L. Kumar, Rajiv Kimmel, Paul L. Pesavento, Todd E. Kalil, Roberto S. Kraus, Edward S. Rabb, Hamid Posselt, Andrew M. Anderson-Haag, Teresa L. Steffes, Michael W. Israni, Ajay K. Snyder, Jon J. Singh, Ravinder J. Weir, Matthew R. TI Abnormalities in biomarkers of mineral and bone metabolism in kidney donors SO KIDNEY INTERNATIONAL LA English DT Article DE FGF23; hyperparathyroidism; mineral metabolism; parathyroid hormone ID FIBROBLAST GROWTH FACTOR-23; UNILATERAL NEPHRECTOMY; FOLLOW-UP; CARDIOVASCULAR-DISEASE; PARATHYROID-HORMONE; PHOSPHATE-TRANSPORT; MATCHED COHORT; VITAMIN-D; DONATION; FGF-23 AB Previous studies have suggested that kidney donors may have abnormalities of mineral and bone metabolism typically seen in chronic kidney disease. This may have important implications for the skeletal health of living kidney donors and for our understanding of the pathogenesis of long-term mineral and bone disorders in chronic kidney disease. In this prospective study, 182 of 203 kidney donors' and 173 of 201 paired normal controls had markers of mineral and bone metabolism measured before and at 6 and 36 months after donation (ALTOLD Study). Donors had significantly higher serum concentrations of intact parathyroid hormone (24.6% and 19.5%) and fibroblast growth factor-23 (9.5% and 8.4%) at 6 and 36 months, respectively, as compared to healthy controls, and significantly reduced tubular phosphate reabsorption (-7.0% and -5.0%) and serum phosphate concentrations (-6.4% and -2.3%). Serum 1,25-dihydroxyvitamin D-3 concentrations were significantly lower (-17.1% and -12.6%), while 25-hydroxyvitamin D (21.4% and 19.4%) concentrations were significantly higher in donors compared to controls. Moreover, significantly higher concentrations of the bone resorption markers, carboxyterminal cross-linking telopeptide of bone collagen (30.1% and 13.8%) and aminoterminal cross-linking telopeptide of bone collagen (14.2% and 13.0%), and the bone formation markers, osteocalcin (26.3% and 2.7%) and procollagen type I N-terminal propeptide (24.3% and 8.9%), were observed in donors. Thus, kidney donation alters serum markers of bone metabolism that could reflect impaired bone health. Additional long-term studies that include assessment of skeletal architecture and integrity are warranted in kidney donors. C1 [Kasiske, Bertram L.; Anderson-Haag, Teresa L.; Israni, Ajay K.] Hennepin Cty Med Ctr, Dept Med, 701 Pk Ave, Minneapolis, MN 55415 USA. [Kumar, Rajiv] Mayo Clin, Dept Med, Rochester, MN USA. [Kimmel, Paul L.] NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. [Pesavento, Todd E.] Ohio State Univ, Dept Med, Columbus, OH 43210 USA. [Kalil, Roberto S.] Univ Iowa, Dept Med, Iowa City, IA 52242 USA. [Kraus, Edward S.; Rabb, Hamid] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Posselt, Andrew M.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Steffes, Michael W.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Israni, Ajay K.; Snyder, Jon J.] Minneapolis Med Res Fdn Inc, Minneapolis, MN USA. [Singh, Ravinder J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Weir, Matthew R.] Univ Maryland, Dept Med, Baltimore, MD 21201 USA. RP Kasiske, BL (reprint author), Hennepin Cty Med Ctr, Dept Med, 701 Pk Ave, Minneapolis, MN 55415 USA.; Kumar, R (reprint author), Mayo Clin, MS 1-120,200 First St SW, Rochester, MN 55905 USA. EM bkasiske@cdrg.org; rkumar@mayo.edu FU National Institutes of Health [U01-DK066013] FX This study was funded by the National Institutes of Health under the cooperative agreement U01-DK066013. The National Institutes of Health participated in the interpretation of data, the writing of the report, and the decision to submit the report for publication. The opinions expressed herein do not necessarily reflect those of the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, the Department of Health and Human Services, or the government of the United States. NR 33 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD OCT PY 2016 VL 90 IS 4 BP 861 EP 868 DI 10.1016/j.kint.2016.05.012 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA DX4ZE UT WOS:000384388800022 ER PT J AU Fallah, MP Skrip, LA Dahn, BT Nyenswah, TG Flumo, H Glayweon, M Lorseh, TL Kaler, SG Higgs, ES Galvani, AP AF Fallah, Mosoka P. Skrip, Laura A. Dahn, Bernice T. Nyenswah, Tolbert G. Flumo, Hilary Glayweon, Meekie Lorseh, Tee L. Kaler, Stephen G. Higgs, Elizabeth S. Galvani, Alison P. TI Pregnancy outcomes in Liberian women who conceived after recovery from Ebola virus disease SO LANCET GLOBAL HEALTH LA English DT Editorial Material C1 [Fallah, Mosoka P.; Dahn, Bernice T.; Nyenswah, Tolbert G.; Glayweon, Meekie; Lorseh, Tee L.] Minist Hlth, Monrovia, Liberia. [Fallah, Mosoka P.; Galvani, Alison P.] Univ Liberia, AM Dogliotti Coll Med, Monrovia, Liberia. [Fallah, Mosoka P.; Flumo, Hilary] PREVAIL III Study, US Natl Inst Allergy & Infect Dis, Monrovia, Liberia. [Skrip, Laura A.; Galvani, Alison P.] Yale Sch Publ Hlth, Ctr Infect Dis Modeling & Anal, New Haven, CT 06510 USA. [Kaler, Stephen G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Translat Neurosci, Mol Med Branch, NIH, Bethesda, MD USA. [Higgs, Elizabeth S.] NIAID, US Natl Inst Hlth, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Galvani, AP (reprint author), Univ Liberia, AM Dogliotti Coll Med, Monrovia, Liberia.; Galvani, AP (reprint author), Yale Sch Publ Hlth, Ctr Infect Dis Modeling & Anal, New Haven, CT 06510 USA. EM alison.galvani@yale.edu NR 10 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2214-109X J9 LANCET GLOB HEALTH JI Lancet Glob. Health PD OCT PY 2016 VL 4 IS 10 BP E678 EP E679 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DW7RE UT WOS:000383848000009 PM 27633422 ER PT J AU Mokdad, AH Forouzanfar, MH Daoud, F El Bcheraoui, C Moradi-Lakeh, M Khalil, I Afshin, A Tuffaha, M Charara, R Barber, RM Wagner, J Cercy, K Kravitz, H Coates, MM Robinson, M Estep, K Steiner, C Jaber, S Mokdad, AA O'Rourke, KF Chew, A Kim, P El Razek, MMA Abdalla, S Abd-Allah, F Abraham, JP Abu-Raddad, LJ Abu-Rmeileh, NME Al-Nehmi, AA Akanda, AS Al Ahmadi, H Al Khabouri, MJ Al Lami, FH Al Rayess, ZA Alasfoor, D AlBuhairan, FS Aldhahri, SF Alghnam, S Alhabib, S Al-Hamad, N Ali, R Ali, SD Alkhateeb, M AlMazroa, MA Alomari, MA Al-Raddadi, R Alsharif, U Al-Sheyab, N Alsowaidi, S Al-Thani, M Altirkawi, KA Amare, AT Amini, H Ammar, W Anwari, P Asayesh, H Asghar, R Assabri, AM Assadi, R Bacha, U Badawi, A Bakfalouni, T Basulaiman, MO Bazargan-Hejazi, S Bedi, N Bhakta, AR Bhutta, ZA Bin Abdulhak, AA Boufous, S Bourne, RRA Danawi, H Das, J Deribew, A Ding, EL Durrani, AM Elshrek, Y Ibrahim, ME Eshrati, B Esteghamati, A Faghmous, IAD Farzadfar, F Feigl, AB Fereshtehnejad, SM Filip, I Fischer, F Gankpe, FG Ginawi, I Gishu, MD Gupta, R Habash, RM Hafezi-Nejad, N Hamadeh, RR Hamdouni, H Hamidi, S Harb, HL Hassanvand, MS Hedayati, MT Heydarpour, P Hsairi, M Husseini, A Jahanmehr, N Jha, V Jonas, JB Karam, NE Kasaeian, A Kassa, NA Kaul, A Khader, Y Khalifa, SEA Khan, EA Khan, G Khoja, TK Khosravi, A Kinfu, Y Defo, BK Balaji, AL Lunevicius, R Obermeyer, CM Malekzadeh, R Mansourian, M Marcenes, W Farid, HM Mehari, A Memish, ZA Mehio-Sibai, A Memish, ZA Mensah, GA Mohammad, KA Nahas, Z Nasher, JT Nawaz, H Nejjari, C Nisar, MI Omer, SB Parsaeian, M Peprah, EK Pervaiz, A Pourmalek, F Qato, DM Qorbani, M Radfar, A Rafay, A Rahimi, K Rahimi-Movaghar, V Rahman, SU Rai, RK Rana, SM Rao, SR Refaat, AH Resnikoff, S Roshandel, G Saade, G Saeedi, MY Sahraian, MA Saleh, S Sanchez-Riera, L Satpathy, M Sepanlou, SG Setegn, T Shaheen, A Shahraz, S Sheikhbahaei, S Shishani, K Sliwa, K Tavakkoli, M Terkawi, AS Uthman, OA Westerman, R Younis, MZ Zaki, MES Zannad, F Roth, GA Wang, HD Naghavi, M Vos, T Al Rabeeah, AA Lopez, AD Murray, CJL AF Mokdad, Ali H. Forouzanfar, Mohammad Hossein Daoud, Farah El Bcheraoui, Charbel Moradi-Lakeh, Maziar Khalil, Ibrahim Afshin, Ashkan Tuffaha, Marwa Charara, Raghid Barber, Ryan M. Wagner, Joseph Cercy, Kelly Kravitz, Hannah Coates, Matthew M. Robinson, Margaret Estep, Kara Steiner, Caitlyn Jaber, Sara Mokdad, Ali A. O'Rourke, Kevin F. Chew, Adrienne Kim, Pauline El Razek, Mohamed Magdy Abd Abdalla, Safa Abd-Allah, Foad Abraham, Jerry P. Abu-Raddad, Laith J. Abu-Rmeileh, Niveen M. E. Al-Nehmi, Abdulwahab A. Akanda, Ali S. Al Ahmadi, Hanan Al Khabouri, Mazin J. Al Lami, Faris H. Al Rayess, Zulfa A. Alasfoor, Deena AlBuhairan, Fadia S. Aldhahri, Saleh F. Alghnam, Suliman Alhabib, Samia Al-Hamad, Nawal Ali, Raghib Ali, Syed Danish Alkhateeb, Mohammad AlMazroa, Mohammad A. Alomari, Mahmoud A. Al-Raddadi, Rajaa Alsharif, Ubai Al-Sheyab, Nihaya Alsowaidi, Shirina Al-Thani, Mohamed Altirkawi, Khalid A. Amare, Azmeraw T. Amini, Heresh Ammar, Walid Anwari, Palwasha Asayesh, Hamid Asghar, Rana Assabri, Ali M. Assadi, Reza Bacha, Umar Badawi, Alaa Bakfalouni, Talal Basulaiman, Mohammed O. Bazargan-Hejazi, Shahrzad Bedi, Neeraj Bhakta, Amit R. Bhutta, Zulfiqar A. Bin Abdulhak, Aref A. Boufous, Soufiane Bourne, Rupert R. A. Danawi, Hadi Das, Jai Deribew, Amare Ding, Eric L. Durrani, Adnan M. Elshrek, Yousef Ibrahim, Mohamed E. Eshrati, Babak Esteghamati, Alireza Faghmous, Imad A. D. Farzadfar, Farshad Feigl, Andrea B. Fereshtehnejad, Seyed-Mohammad Filip, Irina Fischer, Florian Gankpe, Fortune G. Ginawi, Ibrahim Gishu, Melkamu Dedefo Gupta, Rahul Habash, Rami M. Hafezi-Nejad, Nima Hamadeh, Randah R. Hamdouni, Hayet Hamidi, Samer Harb, Hilda L. Hassanvand, Mohammad Sadegh Hedayati, Mohammad T. Heydarpour, Pouria Hsairi, Mohamed Husseini, Abdullatif Jahanmehr, Nader Jha, Vivekanand Jonas, Jost B. Karam, Nadim E. Kasaeian, Amir Kassa, Nega Assefa Kaul, Anil Khader, Yousef Khalifa, Shams Eldin A. Khan, Ejaz A. Khan, Gulfaraz Khoja, Tawfi K. Khosravi, Ardeshir Kinfu, Yohannes Defo, Barthelemy Kuate Balaji, Arjun Lakshmana Lunevicius, Raimundas Obermeyer, Carla Makhlouf Malekzadeh, Reza Mansourian, Morteza Marcenes, Wagner Farid, Habibolah Masoudi Mehari, Alem Memish, Ziad A. Mehio-Sibai, Abla Memish, Ziad A. Mensah, George A. Mohammad, Karzan A. Nahas, Ziad Nasher, Jamal T. Nawaz, Haseeb Nejjari, Chakib Nisar, Muhammad Imran Omer, Saad B. Parsaeian, Mahboubeh Peprah, Emmanuel K. Pervaiz, Aslam Pourmalek, Farshad Qato, Dima M. Qorbani, Mostafa Radfar, Amir Rafay, Anwar Rahimi, Kazem Rahimi-Movaghar, Vafa Rahman, Sajjad Ur Rai, Rajesh K. Rana, Saleem M. Rao, Sowmya R. Refaat, Amany H. Resnikoff, Serge Roshandel, Gholamreza Saade, Georges Saeedi, Mohammad Y. Sahraian, Mohammad Ali Saleh, Shadi Sanchez-Riera, Lidia Satpathy, Maheswar Sepanlou, Sadaf G. Setegn, Tesfaye Shaheen, Amira Shahraz, Saeid Sheikhbahaei, Sara Shishani, Kawkab Sliwa, Karen Tavakkoli, Mohammad Terkawi, Abdullah S. Uthman, Olalekan A. Westerman, Ronny Younis, Mustafa Z. Zaki, Maysaa El Sayed Zannad, Faiez Roth, Gregory A. Wang, Haidong Naghavi, Mohsen Vos, Theo Al Rabeeah, Abdullah A. Lopez, Alan D. Murray, Christopher J. L. TI Health in times of uncertainty in the eastern Mediterranean region, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013 SO LANCET GLOBAL HEALTH LA English DT Article ID 188 COUNTRIES; INJURIES; DISABILITY; MORTALITY AB Background The eastern Mediterranean region is comprised of 22 countries: Afghanistan, Bahrain, Djibouti, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Pakistan, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Syria, Tunisia, the United Arab Emirates, and Yemen. Since our Global Burden of Disease Study 2010 (GBD 2010), the region has faced unrest as a result of revolutions, wars, and the so-called Arab uprisings. The objective of this study was to present the burden of diseases, injuries, and risk factors in the eastern Mediterranean region as of 2013. Methods GBD 2013 includes an annual assessment covering 188 countries from 1990 to 2013. The study covers 306 diseases and injuries, 1233 sequelae, and 79 risk factors. Our GBD 2013 analyses included the addition of new data through updated systematic reviews and through the contribution of unpublished data sources from collaborators, an updated version of modelling software, and several improvements in our methods. In this systematic analysis, we use data from GBD 2013 to analyse the burden of disease and injuries in the eastern Mediterranean region specifically. Findings The leading cause of death in the region in 2013 was ischaemic heart disease (90.3 deaths per 100 000 people), which increased by 17.2% since 1990. However, diarrhoeal diseases were the leading cause of death in Somalia (186.7 deaths per 100 000 people) in 2013, which decreased by 26 . 9% since 1990. The leading cause of disability-adjusted life-years (DALYs) was ischaemic heart disease for males and lower respiratory infection for females. High blood pressure was the leading risk factor for DALYs in 2013, with an increase of 83 . 3% since 1990. Risk factors for DALYs varied by country. In low-income countries, childhood wasting was the leading cause of DALYs in Afghanistan, Somalia, and Yemen, whereas unsafe sex was the leading cause in Djibouti. Non-communicable risk factors were the leading cause of DALYs in high-income and middle-income countries in the region. DALY risk factors varied by age, with child and maternal malnutrition affecting the younger age groups (aged 28 days to 4 years), whereas high bodyweight and systolic blood pressure affected older people (aged 60-80 years). The proportion of DALYs attributed to high body-mass index increased from 3.7% to 7.5% between 1990 and 2013. Burden of mental health problems and drug use increased. Most increases in DALYs, especially from non-communicable diseases, were due to population growth. The crises in Egypt, Yemen, Libya, and Syria have resulted in a reduction in life expectancy; life expectancy in Syria would have been 5 years higher than that recorded for females and 6 years higher for males had the crisis not occurred. Interpretation Our study shows that the eastern Mediterranean region is going through a crucial health phase. The Arab uprisings and the wars that followed, coupled with ageing and population growth, will have a major impact on the region's health and resources. The region has historically seen improvements in life expectancy and other health indicators, even under stress. However, the current situation will cause deteriorating health conditions for many countries and for many years and will have an impact on the region and the rest of the world. Based on our findings, we call for increased investment in health in the region in addition to reducing the conflicts. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. C1 [Mokdad, Ali H.; Forouzanfar, Mohammad Hossein; Daoud, Farah; El Bcheraoui, Charbel; Moradi-Lakeh, Maziar; Khalil, Ibrahim; Afshin, Ashkan; Tuffaha, Marwa; Charara, Raghid; Barber, Ryan M.; Wagner, Joseph; Cercy, Kelly; Kravitz, Hannah; Coates, Matthew M.; Robinson, Margaret; Estep, Kara; Steiner, Caitlyn; Jaber, Sara; Mokdad, Ali A.; O'Rourke, Kevin F.; Roth, Gregory A.; Wang, Haidong; Naghavi, Mohsen; Vos, Theo; Lopez, Alan D.] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA USA. [Moradi-Lakeh, Maziar] Iran Univ Med Sci, Dept Community Med Prevent Med, Tehran, Iran. 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[Alkhateeb, Mohammad] King Khalid Univ Hosp, Dept Pediat, Riyadh, Saudi Arabia. [Aldhahri, Saleh F.; Altirkawi, Khalid A.] King Saud Univ, Riyadh, Saudi Arabia. [Terkawi, Abdullah S.] King Fahad Med City, Dept Anesthesiol, Riyadh, Saudi Arabia. [Aldhahri, Saleh F.] King Fahad Med City, Riyadh, Saudi Arabia. [Alghnam, Suliman] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. [Alhabib, Samia] King Abdullah Bin Abdulaziz Univ Hosp, Riyadh, Saudi Arabia. [Al-Hamad, Nawal] Publ Author Food & Nutr, Kuwait, Kuwait. [Deribew, Amare] Univ Oxford, Nuffield Dept Med, Oxford, England. [Ali, Raghib; Rahimi, Kazem] Univ Oxford, Oxford, England. [Ali, Syed Danish] Univ London, London, England. [Ali, Syed Danish] Inst & Fac Actuaries, Oxford, England. [Alomari, Mahmoud A.] Jordan Univ Sci & Technol, Div Phys Therapy, Dept Rehabil Sci, Irbid, Jordan. [Al-Sheyab, Nihaya] Jordan Univ Sci & Technol, Maternal & Child Hlth Dept, Irbid, Jordan. [Khader, Yousef] Jordan Univ Sci & Technol, Irbid, Jordan. [Alsharif, Ubai] Charite, Berlin, Germany. [Alsowaidi, Shirina] Univ Al Ain, Dept Internal Med, Al Ain, U Arab Emirates. [Khan, Gulfaraz] Coll Med & Hlth Sci, Dept Microbiol & Immunol, Al Ain, U Arab Emirates. [Al-Thani, Mohamed; Khalifa, Shams Eldin A.] Supreme Council Hlth, Doha, Qatar. [Amare, Azmeraw T.] Univ Adelaide, Discipline Psychiat, Sch Med, Adelaide, SA, Australia. [Amare, Azmeraw T.] Bahir Dar Univ, Coll Med & Hlth Sci, Bahir Dar, Ethiopia. [Setegn, Tesfaye] Bahir Dar Univ, Bahir Dar, Ethiopia. [Amini, Heresh] Kurdistan Univ Med Sci, Environm Hlth Res Ctr, Sanandaj, Iran. [Amini, Heresh] Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland. [Amini, Heresh] Univ Basel, Basel, Switzerland. [Ammar, Walid; Harb, Hilda L.] Minist Publ Hlth, Beirut, Lebanon. [Anwari, Palwasha] Minist Publ Hlth, Kabul, Afghanistan. [Asayesh, Hamid] Qom Univ Med Sci, Sch Paramed, Dept Emergency Med, Qom, Iran. [Asghar, Rana] South Asian Publ Hlth Forum, Islamabad, Pakistan. [Assabri, Ali M.] Sanaa Univ, Fac Med & Hlth Sci, Sanaa, Yemen. [Assadi, Reza] Mashhad Univ Med Sci, Mashhad, Iran. [Bacha, Umar] Univ Management & Technol, Sch Hlth Sci, Lahore, Pakistan. [Badawi, Alaa] Publ Hlth Agcy Canada, Toronto, ON, Canada. [Bakfalouni, Talal] Minist Hlth, Damascus, Syria. [Bazargan-Hejazi, Shahrzad] Charles R Drew Univ Med & Sci, Los Angeles, CA USA. [Bedi, Neeraj] Coll Publ Hlth & Trop Med, Jazan, Saudi Arabia. [Bhakta, Amit R.] Natl Inst Mental Hlth, Montgomery, MD USA. [Durrani, Adnan M.] NHLBI, Ctr Translat Res & Implementat Sci, Montgomery, MD USA. [Bhutta, Zulfiqar A.] Aga Khan Univ, Ctr Excellence Women & Child Hlth, Karachi, Pakistan. [Das, Jai] Aga Khan Univ, Dept Paediat & Child Hlth, Karachi, Pakistan. [Nisar, Muhammad Imran] Aga Khan Univ, Karachi, Pakistan. [Bhutta, Zulfiqar A.] Hosp Sick Children, Ctr Global Child Hlth, Toronto, ON, Canada. [Bin Abdulhak, Aref A.] Univ Iowa, Hosp & Clin, Iowa City, IA USA. [Boufous, Soufiane] Univ New South Wales, Transport & Rd Safety TARS Res, Sydney, NSW, Australia. [Resnikoff, Serge] Univ New South Wales, Brien Holden Vision Inst, Sydney, NSW, Australia. [Bourne, Rupert R. A.] Anglia Ruskin Univ, Vision Eye Res Unit, Cambridge, England. [Danawi, Hadi; Refaat, Amany H.] Walden Univ, Minneapolis, MN USA. [Deribew, Amare] KEMRI Wellcome Trust Res Programme, Kilifi, Kenya. [Elshrek, Yousef] Univ Tripoli, Fac Agr, Dept Food Sci, Tripoli, Libya. [Eshrati, Babak] Minist Hlth & Med Educ, Tehran, Iran. [Eshrati, Babak] Arak Univ Med Sci, Arak, Iran. [Esteghamati, Alireza; Hafezi-Nejad, Nima; Sheikhbahaei, Sara] Univ Tehran Med Sci, Endocrinol & Metab Res Ctr, Tehran, Iran. [Farzadfar, Farshad; Kasaeian, Amir; Khosravi, Ardeshir; Parsaeian, Mahboubeh] Univ Tehran Med Sci, Endocrinol & Metab Res Ctr, Non Communicable Dis Res Ctr, Tehran, Iran. [Hassanvand, Mohammad Sadegh] Univ Tehran Med Sci, Ctr Air Pollut Res, Inst Environm Res, Tehran, Iran. [Heydarpour, Pouria; Sahraian, Mohammad Ali] Univ Tehran Med Sci, Neurosci Inst, Multiple Sclerosis Res Ctr, Tehran, Iran. [Kasaeian, Amir] Univ Tehran Med Sci, Hematol Oncol & Stem Cell Transplantat Res Ctr, Tehran, Iran. [Malekzadeh, Reza; Roshandel, Gholamreza; Sepanlou, Sadaf G.] Univ Tehran Med Sci, Digest Dis Res Inst, Tehran, Iran. [Parsaeian, Mahboubeh] Univ Tehran Med Sci, Dept Epidemiol Biostat, Sch Publ Hlth, Tehran, Iran. [Rahimi-Movaghar, Vafa] Univ Tehran Med Sci, Sina Trauma & Surg Res Ctr, Tehran, Iran. [Faghmous, Imad A. D.] London Sch Hyg & Trop Med, London, England. [Zannad, Faiez] Univ Lorraine, INSERM, Clin Invest Ctr, Vandoeuvre Les Nancy, France. [Zannad, Faiez] CHU Nancy, Vandoeuvre Les Nancy, France. [Fereshtehnejad, Seyed-Mohammad] Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden. [Filip, Irina] Kaiser Permanente Psychiat Residency Program, Fontana, CA USA. [Fischer, Florian] Univ Bielefeld, Bielefeld, Germany. [Gankpe, Fortune G.] Leras Afrique, Cotonou, Benin. [Gankpe, Fortune G.] CHU Hassan II, Fes, Morocco. [Ginawi, Ibrahim] Univ Hail, Coll Med, Hail, Saudi Arabia. [Gishu, Melkamu Dedefo] Haramaya Univ, Dira Dawa, Ethiopia. [Gishu, Melkamu Dedefo] Kersa Hlth & Demog Surveillance Syst, Harar, Ethiopia. [Gupta, Rahul] West Virginia Bur Publ Hlth, Charleston, WV USA. [Hamadeh, Randah R.] Arabian Gulf Univ, Manama, Bahrain. [Hamdouni, Hayet] Minist Hlth, Direct Soins Sante Base, Tunis, Tunisia. [Hamidi, Samer] Hamdan Bin Mohammed Smart Univ, Dubai, U Arab Emirates. [Hedayati, Mohammad T.] Mazndaran Univ Med Sci, Sch Med, Dept Med Mycol & Parasitol, Sari, Iran. [Hsairi, Mohamed] Salah Azaiz Inst, Tunis, Tunisia. [Husseini, Abdullatif] Qatar Univ, Doha, Qatar. [Jahanmehr, Nader] Shahid Beheshti Univ Med Sci, Sch Publ Hlth, Tehran, Iran. [Jha, Vivekanand] Univ Oxford, George Inst Global Hlth India, New Delhi, India. [Jonas, Jost B.] Heidelberg Univ, Dept Ophthalmol, Med Fac Mannheim, Mannheim, Germany. [Karam, Nadim E.] Univ Balamand, Beirut, Lebanon. [Kassa, Nega Assefa] Haramaya Univ, Harari, Ethiopia. [Kaul, Anil] Oklahoma State Univ, Ctr Hlth Sci, Tulsa, OK USA. [Khan, Ejaz A.] Hlth Serv Acad, Islamabad, Pakistan. [Khoja, Tawfi K.] Hlth Ministers Council Cooperat Council States, Riyadh, Saudi Arabia. [Khosravi, Ardeshir] Iranian Minist Hlth & Med Educ, Tehran, Iran. [Kinfu, Yohannes] Univ Canberra, Fac Hlth, Ctr Res & Action Publ Hlth, Canberra, ACT, Australia. [Defo, Barthelemy Kuate] Univ Montreal, Dept Demog, Montreal, PQ, Canada. [Defo, Barthelemy Kuate] Univ Montreal, Publ Hlth Res Inst, Montreal, PQ, Canada. [Defo, Barthelemy Kuate] Univ Montreal, Dept Social & Prevent Med, Sch Publ Hlth, Montreal, PQ, Canada. [Balaji, Arjun Lakshmana] Indegene, Bangalore, Karnataka, India. [Lopez, Alan D.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Melbourne, Vic, Australia. [Lunevicius, Raimundas] Aintree Univ Hosp NHS Fdn Trust, Natl Hlth Serv Fdn, Liverpool, Merseyside, England. [Lunevicius, Raimundas] Univ Liverpool, Sch Med, Liverpool, Merseyside, England. [Obermeyer, Carla Makhlouf] Amer Univ Beirut, Ctr Res Populat & Hlth, Fac Hlth Sci, Beirut, Lebanon. [Mehio-Sibai, Abla] Amer Univ Beirut, Dept Epidemiol & Populat Hlth, Fac Hlth Sci, Beirut, Lebanon. [Nahas, Ziad] Amer Univ Beirut, Med Ctr, Beirut, Lebanon. [Saleh, Shadi] Amer Univ Beirut, Dept Hlth Management & Policy, Beirut, Lebanon. [Marcenes, Wagner] Univ London, London, England. [Farid, Habibolah Masoudi] State Welf Org, Tehran, Iran. [Mehari, Alem] Howard Univ, Coll Med, Washington, DC USA. [Memish, Ziad A.] Alfaisal Univ, Coll Med, Riyadh, Saudi Arabia. [Mohammad, Karzan A.] Univ Salahaddin, Erbil, Iraq. [Nasher, Jamal T.] Minist Publ Hlth & Populat, Sanaa, Yemen. [Nawaz, Haseeb] Southern Illinois Univ, Springfield, IL USA. [Nejjari, Chakib] Fac Med, Fes, Morocco. [Omer, Saad B.] Emory Univ, Atlanta, GA USA. [Peprah, Emmanuel K.] NHLBI, Bldg 10, Bethesda, MD 20892 USA. [Pervaiz, Aslam] Postgrad Med Inst, Lahore, Pakistan. [Pourmalek, Farshad] Univ British Columbia, Vancouver, BC, Canada. [Qato, Dima M.] Univ Illinois, Coll Pharm, Chicago, IL USA. [Qorbani, Mostafa] Alborz Univ Med, Sch Med, Dept Commun Med, Karaj, Iran. [Radfar, Amir] AT Still Univ Hlth Sci, Kirksville, MO USA. [Rafay, Anwar; Rana, Saleem M.] Contech Int Hlth Consultants, Lahore, Pakistan. [Rahman, Sajjad Ur] Hamad Med Corp, Doha, Qatar. [Rai, Rajesh K.] Soc Hlth & Demog Surveillance, Suri, India. [Rana, Saleem M.] Contech Sch Publ Hlth, Lahore, Pakistan. [Rao, Sowmya R.] Boston Univ, Sch Med, Dept Surg, Boston, MA USA. [Refaat, Amany H.] Suez Canal Univ, Ismailia, Egypt. [Resnikoff, Serge] Int Hlth & Dev, Geneva, Switzerland. [Roshandel, Gholamreza] Golestan Univ Med Sci, Golestan Res Ctr Gastroenterol & Hepatol, Gorgan, Iran. [Saade, Georges] Lebanese Univ, Beirut, Lebanon. [Saade, Georges] Bellevue Med Ctr, Mansourieh El Metn, Lebanon. [Sanchez-Riera, Lidia] Hosp Llobregat, IDIBELL, Barcelona, Spain. [Satpathy, Maheswar] All India Inst Med Sci, New Delhi, India. [Shaheen, Amira] An Najah Univ, Dept Publ Hlth, Nablus, Israel. [Shahraz, Saeid] Tufts Med Ctr, Boston, MA USA. [Shishani, Kawkab] Washington State Univ, Spokane, WA USA. [Sliwa, Karen] Univ Cape Town, Fac Hlth Sci, Hatter Inst Cardiovascular Res Afr, Cape Town, South Africa. [Tavakkoli, Mohammad] Westchester Med Ctr, Valhalla, NY USA. [Terkawi, Abdullah S.] Univ Virginia, Dept Anesthesiol, Charlottesville, VA USA. [Uthman, Olalekan A.] Univ Warwick, Warwick Med Sch, Warwick, England. [Westerman, Ronny] Fed Inst Populat Res, Wiesbaden, Germany. [Westerman, Ronny] German Natl Cohort Consortium, Heidelberg, Germany. [Younis, Mustafa Z.] Jackson State Univ, Jackson, MS USA. [Zaki, Maysaa El Sayed] Mansoura Univ, Fac Med, Mansoura, Egypt. RP Mokdad, AH (reprint author), Inst Hlth Metr & Evaluat, Seattle, WA 98121 USA. EM mokdaa@uw.edu RI Gishu, Melkamu Dedefo/C-3747-2017; Alsharif, Ubai/C-6527-2017; Amini, Heresh/B-3076-2010; Altirkawi, Khalid/D-7302-2017; Hedayati, Mohammad T./E-2304-2017; OI Gishu, Melkamu Dedefo/0000-0002-3466-1232; Alsharif, Ubai/0000-0002-4024-3950; Amini, Heresh/0000-0002-4825-1322; Altirkawi, Khalid/0000-0002-7331-4196; Hedayati, Mohammad T./0000-0001-6415-4648; assadi, reza/0000-0002-5016-2994; Heydarpour, Pouria/0000-0001-5644-7555; Husseini, Abdullatif/0000-0001-8767-5956; Uthman, Olalekan/0000-0002-8567-3081 FU Bill & Melinda Gates Foundation FX Funding Bill & Melinda Gates Foundation. NR 20 TC 4 Z9 4 U1 21 U2 21 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2214-109X J9 LANCET GLOB HEALTH JI Lancet Glob. Health PD OCT PY 2016 VL 4 IS 10 BP E704 EP E713 DI 10.1016/S2214-109X(16)30168-1 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DW7RE UT WOS:000383848000021 PM 27568068 ER PT J AU Bauss, F Lechmann, M Krippendorff, BF Staack, R Herting, F Festag, M Imhof-Jung, S Hesse, F Pompiati, M Kollmorgen, G Seidl, RDM Bossenmaier, B Lau, W Schantz, C Stracke, JO Brinkmann, U Onda, M Pastan, I Bosslet, K Niederfellner, G AF Bauss, Frieder Lechmann, Martin Krippendorff, Ben-Fillippo Staack, Roland Herting, Frank Festag, Matthias Imhof-Jung, Sabine Hesse, Friederike Pompiati, Marc Kollmorgen, Gwendlyn Seidl, Rita da Silva Mateus Bossenmaier, Birgit Lau, Wilma Schantz, Christian Stracke, Jan O. Brinkmann, Ulrich Onda, Masanori Pastan, Ira Bosslet, Klaus Niederfellner, Gerhard TI Characterization of a re-engineered, mesothelin-targeted Pseudomonas exotoxin fusion protein for lung cancer therapy SO MOLECULAR ONCOLOGY LA English DT Article DE Immunotoxin; De-immunization; Pharmacokinetics; Lung cancer; Patient-derived xenografts; Targeted therapy ID VASCULAR LEAK SYNDROME; B-CELL EPITOPES; RECOMBINANT IMMUNOTOXIN; AERUGINOSA EXOTOXIN; PANCREATIC-CANCER; TUMOR XENOGRAFTS; KUPFFER CELLS; IN-VITRO; PHASE-I; MICE AB Mesothelin overexpression in lung adenocarcinomas correlates with the presence of activating KRAS mutations and poor prognosis. Hence SS1P, a mesothelin-targeted immunotoxin, could offer valuable treatment options for these patients, but its use in solid tumor therapy is hampered by high immunogenicity and non-specific toxicity. To overcome both obstacles we developed RG7787, a de-immunized cytotoxic fusion protein comprising a humanized SS1 Fab fragment and a truncated, B-cell epitope silenced, 24 kD fragment of Pseudomonas exotoxin A (PE24). Reactivity of RG7787 with sera from immunotoxin-treated patients was >1000 fold reduced. In vitro RG7787 inhibited cell viability of lung cancer cell lines with picomolar potency. The pharmacokinetic properties of RG7787 in rodents were comparable to SS1P, yet it was tolerated up to 10 fold better without causing severe vascular leak syndrome or hepatotoxicity. A pharmacokinetic/pharmacodynamic model developed based on NCI-H596 xenograft studies showed that for RG7787 and SS1P, their in vitro and in vivo potencies closely correlate. At optimal doses of 2-3 mg/kg RG7787 is more efficacious than SS1P. Even large, well established tumors (600 mm(3)) underwent remission during three treatment cycles with RG7787. Also in two patient-derived lung cancer xenograft models, Lu7336 and Lu7187, RG7787 showed antitumor efficacy. In monotherapy two treatment cycles were moderately efficacious in the Lu7336 model but showed good anti-tumor activity in the KRAS mutant Lu7187 model (26% and 80% tumor growth inhibition, respectively). Combination of RG7787 with standard chemotherapies further enhanced efficacy in both models achieving near complete eradication of Lu7187 tumors. (C) 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 [Bauss, Frieder; Herting, Frank; Kollmorgen, Gwendlyn; Seidl, Rita da Silva Mateus; Bossenmaier, Birgit; Bosslet, Klaus; Niederfellner, Gerhard] Roche Diagnost GmbH Penzberg, Innovat Ctr Munich, Roche Pharma Res & Early Dev pRED, Discovery Oncol, Nonnenwald 2, D-82377 Penzberg, Germany. [Lechmann, Martin; Staack, Roland] Roche Diagnost GmbH Penzberg, Innovat Ctr Munich, Roche Pharma Res & Early Dev pRED, Pharmaceut Sci, Nonnenwald 2, D-82377 Penzberg, Germany. [Imhof-Jung, Sabine; Hesse, Friederike; Pompiati, Marc; Lau, Wilma; Schantz, Christian; Stracke, Jan O.; Brinkmann, Ulrich] Roche Diagnost GmbH Penzberg, Innovat Ctr Munich, Roche Pharma Res & Early Dev pRED, Large Mol Res, Nonnenwald 2, D-82377 Penzberg, Germany. [Krippendorff, Ben-Fillippo; Festag, Matthias] F Hoffmann La Roche & Cie AG, Pharmaceut Sci, Roche pRED Innovat Ctr Basel, Grenzacherstr 124, CH-4070 Basel, Switzerland. [Onda, Masanori; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, Bldg 37, Bethesda, MD 20892 USA. [Stracke, Jan O.] F Hoffmann La Roche Ltd, Pharmaceut Dev & Supplies, Pharma Tech Dev Biol Europe, Basel, Switzerland. RP Niederfellner, G (reprint author), Roche Diagnost GmbH Penzberg, Nonnenwald 2, D-82377 Penzberg, Germany. EM gerhard.niederfellner@roche.com FU Center for Cancer Research of the National Cancer Institute; Roche Pharmaceuticals FX This research was supported by the Center for Cancer Research of the National Cancer Institute and by a Cooperative Research and Development Agreement with Roche Pharmaceuticals for the development of Pseudomonas exotoxin-derived entities in targeted cancer therapy. NR 47 TC 1 Z9 1 U1 7 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1574-7891 EI 1878-0261 J9 MOL ONCOL JI Mol. Oncol. PD OCT PY 2016 VL 10 IS 8 BP 1317 EP 1329 DI 10.1016/j.molonc.2016.07.003 PG 13 WC Oncology SC Oncology GA DX5AJ UT WOS:000384391900015 PM 27507537 ER PT J AU Surendran, P Drenos, F Young, R Warren, H Cook, JP Manning, AK Grarup, N Sim, X Barnes, DR Witkowska, K Staley, JR Tragante, V Tukiainen, T Yaghootkar, H Masca, N Freitag, DF Ferreira, T Giannakopoulou, O Tinker, A Harakalova, M Mihailov, E Liu, C Kraja, AT Nielsen, SF Rasheed, A Samue, M Zhao, W Bonnycastle, LL Jackson, AU Narisu, N Swift, AJ Southam, L Marten, J Huyghe, JR Stancakova, A Fava, C Ohlsson, T Matchan, A Stirrups, KE Bork-Jensen, J Gjesing, AP Kontto, J Perola, M Shaw-Hawkins, S Havulinna, AS Zhang, H Donnelly, LA Groves, CJ Rayner, NW Neville, MJ Robertson, NR Yiorkas, AM Herzig, KH Kajantie, E Zhang, W Willems, SM Lannfelt, L Malerba, G Soranzo, N Trabetti, E Verweij, N Evangelou, E Moayyeri, A Vergnaud, AC Nelson, CP Poveda, A Varga, TV Caslake, M de Craen, AJM Trompet, S Luan, J Scott, RA Harris, SE Liewald, DCM Marioni, R Menni, C Farmaki, AE Hallmans, G Renstrom, F Huffman, JE Hassinen, M Burgess, S Vasan, RS Felix, JF Uria-Nickelsen, M Malarstign, A Reilly, DF Hoek, M Vogt, TF Lin, HH Lieb, W Traylor, M Markus, HS Highland, HM Justice, AE Marouli, E Lindstrom, J Uusitupa, M Komulainen, P Lakka, TA Rauramaa, R Polasek, O Rudan, I Rolandsson, O Franks, PW Dedoussis, G Spector, TD Jousilahti, P Mannisto, S Deary, IJ Starr, JM Langenberg, C Wareham, NJ Brown, MJ Dominiczak, AF Connell, JM Jukema, JW Sattar, N Ford, I Packard, CJ Esko, T Magi, R Metspalu, A de Boer, RA van der Meer, P van der Harst, P Gambaro, G Ingelsson, E Lind, L de Bakker, PIW Numans, ME Brandslund, I Christensen, C Petersen, ERB Korpi-Hyovalti, E Oksa, H Chambers, JC Kooner, JS Blakemore, AIF Franks, S Jarvelin, MR Husemoen, LL Linneberg, A Skaaby, T Thuesen, B Karpe, F Tuomilehto, J Doney, ASF Morris, AD Palmer, CNA Holmen, OL Hveem, K Willer, CJ Tuomi, T Groop, L Karajamaki, A Palotie, A Ripatti, S Salomaa, V Alam, DS Majmnder, AAS Di Angelantonio, E Chowdhury, R McCarthy, MI Poulter, N Stanton, AV Sever, P Amouyel, P Arveiler, D Blankenberg, S Ferrieres, J Kee, F Kuulasmaa, K Muller-Nurasyid, M Veronesi, G Virtamo, J Deloukas, P Elliott, P Zeggini, E Kathiresan, S Melander, O Kuusisto, J Laakso, M Padmanabhan, S Porteous, DJ Hayward, C Scotland, G Collins, FS Mohlke, KL Hansen, T Pedersen, O Boehnke, M Stringham, HM Frossard, P Newton-Cheh, C Tobin, MD Nordestgaard, BG Caulfield, MJ Mahajan, A Morris, AP Tomaszewski, M Samani, NJ Saleheen, D Asselbergs, FW Lindgren, CM Danesh, J Wain, LV Butterworth, AS Howson, JMM Munroe, PB AF Surendran, Praveen Drenos, Fotios Young, Robin Warren, Helen Cook, James P. Manning, Alisa K. Grarup, Niels Sim, Xueling Barnes, Daniel R. Witkowska, Kate Staley, James R. Tragante, Vinicius Tukiainen, Taru Yaghootkar, Hanieh Masca, Nicholas Freitag, Daniel F. Ferreira, Teresa Giannakopoulou, Olga Tinker, Andrew Harakalova, Magdalena Mihailov, Evelin Liu, Chunyu Kraja, Aldi T. Nielsen, Sune Fallgaard Rasheed, Asif Samue, Maria Zhao, Wei Bonnycastle, Lori L. Jackson, Anne U. Narisu, Narisu Swift, Amy J. Southam, Lorraine Marten, Jonathan Huyghe, Jeroen R. Stancakova, Alena Fava, Cristiano Ohlsson, Therese Matchan, Angela Stirrups, Kathleen E. Bork-Jensen, Jette Gjesing, Anette P. Kontto, Jukka Perola, Markus Shaw-Hawkins, Susan Havulinna, Aki S. Zhang, He Donnelly, Louise A. Groves, Christopher J. Rayner, N. William Neville, Matt J. Robertson, Neil R. Yiorkas, Andrianos M. Herzig, Karl-Heinz Kajantie, Eero Zhang, Weihua Willems, Sara M. Lannfelt, Lars Malerba, Giovanni Soranzo, Nicole Trabetti, Elisabetta Verweij, Niek Evangelou, Evangelos Moayyeri, Alireza Vergnaud, Anne-Claire Nelson, Christopher P. Poveda, Alaitz Varga, Tibor V. Caslake, Muriel de Craen, Anton J. M. Trompet, Stella Luan, Jian'an Scott, Robert A. Harris, Sarah E. Liewald, David C. M. Marioni, Riccardo Menni, Cristina Farmaki, Aliki-Eleni Hallmans, Goran Renstrom, Frida Huffman, Jennifer E. Hassinen, Maija Burgess, Stephen Vasan, Ramachandran S. Felix, Janine F. Uria-Nickelsen, Maria Malarstign, Anders Reilly, Dermot F. Hoek, Maarten Vogt, Thomas F. Lin, Honghuang Lieb, Wolfgang Traylor, Matthew Markus, Hugh S. Highland, Heather M. Justice, Anne E. Marouli, Eirini Lindstrom, Jaana Uusitupa, Matti Komulainen, Pirjo Lakka, Timo A. Rauramaa, Rainer Polasek, Ozren Rudan, Igor Rolandsson, Olov Franks, Paul W. Dedoussis, George Spector, Timothy D. Jousilahti, Pekka Mannisto, Satu Deary, Ian J. Starr, John M. Langenberg, Claudia Wareham, Nick J. Brown, Morris J. Dominiczak, Anna F. Connell, John M. Jukema, J. Wouter Sattar, Naveed Ford, Ian Packard, Chris J. Esko, Tonu Magi, Reedik Metspalu, Andres de Boer, Rudolf A. van der Meer, Peter van der Harst, Pim Gambaro, Giovanni Ingelsson, Erik Lind, Lars de Bakker, Paul I. W. Numans, Mattijs E. Brandslund, Ivan Christensen, Cramer Petersen, Eva R. B. Korpi-Hyovalti, Eeva Oksa, Heikki Chambers, John C. Kooner, Jaspal S. Blakemore, Alexandra I. F. Franks, Steve Jarvelin, Marjo-Riitta Husemoen, Lise L. Linneberg, Allan Skaaby, Tea Thuesen, Betina Karpe, Fredrik Tuomilehto, Jaakko Doney, Alex S. F. Morris, Andrew D. Palmer, Colin N. A. Holmen, Oddgeir Lingaas Hveem, Kristian Willer, Cristen J. Tuomi, Tiinamaija Groop, Leif Karajamaki, AnneMari Palotie, Aarno Ripatti, Samuli Salomaa, Veikko Alam, Dewan S. Majmnder, Abdulla Al Shafi Di Angelantonio, Emanuele Chowdhury, Rajiv McCarthy, Mark I. Poulter, Neil Stanton, Alice V. Sever, Peter Amouyel, Philippe Arveiler, Dominique Blankenberg, Stefan Ferrieres, Jean Kee, Frank Kuulasmaa, Kari Muller-Nurasyid, Martina Veronesi, Giovanni Virtamo, Jarmo Deloukas, Panos Elliott, Paul Zeggini, Eleftheria Kathiresan, Sekar Melander, Olle Kuusisto, Johanna Laakso, Markku Padmanabhan, Sandosh Porteous, David J. Hayward, Caroline Scotland, Generation Collins, Francis S. Mohlke, Karen L. Hansen, Torben Pedersen, Oluf Boehnke, Michael Stringham, Heather M. Frossard, Philippe Newton-Cheh, Christopher Tobin, Martin D. Nordestgaard, Borge Gronne Caulfield, Mark J. Mahajan, Anubha Morris, Andrew P. Tomaszewski, Maciej Samani, Nilesh J. Saleheen, Danish Asselbergs, Folkert W. Lindgren, Cecilia M. Danesh, John Wain, Louise V. Butterworth, Adam S. Howson, Joanna M. M. Munroe, Patricia B. CA CHARGE Heart Failure Consortiumm EchoGen Consortiumm Metastroke Consortiumm Giant Consortiumm EPIC-InterAct Consortium Lifelines Cohort Study Wellcome Trust Case Control Consor Understanding Soc Sci Grp EPIC-CVD Consortium CHARGE Exome Chip Blood Pressure C T2D-GENES Consortium GoT2DGenes Consortium ExomeBP Consortium CHD Exome Consortium TI Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; GENE-CENTRIC ARRAY; CARDIOVASCULAR-DISEASE; AGING RESEARCH; PLASMA-LEVELS; RISK-FACTORS; LOCI; CHARGE; HEART; IDENTIFICATION AB High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low frequency and common genetic variants in up to 192,763 individuals and used similar to 155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention. 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[Danesh, John; Munroe, Patricia B.] Wellcome Trust Sanger Inst, Hinxton, England. RP Howson, JMM (reprint author), Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England.; Howson, JMM (reprint author), Queen Mary Univ London, William Harvey Res Inst, Clin Pharmacol, London, England.; Howson, JMM (reprint author), Queen Mary Univ London, Natl Inst Hlth Res, Barts Cardiovasc Biomed Res Unit, London, England.; Howson, JMM; Munroe, PB (reprint author), Wellcome Trust Sanger Inst, Hinxton, England. EM jmmh2@medschl.cam.ac.uk; p.b.munroe@qmul.ac.uk RI Palmer, Colin/C-7053-2008; Deloukas, Panos/B-2922-2013; Padmanabhan, Sandosh/S-3963-2016; Verweij, Niek/A-4499-2017; Grarup, Niels/K-2807-2015; Lieb, Wolfgang/C-1990-2012; Polasek, Ozren/B-6002-2011; OI Palmer, Colin/0000-0002-6415-6560; Deloukas, Panos/0000-0001-9251-070X; Grarup, Niels/0000-0001-5526-1070; Polasek, Ozren/0000-0002-5765-1862; Traylor, Matthew/0000-0001-6624-8621; Kuulasmaa, Kari/0000-0003-2165-1411; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Tuomi, Tiinamaija/0000-0002-8306-6202; Varga, Tibor/0000-0002-2383-699X; Evangelou, Evangelos/0000-0002-5488-2999; Kontto, Jukka/0000-0003-3899-9852; Burgess, Stephen/0000-0001-5365-8760; Linneberg, Allan/0000-0002-0994-0184; Wain, Louise/0000-0003-4951-1867; Skaaby, Tea/0000-0003-0031-5726 FU British Heart Foundation [RG/14/5/30893, RG/15/15/31742]; Chief Scientist Office [CZD/16/6/4]; Medical Research Council [G0600237, G0601966, G0700931, MC_PC_U127561128, MC_UU_12013/5, MC_UU_12015/1, MR/K006584/1, MR/K026992/1, MR/L01341X/1]; NHLBI NIH HHS [R01 HL127564]; NIDDK NIH HHS [U01 DK062370, P30 DK020595] NR 43 TC 8 Z9 8 U1 25 U2 25 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD OCT PY 2016 VL 48 IS 10 BP 1151 EP 1161 DI 10.1038/ng.3654 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA DX5AG UT WOS:000384391600010 PM 27618447 ER PT J AU Liu, CY Kraja, AT Smith, JA Brody, JA Franceschini, N Bis, JC Rice, K Morrison, AC Lu, YC Weiss, S Guo, XQ Palmas, W Martin, LW Chen, YDI Surendran, P Drenos, F Cook, JP Auer, PL Chu, AY Giri, A Zhao, W Jakobsdottir, J Lin, LA Stafford, JM Amin, N Mei, H Yao, J Voorman, A Larson, MG Grove, ML Smith, AV Hwang, SJ Chen, H Huan, T Kosova, G Stitziel, NO Kathiresan, S Samani, N Schunkert, H Deloukas, P Li, M Fuchsberger, C Pattaro, C Gorski, M Kooperberg, C Papanicolaou, GJ Rossouw, JE Paul, JD Kardia, SLR Bouchard, C Raffe, LF Uitterlinden, AG Franco, OH Vasan, RS O'Donnell, CJ Taylor, KD Liu, K Bottinger, EP Gottesman, O Daw, EW Giulianini, F Ganesh, S Salfati, E Harris, TB Launer, LJ Dorr, M Felix, SB Rettig, R Volzke, H Kim, E Lee, WJ Lee, IT Sheu, WHH Tsosie, KS Edwards, DRV Liu, YM Correa, A Weir, DR Volker, U Ridker, PM Boerwinkle, E Gudnason, V Reiner, AP van Duijn, CM Boreckill, IB Edwards, TL Chakravarti, A Rotter, JI Psaty, BM Loos, RJF Fornage, M Ehret, GB Newton-Cheh, C Levy, D Chasman, DI AF Liu, Chunyu Kraja, Aldi T. Smith, Jennifer A. Brody, Jennifer A. Franceschini, Nora Bis, Joshua C. Rice, Kenneth Morrison, Alanna C. Lu, Yingchang Weiss, Stefan Guo, Xiuqing Palmas, Walter Martin, Lisa W. Chen, Yii-Der Ida Surendran, Praveen Drenos, Fotios Cook, James P. Auer, Paul L. Chu, Audrey Y. Giri, Ayush Zhao, Wei Jakobsdottir, Johanna Lin, Li-An Stafford, Jeanette M. Amin, Najaf Mei, Hao Yao, Jie Voorman, Arend Larson, Martin G. Grove, Megan L. Smith, Albert V. Hwang, Shih-Jen Chen, Han Huan, Tiamdao Kosova, Gulum Stitziel, Nathan O. Kathiresan, Sekar Samani, Nilesh Schunkert, Heribert Deloukas, Panos Li, Man Fuchsberger, Christian Pattaro, Cristian Gorski, Mathias Kooperberg, Charles Papanicolaou, George J. Rossouw, Jacques E. Paul, Jessica D. Kardia, Sharon L. R. Bouchard, Claude Raffe, Leslie F. Uitterlinden, Andre G. Franco, Oscar H. Vasan, Ramachandran S. O'Donnell, Christopher J. Taylor, Kent D. Liu, Kiang Bottinger, Erwin P. Gottesman, Omri Daw, E. Warwick Giulianini, Franco Ganesh, Santhi Salfati, Elias Harris, Tamara B. Launer, Lenore J. Dorr, Marcus Felix, Stephan B. Rettig, Rainer Volzke, Henry Kim, Eric Lee, Wen-Jane Lee, I-Te Sheu, Wayne H-H Tsosie, Krystal S. Edwards, Digna R. Velez Liu, Yongmei Correa, Adolfo Weir, David R. Volker, Uwe Ridker, Paul M. Boerwinkle, Eric Gudnason, Vilmundur Reiner, Alexander P. van Duijn, Cornelia M. Boreckill, Ingrid B. Edwards, Todd L. Chakravarti, Aravinda Rotter, Jerome I. Psaty, Bruce M. Loos, Ruth J. F. Fornage, Myriam Ehret, Georg B. Newton-Cheh, Christopher Levy, Daniel Chasman, Daniel I. CA CHD Exome Consortium ExomeBP Consortium GOT2Dgenes Consortium T2D-Genes Consortium Myocardial Infarction Genetics CAR CKDGen Consortium TI Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; LIPOPROTEIN-LIPASE GENE; NATRIURETIC PEPTIDE RECEPTOR; SUSCEPTIBILITY LOCI; MONOGENIC FORMS; CENTRIC ARRAY; HYPERTENSION; DISEASE; EXPRESSION; RISK AB Meta-analyses of association results for blood pressure using exome-centric single-variant and gene-based tests identified 31 new loci in a discovery stage among 146,562 individuals, with follow-up and meta-analysis in 180,726 additional individuals (total n = 327,288). These blood pressure-associated loci are enriched for known variants for cardiometabolic traits. Associations were also observed for the aggregation of rare and low-frequency missense variants in three genes, NPR1, DBH, and PTPMT1. In addition, blood pressure associations at 39 previously reported loci were confirmed. The identified variants implicate biological pathways related to cardiometabolic traits, vascular function, and development. Several new variants are inferred to have roles in transcription or as hubs in protein-protein interaction networks. Genetic risk scores constructed from the identified variants were strongly associated with coronary disease and myocardial infarction. This large collection of blood pressure-associated loci suggests new therapeutic strategies for hypertension, emphasizing a link with cardiometabolic risk. C1 [Liu, Chunyu; Chu, Audrey Y.; Larson, Martin G.; Hwang, Shih-Jen; Huan, Tiamdao; Vasan, Ramachandran S.; O'Donnell, Christopher J.; Levy, Daniel] NHLBI, Framingham Heart Study, Framingham, MA USA. [Liu, Chunyu; Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Liu, Chunyu; Chu, Audrey Y.; Hwang, Shih-Jen; Huan, Tiamdao; Levy, Daniel] NHLBI, Populat Sci Branch, Bldg 10, Bethesda, MD 20892 USA. [Kraja, Aldi T.; Daw, E. Warwick; Boreckill, Ingrid B.] Washington Univ, Sch Med, Div Stat Genom, St Louis, MO USA. [Kraja, Aldi T.; Daw, E. Warwick; Boreckill, Ingrid B.] Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO USA. [Smith, Jennifer A.; Zhao, Wei; Kardia, Sharon L. R.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Brody, Jennifer A.; Bis, Joshua C.; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Franceschini, Nora] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Rice, Kenneth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Morrison, Alanna C.; Grove, Megan L.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Sch Publ Hlth, Houston, TX 77030 USA. [Lu, Yingchang; Bottinger, Erwin P.; Gottesman, Omri; Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA. [Weiss, Stefan; Dorr, Marcus; Felix, Stephan B.; Rettig, Rainer; Volzke, Henry; Volker, Uwe] DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany. [Weiss, Stefan; Volker, Uwe] Univ Med, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Weiss, Stefan; Correa, Adolfo; Volker, Uwe] Ernst Moritz Arndt Univ Greifswald, Greifswald, Germany. [Guo, Xiuqing; Chen, Yii-Der Ida; Yao, Jie; Taylor, Kent D.; Kim, Eric; Rotter, Jerome I.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA. [Guo, Xiuqing; Chen, Yii-Der Ida; Yao, Jie; Taylor, Kent D.; Kim, Eric; Rotter, Jerome I.] Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA. [Palmas, Walter] Columbia Univ, Med Ctr, Div Gen Med, New York, NY USA. [Martin, Lisa W.] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA. [Surendran, Praveen] Univ Cambridge, Dept Publ Hlth & Primary Care, Cardiovasc Epidemiol Unit, Cambridge, England. [Drenos, Fotios] UCL, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London, England. [Drenos, Fotios] Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Oakfield House, Bristol, Avon, England. [Cook, James P.] Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England. [Cook, James P.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England. [Auer, Paul L.] Univ Wisconsin, Joseph J Zilber Sch Publ Hlth, Milwaukee, WI 53201 USA. [Chu, Audrey Y.; Giulianini, Franco; Ridker, Paul M.; Levy, Daniel] Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA. [Giri, Ayush; Tsosie, Krystal S.; Edwards, Digna R. Velez; Edwards, Todd L.] Vanderbilt Univ, Vanderbilt Genet Inst, Inst Med & Publ Hlth, Vanderbilt Epidemiol Ctr,Med Ctr, Nashville, TN USA. [Jakobsdottir, Johanna; Smith, Albert V.; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Lin, Li-An; Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA. [Stafford, Jeanette M.] Wake Forest Sch Med, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC USA. [Amin, Najaf; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands. [Mei, Hao] Univ Mississippi, Med Ctr, Dept Data Sci, Sch Populat Hlth, Jackson, MS 39216 USA. [Voorman, Arend] Bill & Melinda Gates Fdn, Seattle, WA USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Smith, Albert V.] Univ Iceland, Fac Med, Reykjavik, Iceland. [Chen, Han] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Kosova, Gulum] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kosova, Gulum; Kathiresan, Sekar; Newton-Cheh, Christopher] Broad Inst MIT & Harvard, Program Med & Populat Genet, Boston, MA USA. [Stitziel, Nathan O.] Washington Univ, Dept Med, Sch Med, Div Cardiol, St Louis, MO USA. [Stitziel, Nathan O.] Washington Univ, Dept Genet, Sch Med, St Louis, MO USA. [Samani, Nilesh] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England. [Samani, Nilesh] Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England. [Schunkert, Heribert] Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany. [Schunkert, Heribert] DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Munich, Germany. [Deloukas, Panos] King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah, Saudi Arabia. [Deloukas, Panos] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England. [Li, Man] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Fuchsberger, Christian; Pattaro, Cristian] European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy. [Fuchsberger, Christian; Pattaro, Cristian] Univ Lubeck, Lubeck, Germany. [Gorski, Mathias] Univ Regensburg, Inst Epidemiol & Prevent Med, Dept Genet Epidemiol, Regensburg, Germany. [Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA. [Papanicolaou, George J.; Rossouw, Jacques E.] NHLBI, Div Cardiovasc Sci, Bldg 10, Bethesda, MD 20892 USA. [Paul, Jessica D.] Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI USA. [Bouchard, Claude] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Baton Rouge, LA USA. [Raffe, Leslie F.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Uitterlinden, Andre G.; Franco, Oscar H.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02215 USA. [O'Donnell, Christopher J.] Boston Vet Adm Healthcare, Cardiol Sect, Dept Med, Boston, MA USA. [O'Donnell, Christopher J.] Brigham & Womens Hosp, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. [O'Donnell, Christopher J.] Harvard Med Sch, Dept Med, Boston, MA USA. [Liu, Kiang] Northwestern Univ, Sch Med, Chicago, IL 60611 USA. [Ganesh, Santhi] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. [Ganesh, Santhi] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Salfati, Elias] Johns Hopkins Univ, Sch Med, Ctr Complex Dis Genom, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Harris, Tamara B.; Chakravarti, Aravinda; Ehret, Georg B.] NIA, Lab Epidemiol Demog & Biometry, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Launer, Lenore J.] NIA, Neuroepidemiol Sect, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Dorr, Marcus] Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany. [Rettig, Rainer] Ernst Moritz Arndt Univ Greifswald, Inst Physiol, Greifswald, Germany. [Volzke, Henry] DZD German Ctr Diabet Res, Site Greifswald, Greifswald, Germany. [Volzke, Henry] Univ Med Greifswald, Inst Community Med, Greifswald, Germany. [Lee, Wen-Jane] Taichung Vet Gen Hosp, Dept Med Res, Taichung, Taiwan. [Lee, I-Te; Sheu, Wayne H-H] Taichung Vet Gen Hosp, Dept Internal Med, Div Endocrinol & Metab, Taichung, Taiwan. [Sheu, Wayne H-H] Natl Yang Ming Univ, Sch Med, Taipei, Taiwan. [Lee, I-Te] Chung Shan Med Univ, Sch Med, Taichung, Taiwan. [Sheu, Wayne H-H] Natl Chung Hsing Univ, Inst Med Technol, Taichung, Taiwan. [Sheu, Wayne H-H] Natl Def Med Ctr, Sch Med, Taipei, Taiwan. [Edwards, Digna R. Velez] Vanderbilt Univ, Med Ctr, Dept Obstet & Gynecol, 221 Kirkland Hall, Nashville, TN 37235 USA. [Liu, Yongmei] Wake Forest Baptist Med Ctr, Epidemiol & Prevent Ctr Genom & Personalized Med, Winston Salem, NC USA. [Correa, Adolfo] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. [Ridker, Paul M.; Chasman, Daniel I.] Harvard Med Sch, Boston, MA USA. [Reiner, Alexander P.; Psaty, Bruce M.; Chasman, Daniel I.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Edwards, Todd L.] Vanderbilt Univ, Med Ctr, Dept Med, 221 Kirkland Hall, Nashville, TN 37235 USA. [Rotter, Jerome I.] Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Rotter, Jerome I.] Harbor UCLA Med Ctr, Dept Med, Torrance, CA 90509 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA. [Ehret, Georg B.] Univ Hosp Geneva, Cardiol, Geneva, Switzerland. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Liu, C; Levy, D (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA.; Liu, C (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.; Liu, C; Levy, D (reprint author), NHLBI, Populat Sci Branch, Bldg 10, Bethesda, MD 20892 USA.; Chasman, DI (reprint author), Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.; Chasman, DI (reprint author), Harvard Med Sch, Boston, MA USA. EM chunyu.liu@nih.gov; levyd@nhlbi.nih.gov; dchasman@research.bwh.harvard.edu RI Deloukas, Panos/B-2922-2013; Lin, LiAn/C-5819-2017; Bouchard, Claude/A-7637-2009; OI Deloukas, Panos/0000-0001-9251-070X; Lin, LiAn/0000-0003-2731-1346; Chen, Han/0000-0002-9510-4923; Smith, Jennifer/0000-0002-3575-5468 FU British Heart Foundation [RG/14/5/30893]; Medical Research Council [MC_UU_12013/5]; NHGRI NIH HHS [U01 HG004603, U01 HG004729]; NHLBI NIH HHS [R01 HL120393, HHSN268200800007C, HHSN268200900041C, HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, HHSN268201200036C, HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN268201300028C, HHSN268201300029C, HHSN268201300046C, N01 HC025195, N01 HC085079, N01 HC095159, N01HC55222, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, R01 HL068986, R01 HL080295, R01 HL084099, R01 HL087652, R01 HL093029, R01 HL103612, R01 HL105756, R01 HL117078, R21 HL121429, RC2 HL102419, T32 HL007208, U01 HL130114]; NIA NIH HHS [HHSN271201200022C, N01AG12100, R01 AG023629]; NIGMS NIH HHS [RC2 GM092618]; NIH HHS [S10 OD020069] NR 74 TC 6 Z9 6 U1 7 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD OCT PY 2016 VL 48 IS 10 BP 1162 EP 1170 DI 10.1038/ng.3660 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA DX5AG UT WOS:000384391600011 PM 27618448 ER PT J AU Ehret, GB Ferreira, T Chasman, DI Jackson, AU Schmidt, EM Johnson, T Thorleifsson, G Luan, J Donnelly, LA Kanoni, S Petersen, AK Pihurl, V Strawbridge, RJ Shungin, D Hughes, MF Meirelles, O Kaakinen, M Bouatia-Naji, N Kristiansson, K Shah, S Kleber, ME Guo, XQ Lyytikainen, LP Fava, C Eriksson, N Nolte, IM Magnusson, PK Salfati, EL Rallidis, LS Theusch, E Smith, AJP Folkersen, L Witkowska, K Pers, TH Joehanes, R Kim, SK Lataniotis, L Jansen, R Johnson, AD Warren, H Kim, YJ Zhao, W Wu, Y Tayo, BO Bochud, M Absher, D Adair, LS Amin, N Arkingl, DE Axelsson, T Baldassarre, D Balkau, B Bandinelli, S Barnes, MR Barroso, I Bevan, S Bis, JC Bjornsdottir, G Boehnke, M Boerwinkle, E Bonnycastle, LL Boomsma, DI Bornstein, SR Brown, MJ Burnier, M Cabrera, CP Chambers, JC Chang, IS Cheng, CY Chines, PS Chung, RH Collins, FS Connell, JM Doring, A Dallongeville, J Danesh, J de Faire, U Delgado, G Dominiczak, AF Doney, ASF Drenos, F Edkins, S Eicher, JD Elosua, R Enroth, S Erdmann, J Eriksson, P Esko, T Evangelou, E Evans, A Fai, T Farra, M Felixl, JF Ferrieres, J Ferrucci, L Fornage, M Forrester, T Franceschinil, N Franco, OH Franco-Cereceda, A Fraser, RM Ganesh, SK Gao, H Gertow, K Gianfagna, F Gigante, B Giulianini, F Goe, A Goodall, AH Goodarzi, M Gorski, M Grassler, J Groves, CJ Gudnason, V Gyllensten, U Hallmans, G Hartikainen, AL Hassinen, M Havulinna, AS Hayward, C Hercberg, S Herzig, KH Hicks, AA Hingorani, AD Hirschhorn, JN Hofmanl, A Holmen, J Holmen, OL Hottenga, JJ Howard, P Hsiung, CA Hunt, SC Ikram, MA Illig, T Iribarren, C Jensen, RA Kahonen, M Kang, HM Kathiresan, S Keating, BJ Khaw, KT Kim, YK Kim, E Kivimaki, M Klopp, N Kolovou, G Komulainen, P Kooner, JS Kosova, G Krauss, RM Kuh, D Kutalik, Z Kuusisto, J Kvaloy, K Lakka, TA Lee, NR Lee, IT Lee, WJ Levy, D Li, X Liang, KW Lin, H Lin, L Lindstrom, J Lobbens, S Mannisto, S Muller, G Muller-Nurasyid, M Mach, F Markus, HS Marouli, E McCarthy, MI McKenzie, CA Meneton, P Menni, C Metspalu, A Mijatovic, V Moilanen, L Montasser, ME Morris, AD Morrison, AC Mulas, A Nagaraja, R Narisu, N Nikus, K O'Donnell, CJ O'Reilly, PF Ong, KK Paccaud, F Palmer, CD Parsa, A Pedersen, NL Penninx, BW Perola, M Peters, A Poulter, N Pramstaller, PP Psaty, BM Quertermous, T Rao, DC Rasheed, A Rayner, NW Renstrom, F Rettig, R Rice, KM Roberts, R Rose, LM Rossouw, J Samani, NJ Sanna, S Saramies, J Schunkert, H Sebert, S Sheu, WHH Shin, YA Sim, X Smit, JH Smith, AV Sosa, MX Spector, TD Stancakova, A Stanton, AV Stirrups, KE Stringham, HM Sundstrom, J Swift, AJ Syvanen, AC Tai, ES Tanaka, T Tarasov, KV Teumer, A Thorsteinsdottir, U Tobin, MD Tremoli, E Uitterlinden, AG Uusitupa, M Vaez, A Vaidya, D van Duijn, CM van Iperen, EPA Vasan, RS Verwoert, GC Virtamo, J Vitart, V Voight, BF Vollenweider, P Wagner, A Wain, LV Wareham, NJ Watldns, H Weder, AB Westra, HJ Wilks, R Wilsgaard, T Wilson, JF Wong, TY Yang, TP Yao, J Yengo, L Zhang, W Zhao, JH Zhu, X Bovet, P Cooper, RS Mohlke, KL Saleheen, D Lee, JY Elliott, P Gierman, HJ Willer, CJ Franke, L Hovingh, GK Taylor, KD Dedoussis, G Sever, P Wong, A Lind, L Assimes, TL Njolstad, I Schwarz, PEH Langenberg, C Snieder, H Caulfield, MJ Melander, E Laakso, M Saltevo, J Rauramaa, R Tuomilehto, J Ingelsson, E Lehtimaki, T Hveem, K Palmas, W Marz, W Kumar, M Salomaa, V Chen, YDI Rotter, JI Froguel, P Jarvelin, MR Lakatta, EG Kuulasmaa, K Franks, PW Hamsten, A Wichmann, HE Palmer, CNA Stefansson, K Ridker, PM Loos, RJF Chalcravarti, A Deloukas, P Morris, AP Newton-Cheh, C Munroe, PB AF Ehret, Georg B. Ferreira, Teresa Chasman, Daniel I. Jackson, Anne U. Schmidt, Ellen M. Johnson, Toby Thorleifsson, Gudmar Luan, Jian'an Donnelly, Louise A. Kanoni, Stavroula Petersen, Ann -Kristin Pihurl, Vasyl Strawbridge, Rona J. Shungin, Dmitry Hughes, Maria F. Meirelles, Osorio Kaakinen, Marika Bouatia-Naji, Nabila Kristiansson, Kati Shah, Sonia Kleber, Marcus E. Guo, Xiuqing Lyytikainen, Leo-Pekka Fava, Cristiano Eriksson, Nidas Nolte, Ilja M. Magnusson, Patrik K. Salfati, Elias L. Rallidis, Loukianos S. Theusch, Elizabeth Smith, Andrew J. P. Folkersen, Lasse Witkowska, Kate Pers, Tune H. Joehanes, Roby Kim, Stuart K. Lataniotis, Lazaros Jansen, Rick Johnson, Andrew D. Warren, Helen Kim, Young Jin Zhao, Wei Wu, Ying Tayo, Bamidele O. Bochud, Murielle Absher, Devin Adair, Linda S. Amin, Najaf Arkingl, Dan E. Axelsson, Tomas Baldassarre, Damian Balkau, Beverley Bandinelli, Stefania Barnes, Michael R. Barroso, Ines Bevan, Stephen Bis, Joshua C. Bjornsdottir, Gyda Boehnke, Michael Boerwinkle, Eric Bonnycastle, Lori L. Boomsma, Dorret I. Bornstein, Stefan R. Brown, Morris J. Burnier, Michel Cabrera, Claudia P. Chambers, John C. Chang, I-Shou Cheng, Ching-Yu Chines, Peter S. Chung, Ren-Hua Collins, Francis S. Connell, John M. Doring, Angela Dallongeville, Jean Danesh, John de Faire, Ulf Delgado, Graciela Dominiczak, Anna F. Doney, Alex S. F. Drenos, Fotios Edkins, Sarah Eicher, John D. Elosua, Roberto Enroth, Stefan Erdmann, Jeanette Eriksson, Per Esko, Tonu Evangelou, Evangelos Evans, Alun Fai, Tove Farra, Martin Felixl, Janine F. Ferrieres, Jean Ferrucci, Luigi Fornage, Myriam Forrester, Terrence Franceschinil, Nora Franco, Oscar H. Franco-Cereceda, Anders Fraser, Ross M. Ganesh, Santhi K. Gao, He Gertow, Karl Gianfagna, Francesco Gigante, Bruna Giulianini, Franco Goe, Anuj Goodall, Alison H. Goodarzi, Mark Gorski, Mathias Grassler, Jurgen Groves, Christopher J. Gudnason, Vilmundur Gyllensten, Ulf Hallmans, Goran Hartikainen, Anna-Liisa Hassinen, Maija Havulinna, Aki S. Hayward, Caroline Hercberg, Serge Herzig, Karl-Heinz Hicks, Andrew A. Hingorani, Aroon D. Hirschhorn, Joel N. Hofmanl, Albert Holmen, Jostein Holmen, Oddgeir Lingaas Hottenga, Jouke-Jan Howard, Phil Hsiung, Chao A. Hunt, Steven C. Ikram, M. Arfan Illig, Thomas Iribarren, Carlos Jensen, Richard A. Kahonen, Mika Kang, Hyun Min Kathiresan, Sekar Keating, Brendan J. Khaw, Kay-Tee Kim, Yun Kyoung Kim, Eric Kivimaki, Mika Klopp, Norman Kolovou, Genovefa Komulainen, Pirjo Kooner, Jaspal S. Kosova, Gulum Krauss, Ronald M. Kuh, Diana Kutalik, Zoltan Kuusisto, Johanna Kvaloy, Kirsti Lakka, Timo A. Lee, Nanette R. Lee, I-Te Lee, Wen-Jane Levy, Daniel Li, Xiaohui Liang, Kae-Woei Lin, Honghuang Lin, Li Lindstrom, Jaana Lobbens, Stephane Mannisto, Satu Muller, Gabriele Muller-Nurasyid, Martina Mach, Francois Markus, Hugh S. Marouli, Eirini McCarthy, Mark I. McKenzie, Colin A. Meneton, Pierre Menni, Cristina Metspalu, Andres Mijatovic, Vladan Moilanen, Leena Montasser, May E. Morris, Andrew D. Morrison, Alanna C. Mulas, Antonella Nagaraja, Ramaiah Narisu, Narisu Nikus, Kjell O'Donnell, Christopher J. O'Reilly, Paul F. Ong, Ken K. Paccaud, Fred Palmer, Cameron D. Parsa, Afshin Pedersen, Nancy L. Penninx, Brenda W. Perola, Markus Peters, Annette Poulter, Neil Pramstaller, Peter P. Psaty, Bruce M. Quertermous, Thomas Rao, Dabeeru C. Rasheed, Asif Rayner, N. William Renstrom, Frida Rettig, Rainer Rice, Kenneth M. Roberts, Robert Rose, Lynda M. Rossouw, Jacques Samani, Nilesh J. Sanna, Serena Saramies, Jouko Schunkert, Heribert Sebert, Sylvain Sheu, Wayne H-H Shin, Young-Ah Sim, Xueling Smit, Johannes H. Smith, Albert V. Sosa, Maria X. Spector, Tim D. Stancakova, Alena Stanton, Alice V. Stirrups, Kathleen E. Stringham, Heather M. Sundstrom, Johan Swift, Amy J. Syvanen, Ann-Christine Tai, E-Shyong Tanaka, Toshiko Tarasov, Kirill V. Teumer, Alexander Thorsteinsdottir, Unnur Tobin, Martin D. Tremoli, Elena Uitterlinden, Andre G. Uusitupa, Matti Vaez, Ahmad Vaidya, Dhananjay van Duijn, Cornelia M. van Iperen, Erik P. A. Vasan, Ramachandran S. Verwoert, Germaine C. Virtamo, Jarmo Vitart, Veronique Voight, Benjamin F. Vollenweider, Peter Wagner, Aline Wain, Louise V. Wareham, Nicholas J. Watldns, Hugh Weder, Alan B. Westra, Harm Jan Wilks, Rainford Wilsgaard, Tom Wilson, James F. Wong, Tien Y. Yang, Tsun-Po Yao, Jie Yengo, Loic Zhang, Weihua Zhao, Jing Hua Zhu, Xiaofeng Bovet, Pascal Cooper, Richard S. Mohlke, Karen L. Saleheen, Danish Lee, Jong-Young Elliott, Paul Gierman, Hinco J. Willer, Cristen J. Franke, Lude Hovingh, G. Kees Taylor, Kent D. Dedoussis, George Sever, Peter Wong, Andrew Lind, Lars Assimes, Themistocles L. Njolstad, Inger Schwarz, Peter E. H. Langenberg, Claudia Snieder, Harold Caulfield, Mark J. Melander, E. Laakso, Markku Saltevo, Juha Rauramaa, Rainer Tuomilehto, Jaakko Ingelsson, Erik Lehtimaki, Terho Hveem, Kristian Palmas, Walter Marz, Winfried Kumar, Meena Salomaa, Veikko Chen, Yii-Der I. Rotter, Jerome I. Froguel, Philippe Jarvelin, Marjo-Riitta Lakatta, Edward G. Kuulasmaa, Kari Franks, Paul W. Hamsten, Anders Wichmann, H-Erich Palmer, Colin N. A. Stefansson, Kari Ridker, Paul M. Loos, Ruth J. F. Chalcravarti, Aravinda Deloukas, Panos Morris, Andrew P. Newton-Cheh, Christopher Munroe, Patricia B. CA CHARGE-EchoGen Consortium CHARGE-HF Consortium Wellcome Trust Case Control Consor TI The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; ARTERIAL-HYPERTENSION; COMMON VARIANTS; CELL-TYPES; LOCI; TRAITS; CHROMATIN; SUSCEPTIBILITY; METAANALYSIS; BIOLOGY AB To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation. C1 [Ehret, Georg B.; Pihurl, Vasyl; Arkingl, Dan E.; Sosa, Maria X.; Chalcravarti, Aravinda] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD USA. [Ehret, Georg B.; Lin, Li; Mach, Francois] Univ Hosp Geneva, Dept Med, Cardiol, Geneva, Switzerland. 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[Schunkert, Heribert] Munich Heart Alliance, Munich, Germany. [Schunkert, Heribert] Univ Oulu, Ctr Lifecourse Hlth Res, Oulu, Finland. [Sebert, Sylvain; Jarvelin, Marjo-Riitta] Natl Def Med Ctr, Coll Med, Taipei, Taiwan. Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore. Natl Univ Hlth Syst, Singapore, Singapore. [Sim, Xueling; Tai, E-Shyong] Univ Eastern Finland, Kuopio, Finland. [Sim, Xueling; Tai, E-Shyong] Kuopio Univ Hosp, Kuopio, Finland. [Stancakova, Alena] Royal Coll Surgeons Ireland, Mol & Cellular Therapeut, Dublin, Ireland. [Stanton, Alice V.] Univ Cambridge, Dept Haematol, Cambridge, England. [Stirrups, Kathleen E.] Natl Univ Singapore, Dept Med, Singapore, Singapore. [Stirrups, Kathleen E.] Natl Univ Hlth Syst, Singapore, Singapore. [Tai, E-Shyong] NIA, Intramural Res Program, Lab Cardiovasc Sci, US Natl Inst Hlth, Baltimore, MD 21224 USA. [Tarasov, Kirill V.; Lakatta, Edward G.] Univ Med Greifswald, Inst Community Med, Greifswald, Germany. [Teumer, Alexander] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England. [Tobin, Martin D.; Wain, Louise V.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Uitterlinden, Andre G.] Univ Eastern Finland, Dept Publ Hlth & Clin Nutr, Kuopio, Finland. [Uusitupa, Matti] Kuopio Univ Hosp, Res Unit, Kuopio, Finland. [Uusitupa, Matti] Isfahan Univ Med Sci, Res Inst Primordial Prevent Noncommunicable Dis, Esfahan, Iran. [Vaez, Ahmad] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Vaidya, Dhananjay] NGI Erasmus Med Ctr, Ctr Med Syst Biol CMSB 12, Rotterdam, Netherlands. [van Duijn, Cornelia M.] Acad Med Ctr, Dept Clin Epidemiol Biostat & Bioinformat, Amsterdam, Netherlands. [van Iperen, Erik P. A.] ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands. [van Iperen, Erik P. A.] Boston Univ, Dept Med, Sect Prevent Med, Sch Med, Boston, MA USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Cardiol, Boston, MA 02215 USA. [Vasan, Ramachandran S.] Univ Penn, Perelman Sch Med, Dept Genet, Dept Syst Pharmacol & Translat Therapeut, Philadelphia, PA 19104 USA. [Voight, Benjamin F.] Univ Lausanne Hosp, Dept Internal Med, Lausanne, Switzerland. [Vollenweider, Peter] Univ Strasbourg, EA3430, Dept Epidemiol & Publ Hlth, Strasbourg, France. [Wagner, Aline] Univ Michigan, Sch Med, Div Cardiovasc Med, Dept Internal Med, Ann Arbor, MI 48109 USA. [Weder, Alan B.; Willer, Cristen J.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Westra, Harm Jan] Univ West Indies, Res Inst Trop Med, Epidemiol Res Unit, Kingston, Jamaica. [Wilks, Rainford] Univ Tromso, Dept Community Med, Fac Hlth Sci, Tromso, Norway. [Wilsgaard, Tom; Njolstad, Inger] Univ Tromso, Fac Hlth Sci, Dept Clin Med, Tromso, Norway. [Wilsgaard, Tom; Njolstad, Inger] Univ Cambridge, MRC Canc Unit, Cambridge, England. [Yang, Tsun-Po] Case Western Reserve Univ, Dept Epidemiol & Biostat, Sch Med, Cleveland, OH 44106 USA. [Zhu, Xiaofeng] Minist Hlth, Victoria, Seychelles. [Bovet, Pascal] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Saleheen, Danish] Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London, England. [Elliott, Paul; Jarvelin, Marjo-Riitta] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. [Gierman, Hinco J.] Acad Med Ctr, Dept Vasc Med, Amsterdam, Netherlands. [Schwarz, Peter E. H.] Univ Hosp, Paul Langerhans Inst Dresden, Helmholtz Ctr Munich, Dresden, Germany. [Schwarz, Peter E. H.] Tech Univ Dresden, Fac Med, Dresden, Germany. [Schwarz, Peter E. H.] German Ctr Diabet Res DZD, Neuherberg, Germany. [Saltevo, Juha] Cent Finland Hlth Care Dist, Dept Med, Jyvaskyla, Finland. [Tuomilehto, Jaakko] Dasman Diabet Inst, Dasman, Kuwait. [Tuomilehto, Jaakko] King Abdulaziz Univ, Saudi Diabet Res Grp, Jeddah, Saudi Arabia. [Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria. [Palmas, Walter] Columbia Univ, Dept Med, New York, NY USA. [Marz, Winfried] Synlab Acad, Synlab Serv, Mannheim, Germany. [Marz, Winfried] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria. [Jarvelin, Marjo-Riitta] Oulu Univ Hosp, Unit Primary Care, Oulu, Finland. [Franks, Paul W.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Wichmann, H-Erich] Tech Univ Munich, Inst Med Stat & Epidemiol, Munich, Germany. [Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA. [Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth Dev Inst, New York, NY 10029 USA. [Deloukas, Panos] King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah, Saudi Arabia. [Morris, Andrew P.] Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England. RP Munroe, PB (reprint author), Queen Mary Univ London, William Harvey Res Inst, Clin Pharmacol, London, England.; Munroe, PB (reprint author), Queen Mary Univ London, NIHR Barts Cardiovasc Biomed Res Unit, London, England.; Newton-Cheh, C (reprint author), Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.; Newton-Cheh, C (reprint author), Broad Inst MIT & Harvard, Cambridge, MA USA.; Newton-Cheh, C (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. EM cnewtoncheh@mgh.harvard.edu; p.b.munroe@qmul.ac.uk RI Magnusson, Patrik/C-4458-2017; Yengo, Loic/D-2692-2017; Hicks, Andrew/E-9518-2017; BOUATIA-NAJI, NABILA/D-5863-2013; Assimes, Themistocles/D-9696-2015; Johnson, Andrew/G-6520-2013; Franke, Lude/P-7036-2016; Wong, Andrew/M-8899-2016; Shah, Sonia/N-7547-2013; Bovet, Pascal/F-4477-2011; Palmer, Colin/C-7053-2008; Peters, Annette/A-6117-2011; Vollenweider, Peter/Q-4603-2016; Deloukas, Panos/B-2922-2013; Colaus, PsyColaus/K-6607-2013 OI Evangelou, Evangelos/0000-0002-5488-2999; Vaidya, Dhananjay/0000-0002-7164-1601; Folkersen, Lasse/0000-0003-0708-9530; Tai, E Shyong/0000-0003-2929-8966; Smith, Andrew/0000-0003-1141-2978; Peters, Annette/0000-0001-6645-0985; Wain, Louise/0000-0003-4951-1867; Yengo, Loic/0000-0002-4272-9305; Hicks, Andrew/0000-0001-6320-0411; Gianfagna, Francesco/0000-0003-4615-0816; Enroth, Stefan/0000-0002-5056-9137; Bevan, Steve/0000-0003-0490-6830; Kumari, Meena/0000-0001-9716-1035; Kuulasmaa, Kari/0000-0003-2165-1411; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Assimes, Themistocles/0000-0003-2349-0009; Franke, Lude/0000-0002-5159-8802; Wong, Andrew/0000-0003-2079-4779; Shah, Sonia/0000-0001-5860-4526; Bovet, Pascal/0000-0002-0242-4259; Palmer, Colin/0000-0002-6415-6560; Vollenweider, Peter/0000-0002-0765-896X; Deloukas, Panos/0000-0001-9251-070X; FU British Heart Foundation [RG/10/12/28456, RG/13/2/30098, RG/14/5/30893]; Medical Research Council [G0401527, G0600237, G0601261, G1000143, MC_PC_U127561128, MC_UU_12013/5, MC_UU_12015/1, MC_UU_12019/1, MR/K006584/1, MR/K013351/1, MR/L01341X/1]; NCATS NIH HHS [UL1 TR000124]; NHLBI NIH HHS [R01 HL086694, R01 HL113933, R01 HL122684, T32 HL007208, T32 HL098049]; NIA NIH HHS [R01 AG025941]; NICHD NIH HHS [P2C HD050924]; NIDDK NIH HHS [P30 DK063491, U01 DK062370] NR 40 TC 9 Z9 9 U1 30 U2 30 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD OCT PY 2016 VL 48 IS 10 BP 1171 EP 1184 DI 10.1038/ng.3667 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA DX5AG UT WOS:000384391600012 PM 27618452 ER PT J AU McCarthy, S Das, S Kretzschmar, W Delaneau, O Wood, AR Teumer, A Kang, HM Fuchsberger, C Danecek, P Sharp, K Luo, Y Sidorel, C Kwong, A Timpson, N Koskinen, S Vrieze, S Scott, LJ Zhang, H Mahajan, A Veldink, J Peters, U Pato, C van Duijn, CM Gillies, CE Gandin, I Mezzavilla, M Gilly, A Cocca, M Traglia, M Angius, A Barrett, JC Boomsma, D Branham, K Breen, G Brummett, CM Busonero, F Campbell, H Chan, A Che, S Chew, E Collins, FS Corbin, LJ Smith, GD Dedoussis, G Dorr, M Farmaki, AE Ferrucci, L Forer, L Fraser, RM Gabriel, S Levy, S Groop, L Harrison, T Hattersley, A Holmen, OL Hveem, K Kretzler, M Lee, JC McGue, M Meitinger, T Melzer, D Min, JL Mohlke, KL Vincent, JB Nauck, M Nickerson, D Palotie, A Pato, M Pirastu, N McInnis, M Richards, JB Sala, C Salomaa, V Schlessinger, D Schoenherr, S Slagboom, PE Small, K Spector, T Stambolian, D Tuke, M Tuomilehto, J van den Berg, LH Van Rheenen, W Volker, U Wijmenga, C Toniolo, D Zeggini, E Gasparini, P Sampson, MG Wilson, JF Frayling, T de Bakker, PIW Swertz, MA McCarroll, S Kooperberg, C Dekker, A Altshuler, D Willer, C Iacono, W Ripatti, S Soranzo, N Walter, K Swaroop, A Cucca, F Anderson, CA Myers, RM Boehnke, M McCarthy, MI Durbin, R Abecasis, G Marchini, J AF McCarthy, Shane Das, Sayantan Kretzschmar, Warren Delaneau, Olivier Wood, Andrew R. Teumer, Alexander Kang, Hyun Min Fuchsberger, Christian Danecek, Petr Sharp, Kevin Luo, Yang Sidorel, Carlo Kwong, Alan Timpson, Nicholas Koskinen, Seppo Vrieze, Scott Scott, Laura J. Zhang, He Mahajan, Anubha Veldink, Jan Peters, Ulrike Pato, Carlos van Duijn, Cornelia M. Gillies, Christopher E. Gandin, Ilaria Mezzavilla, Massimo Gilly, Arthur Cocca, Massimiliano Traglia, Michela Angius, Andrea Barrett, Jeffrey C. Boomsma, Dorrett Branham, Kari Breen, Gerome Brummett, Chad M. Busonero, Fabio Campbell, Harry Chan, Andrew Che, Sai Chew, Emily Collins, Francis S. Corbin, Laura J. Smith, George Davey Dedoussis, George Dorr, Marcus Farmaki, Aliki-Eleni Ferrucci, Luigi Forer, Lukas Fraser, Ross M. Gabriel, Stacey Levy, Shawn Groop, Leif Harrison, Tabitha Hattersley, Andrew Holmen, Oddgeir L. Hveem, Kristian Kretzler, Matthias Lee, James C. McGue, Matt Meitinger, Thomas Melzer, David Min, Josine L. Mohlke, Karen L. Vincent, John B. Nauck, Matthias Nickerson, Deborah Palotie, Aarno Pato, Michele Pirastu, Nicola McInnis, Melvin Richards, J. Brent Sala, Cinzia Salomaa, Veikko Schlessinger, David Schoenherr, Sebastian Slagboom, P. Eline Small, Kerrin Spector, Timothy Stambolian, Dwight Tuke, Marcus Tuomilehto, Jaakko van den Berg, Leonard H. Van Rheenen, Wouter Volker, Uwe Wijmenga, Cisca Toniolo, Daniela Zeggini, Eleftheria Gasparini, Paolo Sampson, Matthew G. Wilson, James F. Frayling, Timothy de Bakker, Paul I. W. Swertz, Morris A. McCarroll, Steven Kooperberg, Charles Dekker, Annelot Altshuler, David Willer, Cristen Iacono, William Ripatti, Samuli Soranzo, Nicole Walter, Klaudia Swaroop, Anand Cucca, Francesco Anderson, Carl A. Myers, Richard M. Boehnke, Michael McCarthy, Mark I. Durbin, Richard Abecasis, Goncalo Marchini, Jonathan CA Haplotype Reference Consortium TI A reference panel of 64,976 haplotypes for genotype imputation SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; RARE VARIANTS; POPULATION; SEQUENCE AB We describe a reference panel of 64,976 human haplotypes at 39,235,157 SNPs constructed using whole-genome sequence data from 20 studies of predominantly European ancestry. Using this resource leads to accurate genotype imputation at minor allele frequencies as low as 0.1% and a large increase in the number of SNPs tested in association studies, and it can help to discover and refine causal loci. We describe remote server resources that allow researchers to carry out imputation and phasing consistently and efficiently. C1 [McCarthy, Shane; Luo, Yang; Gilly, Arthur; Barrett, Jeffrey C.; Zeggini, Eleftheria; Soranzo, Nicole; Walter, Klaudia; Anderson, Carl A.; Durbin, Richard] Wellcome Trust Sanger Inst, Human Genet, Hinxton, England. [Das, Sayantan; Kang, Hyun Min; Fuchsberger, Christian; Kwong, Alan; Scott, Laura J.; Che, Sai; Boehnke, Michael; Abecasis, Goncalo] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Das, Sayantan; Kang, Hyun Min; Fuchsberger, Christian; Kwong, Alan; Scott, Laura J.; Che, Sai; Abecasis, Goncalo] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Kretzschmar, Warren; Mahajan, Anubha; McCarthy, Mark I.; Marchini, Jonathan] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Delaneau, Olivier] Univ Geneva, Genet & Dev, Geneva, Switzerland. [Wood, Andrew R.; Tuke, Marcus; Frayling, Timothy] Univ Exeter, Sch Med, Inst Biomed Sci, Genet Complex Traits, Exeter, Devon, England. [Teumer, Alexander] Univ Med Greifswald, Inst Community Med, Greifswald, Germany. [Teumer, Alexander; Nauck, Matthias] DZHK German Ctr Cardiovasc Res, Greifswald, Germany. [Danecek, Petr] Wellcome Trust Sanger Inst, Vertebrate Resequencing Informat, Hinxton, England. [Sharp, Kevin; Marchini, Jonathan] Univ Oxford, Dept Stat, Oxford, MS USA. [Sidorel, Carlo; Angius, Andrea; Busonero, Fabio; Cucca, Francesco] CNR, IRGB, Sardinia, Italy. [Timpson, Nicholas; Corbin, Laura J.; Smith, George Davey; Min, Josine L.] Univ Bristol, MRC, Integrat Epidemiol Unit, Oakfield Grove, England. [Koskinen, Seppo; Salomaa, Veikko] THL, Helsinki, Finland. [Vrieze, Scott] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. [Vrieze, Scott] Univ Colorado, Dept Psychol & Neurosurg, Boulder, CO 80309 USA. [Zhang, He; Willer, Cristen] Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. [Veldink, Jan; van den Berg, Leonard H.; Van Rheenen, Wouter; Dekker, Annelot] Brain Ctr Rudolf Magnus, Dept Neurol & Neurosurg, Utrecht, Netherlands. [Peters, Ulrike; Harrison, Tabitha; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, 1124 Columbia St, Seattle, WA 98104 USA. [Peters, Ulrike] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Pato, Carlos; Pato, Michele] SUNY Downstate, Dept Psychiat, Brooklyn, NY USA. [van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands. [Gillies, Christopher E.; Sampson, Matthew G.] Univ Michigan, Sch Med, Dept Pediat Nephrol, Ann Arbor, MI USA. [Gandin, Ilaria; Cocca, Massimiliano; Pirastu, Nicola; Gasparini, Paolo] Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy. [Mezzavilla, Massimo] IRCCS Burlo Garofolo, Genet Med, Trieste, Italy. [Mezzavilla, Massimo; Gasparini, Paolo] Dept Expt Genet, Doha, Qatar. [Traglia, Michela; Sala, Cinzia; Toniolo, Daniela] San Raffaele Res Inst, Genet & Cell Biol, Milan, Italy. [Boomsma, Dorrett] Vrije Univ Amsterdam, Dept Biol Psychol, Netherlands Twin Register, Amsterdam, Netherlands. [Branham, Kari] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. [Breen, Gerome] Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC, Social Genet & Dev Psychiat Ctr, London, England. [Breen, Gerome] Kings Coll London, Inst Psychiat Psychol & Neurosci, NIHR Biomed Res Ctr Mental Hlth, London, England. [Breen, Gerome] South London Maudsley Hosp, London, ON, Canada. [Brummett, Chad M.; Fraser, Ross M.] Univ Michigan, Dept Anesthesiol, Ann Arbor, MI 48109 USA. [Campbell, Harry; Wilson, James F.] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland. [Chan, Andrew; Boehnke, Michael] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew; Boehnke, Michael] Harvard Med Sch, Boston, MA USA. [Chan, Andrew] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Che, Sai; Kretzler, Matthias; Willer, Cristen] Univ Michigan, Dept Computat Med, Ann Arbor, MI USA. [Che, Sai; Kretzler, Matthias; Willer, Cristen] Univ Michigan, Dept Bioinformat, Ann Arbor, MI 48109 USA. [Chew, Emily] NEI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. [Collins, Francis S.] US Natl Inst Hlth, Med Genom & Metab Genet Branch, NHGRI, Bethesda, MD USA. [Dedoussis, George; Farmaki, Aliki-Eleni] Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens, Greece. [Dorr, Marcus] Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany. [Dorr, Marcus; Nauck, Matthias; Volker, Uwe] Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Ferrucci, Luigi] Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria. [Gabriel, Stacey; Palotie, Aarno; Altshuler, David] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Levy, Shawn; Myers, Richard M.] HudsonAlpha Inst Biotechnol, Huntsville, AL USA. [Groop, Leif] Lund Univ, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden. [Groop, Leif] Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland. [Groop, Leif] Univ Helsinki, Res Programs Unit, Diabet & Obes, Helsinki, Finland. [Hattersley, Andrew] Univ Exeter, Sch Med, Inst Biomed & Clin Res, Exeter, Devon, England. [Holmen, Oddgeir L.; Hveem, Kristian] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, Hunt Res Ctr, Levanger, Norway. [Kretzler, Matthias] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. [Lee, James C.] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England. [Lee, James C.] Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, Dept Med, Cambridge, England. [McGue, Matt; Iacono, William] Univ Minnesota, Dept Psychol, Minneapolis, MN USA. [Meitinger, Thomas] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, Neuherberg, Germany. [Meitinger, Thomas] Tech Univ Munich, Inst Human Genet, Munich, Germany. [Meitinger, Thomas] Partner Site Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Munich, Germany. [Melzer, David] Univ Exeter, Sch Med, Inst Biomed & Clin Sci, Epidemiol & Publ Hlth, Exeter, Devon, England. [Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Vincent, John B.] Ctr Addict & Mental Hlth, Mol Neuropsychiat & Dev Lab, Toronto, ON, Canada. [Vincent, John B.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [Vincent, John B.] Univ Toronto, Inst Med Sci, Toronto, ON, Canada. [Nickerson, Deborah] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Palotie, Aarno] FIMM, Inst Mol Med, Helsinki, Finland. [Palotie, Aarno] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Palotie, Aarno; Altshuler, David] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Palotie, Aarno] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Palotie, Aarno] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [McInnis, Melvin] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Richards, J. Brent] McGill Univ, Dept Med, Montreal, PQ, Canada. [Richards, J. Brent] McGill Univ, Dept Human Genet, Montreal, PQ, Canada. [Richards, J. Brent; Small, Kerrin; Spector, Timothy] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England. [Schlessinger, David] US Natl Inst Hlth, Natl Inst Aging, Baltimore, MD USA. [Slagboom, P. Eline] Leiden Univ, Med Ctr, Dept Med Stat & Bioinformat, Mol Epidemiol Sect, Leiden, Netherlands. [Stambolian, Dwight] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA. [Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Chron Dis Prevent Unit, Helsinki, Finland. [Tuomilehto, Jaakko] Dasman Diabet Inst, Dasman, Kuwait. [Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria. [Tuomilehto, Jaakko] King Abdulaziz Univ, Diabet Res Grp, Jeddah, Saudi Arabia. [Volker, Uwe] Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Wijmenga, Cisca; Swertz, Morris A.] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. [Wilson, James F.] Univ Edinburgh, Western Gen Hosp, MRC, Human Genet Unit,Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland. [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Med Genet, Utrecht, Netherlands. [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Ctr Mol Med, Dept Genet, Utrecht, Netherlands. [Swertz, Morris A.] Univ Groningen, Univ Med Ctr Groningen, Genom Coordinat Ctr, Groningen, Netherlands. [McCarroll, Steven] Harvard Med Sch, Dept Genet, Boston, MA USA. [McCarroll, Steven] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Altshuler, David] Massachusetts Gen Hosp, Dept Med, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA. [Altshuler, David] Harvard Med Sch, Dept Med, Boston, MA USA. [Altshuler, David] MIT, Dept Biol, Cambridge, MA USA. [Altshuler, David] Vertex Pharmaceut, Boston, MA USA. [Ripatti, Samuli] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. [Soranzo, Nicole] Univ Cambridge, Dept Hematol, Cambridge, England. [Soranzo, Nicole] Univ Cambridge, NIHR Blood & Transplant Unit BTRU Donor Hlth Geno, Cambridge, England. [Swaroop, Anand] US Natl Inst Hlth, Neurobiol Neurodegenerat & Repair Lab, NEI, Bethesda, MD USA. [McCarthy, Mark I.] Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, MS USA. [McCarthy, Mark I.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford, England. RP Abecasis, G (reprint author), Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.; Abecasis, G (reprint author), Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.; Marchini, J (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.; Marchini, J (reprint author), Univ Oxford, Dept Stat, Oxford, MS USA. EM rd@sanger.ac.uk; marchini@stats.ox.ac.uk RI Wijmenga, Cisca/D-2173-2009; Fox, Laura /C-6249-2016; Slagboom, P. Eline/R-4790-2016; Davey Smith, George/A-7407-2013; OI Slagboom, P. Eline/0000-0002-2875-4723; Davey Smith, George/0000-0002-1407-8314; Hattersley, Andrew/0000-0001-5620-473X; Brummett, Chad/0000-0003-0974-7242; Swaroop, Anand/0000-0002-1975-1141; McCarthy, Shane/0000-0002-2715-4187; Small, Kerrin/0000-0003-4566-0005; Timpson, Nicholas/0000-0002-7141-9189 FU ERC [617306]; Wellcome Trust [WT097307, WT090851] FX We are grateful to all participants of all the studies that have contributed data to the HRC. J.M. acknowledges support from the ERC (grant 617306). W.K. acknowledges support from the Wellcome Trust (grant WT097307). S. McCarthy and R.D. acknowledge support from Wellcome Trust grant WT090851. A full list of acknowledgments for the cohorts is given in the Supplementary Note. NR 21 TC 11 Z9 11 U1 10 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD OCT PY 2016 VL 48 IS 10 BP 1279 EP 1283 DI 10.1038/ng.3643 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA DX5AG UT WOS:000384391600025 PM 27548312 ER PT J AU Das, S Forer, L Schonherr, S Sidore, C Locke, AE Kwong, A Vrieze, SI Chew, EY Levy, S McGue, M Schlessinger, D Stambolian, D Loh, PR Iacono, WG Swaroop, A Scott, LJ Cucca, F Kronenberg, F Boehnke, M Abecasis, GR Fuchsberger, C AF Das, Sayantan Forer, Lukas Schoenherr, Sebastian Sidore, Carlo Locke, Adam E. Kwong, Alan Vrieze, Scott I. Chew, Emily Y. Levy, Shawn McGue, Matt Schlessinger, David Stambolian, Dwight Loh, Po-Ru Iacono, William G. Swaroop, Anand Scott, Laura J. Cucca, Francesco Kronenberg, Florian Boehnke, Michael Abecasis, Goncalo R. Fuchsberger, Christian TI Next-generation genotype imputation service and methods SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; CORONARY-HEART-DISEASE; GENETIC-VARIATION; POPULATION; PROTECTION; MAPREDUCE; THOUSANDS AB Genotype imputation is a key component of genetic association studies, where it increases power, facilitates meta-analysis, and aids interpretation of signals. Genotype imputation is computationally demanding and, with current tools, typically requires access to a high-performance computing cluster and to a reference panel of sequenced genomes. Here we describe improvements to imputation machinery that reduce computational requirements by more than an order of magnitude with no loss of accuracy in comparison to standard imputation tools. We also describe a new web-based service for imputation that facilitates access to new reference panels and greatly improves user experience and productivity. C1 [Das, Sayantan; Sidore, Carlo; Locke, Adam E.; Kwong, Alan; Scott, Laura J.; Boehnke, Michael; Abecasis, Goncalo R.; Fuchsberger, Christian] Univ Michigan, Ctr Stat Genet, Dept Biostat, Ann Arbor, MI 48109 USA. [Forer, Lukas; Schoenherr, Sebastian; Kronenberg, Florian; Fuchsberger, Christian] Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria. [Sidore, Carlo; Cucca, Francesco] CNR, Ist Ric Genet & Biomed, Cagliari, Italy. [Sidore, Carlo; Cucca, Francesco] Univ Sassari, Dipartimento Sci Biomed, Sassari, Italy. [Vrieze, Scott I.] Univ Colorado, Inst Behav Sci, Boulder, CO 80309 USA. [Chew, Emily Y.] NEI, Clin Trials Branch, Div Epidemiol & Clin Applicat, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Levy, Shawn] HudsonAlpha Inst Biotechnol, Huntsville, AL USA. [McGue, Matt; Iacono, William G.] Univ Minnesota, Dept Psychol, Minneapolis, MN USA. [Schlessinger, David] NIA, Genet Lab, US Natl Inst Hlth, Baltimore, MD 21224 USA. [Stambolian, Dwight] Univ Penn, Dept Genet, Philadelphia, PA USA. [Loh, Po-Ru] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Loh, Po-Ru] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Fuchsberger, Christian] Univ Lubeck, European Acad Bolzano Bozen EURAC, Ctr Biomed, Bolzano, Italy. RP Abecasis, GR; Fuchsberger, C (reprint author), Univ Michigan, Ctr Stat Genet, Dept Biostat, Ann Arbor, MI 48109 USA.; Fuchsberger, C (reprint author), Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.; Fuchsberger, C (reprint author), Univ Lubeck, European Acad Bolzano Bozen EURAC, Ctr Biomed, Bolzano, Italy. EM goncalo@umich.edu; christian.fuchsberger@eurac.edu RI Kronenberg, Florian/B-1736-2008; OI Kronenberg, Florian/0000-0003-2229-1120; Locke, Adam/0000-0001-6227-198X; Swaroop, Anand/0000-0002-1975-1141 FU National Institutes of Health [HG007022, HL117626, HG000376, R01DA037904]; Austrian Science Fund (FWF) [J-3401]; European Community [602133]; Intramural Research Program of the National Institute on Aging, National Institutes of Health FX The authors gratefully acknowledge D. Hinds for assistance with minimac3 code optimizations and A.L. Williams for providing HAPI-UR. We acknowledge support from National Institutes of Health grants HG007022 and HL117626 (G.R.A.), HG000376 (M.B.), and R01DA037904 (S.I.V.), Austrian Science Fund (FWF) grant J-3401 (C.F.), and the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement 602133 (L.F. and S.S.). This work was also supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health (D. Schlessinger). NR 27 TC 5 Z9 5 U1 12 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD OCT PY 2016 VL 48 IS 10 BP 1284 EP 1287 DI 10.1038/ng.3656 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA DX5AG UT WOS:000384391600026 PM 27571263 ER PT J AU Leong, YA Chen, YP Ong, HS Wu, D Man, KV Deleage, C Minnich, M Meckiff, BJ Wei, YB Hou, ZH Zotos, D Fenix, KA Atnerkar, A Preston, S Chipman, JG Beilman, GJ Allison, CC Sun, L Wang, P Xu, JW Toe, JG Lu, HK Tao, Y Palendira, U Dent, AL Landay, AL Pellegrini, M Comerford, I McColl, SR Schacker, TW Long, HM Estes, JD Busslinger, M Belz, GT Lewin, SR Kallies, A Yu, D AF Leong, Yew Ann Chen, Yaping Ong, Hong Sheng Wu, Di Man, Kevin Deleage, Claire Minnich, Martina Meckiff, Benjamin J. Wei, Yunbo Hou, Zhaohua Zotos, Dimitra Fenix, Kevin A. Atnerkar, Anurag Preston, Simon Chipman, Jeffrey G. Beilman, Greg J. Allison, Cody C. Sun, Lei Wang, Peng Xu, Jiawei Toe, Jesse G. Lu, Hao K. Tao, Yong Palendira, Umaimainthan Dent, Alexander L. Landay, Alan L. Pellegrini, Marc Comerford, Iain McColl, Shaun R. Schacker, Timothy W. Long, Heather M. Estes, Jacob D. Busslinger, Meinrad Belz, Gabrielle T. Lewin, Sharon R. Kallies, Axel Yu, Di TI CXCR5(+) follicular cytotoxic T cells control viral infection in B cell follicles SO NATURE IMMUNOLOGY LA English DT Article ID HELPER-CELLS; VIRUS-INFECTION; HIV-INFECTION; DIFFERENTIATION; TRANSCRIPTION; BLIMP-1; EXPRESSION; EFFECTOR; TCF-1; BCL6 AB During unresolved infections, some viruses escape immunological control and establish a persistant reservoir in certain cell types, such as human immunodeficiency virus (HIV), which persists in follicular helper T cells (T-FH cells), and Epstein-Barr virus (EBV), which persists in B cells. Here we identified a specialized group of cytotoxic T cells (T-C cells) that expressed the chemokine receptor CXCR5, selectively entered B cell follicles and eradicated infected TFH cells and B cells. The differentiation of these cells, which we have called 'follicular cytotoxic T cells' (T-FC cells), required the transcription factors Bcl6, E2A and TCF-1 but was inhibited by the transcriptional regulators Blimp1, Id2 and Id3. Blimp1 and E2A directly regulated Cxcr5 expression and, together with Bcl6 and TCF-1, formed a transcriptional circuit that guided T-FC cell development. The identification of T-FC cells has far-reaching implications for the development of strategies to control infections that target B cells and T-FH cells and to treat B cell-derived malignancies. C1 [Leong, Yew Ann; Chen, Yaping; Ong, Hong Sheng; Atnerkar, Anurag; Yu, Di] Monash Univ, Monash Biomed Discovery Inst, Infect & Immun Program, Clayton, Vic, Australia. [Leong, Yew Ann; Chen, Yaping; Ong, Hong Sheng; Atnerkar, Anurag; Yu, Di] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic, Australia. [Wu, Di] Univ North Carolina Chapel Hill, Sch Dent, Chapel Hill, NC USA. [Man, Kevin; Zotos, Dimitra; Preston, Simon; Allison, Cody C.; Toe, Jesse G.; Pellegrini, Marc; Belz, Gabrielle T.; Kallies, Axel] Walter & Eliza Hall Inst Med Res, Parkville, Vic, Australia. [Man, Kevin; Zotos, Dimitra; Preston, Simon; Allison, Cody C.; Toe, Jesse G.; Pellegrini, Marc; Belz, Gabrielle T.; Kallies, Axel] Univ Melbourne, Dept Med Biol, Parkville, Vic, Australia. [Deleage, Claire; Estes, Jacob D.] Frederick Natl Lab Canc Res, Leidos Biomed Res, AIDS & Canc Virus Program, Frederick, MD USA. [Minnich, Martina; Busslinger, Meinrad] Vienna Bioctr, Res Inst Mol Pathol, Vienna, Austria. [Meckiff, Benjamin J.; Long, Heather M.] Univ Birmingham, Ctr Human Virol, Inst Immunol & Immunotherapy, Birmingham B15 2TT, W Midlands, England. [Meckiff, Benjamin J.; Long, Heather M.] Univ Birmingham, Canc Immunol & Immunotherapy Ctr, Birmingham B15 2TT, W Midlands, England. [Wei, Yunbo; Hou, Zhaohua; Yu, Di] Shandong Acad Sci, Shandong Anal & Test Ctr, Jinan, Peoples R China. [Fenix, Kevin A.; Comerford, Iain; McColl, Shaun R.] Univ Adelaide, Sch Biol Sci, Dept Mol & Cellular Biol, Adelaide, SA, Australia. [Chipman, Jeffrey G.; Beilman, Greg J.] Univ Minnesota, Dept Surg, Box 242 UMHC, Minneapolis, MN 55455 USA. [Sun, Lei; Wang, Peng] Capital Med Univ, Beijing Ditan Hosp, Dept Pathol, Beijing, Peoples R China. [Xu, Jiawei] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Biostat, Chapel Hill, NC USA. [Lu, Hao K.; Lewin, Sharon R.] Univ Melbourne, Peter Doherty Inst Infect & Immun, Melbourne, Vic, Australia. [Lu, Hao K.; Lewin, Sharon R.] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Tao, Yong] Capital Med Univ, Beijing Chaoyang Hosp, Dept Ophthalmol, Beijing, Peoples R China. [Palendira, Umaimainthan] Centenary Inst, Newtown, Tas, Australia. [Dent, Alexander L.] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. [Landay, Alan L.] Rush Univ, Med Ctr, Dept Immunol Microbiol, Chicago, IL 60612 USA. [Schacker, Timothy W.] Univ Minnesota, Dept Med, Box 736 UMHC, Minneapolis, MN 55455 USA. [Lewin, Sharon R.] Monash Univ, Alfred Hosp, Dept Infect Dis, Melbourne, Vic, Australia. [Yu, Di] Monash Univ, Sch Clin Sci, Ctr Inflammatory Dis, Clayton, Vic, Australia. RP Yu, D (reprint author), Monash Univ, Monash Biomed Discovery Inst, Infect & Immun Program, Clayton, Vic, Australia.; Yu, D (reprint author), Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic, Australia.; Kallies, A (reprint author), Walter & Eliza Hall Inst Med Res, Parkville, Vic, Australia.; Kallies, A (reprint author), Univ Melbourne, Dept Med Biol, Parkville, Vic, Australia.; Yu, D (reprint author), Shandong Acad Sci, Shandong Anal & Test Ctr, Jinan, Peoples R China.; Yu, D (reprint author), Monash Univ, Sch Clin Sci, Ctr Inflammatory Dis, Clayton, Vic, Australia. EM kallies@wehi.edu.au; di.yu@monash.edu RI Yu, Di/C-2163-2009; OI Yu, Di/0000-0003-1721-8922; Hou, Zhaohua/0000-0003-3093-0279; Busslinger, Meinrad/0000-0002-9111-9351 FU Birmingham Science City - Experimental Medicine Network of Excellence project; National Health and Medical Research Council of Australia [GNT1085509, GNT1085151]; Monash University; amfAR Research Consortium on HIV Eradication [109327-59-RGRL]; Creative and Novel Ideas in HIV Research Program of The International AIDS Society; Australian Centre for HIV and Hepatitis Virology Research [2015-69]; Priority Research Program of Shandong Academy of Sciences; Shandong Province Taishan Scholar Program; Sylvia and Charles Viertel Foundation; Delaney AIDS Research Enterprise; Martin Delaney Collaboratories; National Institute for Allergy and Infectious Diseases of the US National Institutes of Health [U19 AI096109]; Bloodwise, UK [15021]; National Cancer Institute of the US National Institutes of Health [HHSN261200800001E]; Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institute Infrastructure Support scheme FX We acknowledge the facilities, scientific and technical assistance of Flowcore, Monash Micro Imaging, and Monash Bioinformatics Platform (S. Archer and K. Tsyganov) at Monash University, and University of Birmingham's Human Biomaterials Resource Centre (supported through Birmingham Science City - Experimental Medicine Network of Excellence project). We thank L. Ye (Third Military Medical University) for Thy1.1 reporter constructs; C. Vinuesa (Australian National University) and S. Nutt (Walter and Eliza Hall Institute of Medical Research) for mice; R. Gloury and L. Mackiewicz for technical support; C. Dong for the list of Bcl6-bound genes; and H. Xue for the list of TCF-1-bound genes. Supported by the National Health and Medical Research Council of Australia (Y.A.L. and S.R.L.; GNT1085509 to D.Y.; and GNT1085151 to A.K.), Monash University (D.Y.), the amfAR Research Consortium on HIV Eradication (109327-59-RGRL, D.Y., S. R. L. and A. L. L.), The Creative and Novel Ideas in HIV Research Program of The International AIDS Society (D.Y.), Australian Centre for HIV and Hepatitis Virology Research (2015-69 to D.Y.), The Priority Research Program of Shandong Academy of Sciences (D.Y.), Shandong Province Taishan Scholar Program (D.Y.), the Sylvia and Charles Viertel Foundation (A.K.), the Delaney AIDS Research Enterprise to find a cure, Martin Delaney Collaboratories, the National Institute for Allergy and Infectious Diseases of the US National Institutes of Health (U19 AI096109 to S.R.L., T.W.S. and J.D.E.), Bloodwise, UK (15021 to H.M.L. and B.J.M.), the National Cancer Institute of the US National Institutes of Health (HHSN261200800001E), and the Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institute Infrastructure Support scheme. 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 US Government. NR 62 TC 12 Z9 12 U1 6 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 EI 1529-2916 J9 NAT IMMUNOL JI Nat. Immunol. PD OCT PY 2016 VL 17 IS 10 BP 1187 EP + DI 10.1038/ni.3543 PG 13 WC Immunology SC Immunology GA DX3VD UT WOS:000384302900010 PM 27487330 ER PT J AU Garcia-Cossio, E Witkowski, M Robinson, SE Cohen, LG Birbaumer, N Soekadar, SR AF Garcia-Cossio, Eliana Witkowski, Matthias Robinson, Stephen E. Cohen, Leonardo G. Birbaumer, Niels Soekadar, Surjo R. TI Simultaneous transcranial direct current stimulation (tDCS) and whole-head magnetoencephalography (MEG): assessing the impact of tDCS on slow cortical magnetic fields SO NEUROIMAGE LA English DT Article DE Transcranial direct current stimulation; Magnetoencephalography; Slow cortical fields; Source-reconstruction ID NONINVASIVE BRAIN-STIMULATION; CONTINGENT NEGATIVE-VARIATION; MOTOR CORTEX; NEURONAL-ACTIVITY; NETWORK DYNAMICS; EEG FLUCTUATIONS; HUMANS; EXCITABILITY; FMRI; POTENTIALS AB Transcranial direct current stimulation (tDCS) can influence cognitive, affective or motor brain functions. Whereas previous imaging studies demonstrated widespread tDCS effects on brain metabolism, direct impact of tDCS on electric or magnetic source activity in task-related brain areas could not be confirmed due to the difficulty to record such activity simultaneously during tDCS. The aim of this proof-of-principal study was to demonstrate the feasibility of whole-head source localization and reconstruction of neuromagnetic brain activity during tDCS and to confirm the direct effect of tDCS on ongoing neuromagnetic activity in task-related brain areas. Here we show for the first time that tDCS has an immediate impact on slow cortical magnetic fields (SCF, 0-4 Hz) of task-related areas that are identical with brain regions previously described in metabolic neuroimaging studies. 14 healthy volunteers performed a choice reaction time (RT) task while whole-head magnetoencephalography (MEG) was recorded. Task-related source-activity of SCFs was calculated using synthetic aperture magnetometry (SAM) in absence of stimulation and while anodal, cathodal or sham tDCS was delivered over the right primary motor cortex (M1). Source reconstruction revealed task-related SCF modulations in brain regions that precisely matched prior metabolic neuroimaging studies. Anodal and cathodal tDCS had a polarity-dependent impact on RT and SCF in primary sensorimotor and medial centro-parietal cortices. Combining tDCS and whole-head MEG is a powerful approach to investigate the direct effects of transcranial electric currents on ongoing neuromagnetic source activity, brain function and behavior. (C) 2015 Elsevier Inc. All rights reserved. C1 [Garcia-Cossio, Eliana; Witkowski, Matthias; Birbaumer, Niels; Soekadar, Surjo R.] Univ Tubingen, Inst Med Psychol & Behav Neurobiol, D-72076 Tubingen, Germany. [Garcia-Cossio, Eliana; Witkowski, Matthias; Birbaumer, Niels; Soekadar, Surjo R.] Univ Tubingen, MEG Ctr, D-72076 Tubingen, Germany. [Garcia-Cossio, Eliana; Witkowski, Matthias; Soekadar, Surjo R.] Univ Tubingen, Dept Psychiat & Psychotherapy, Appl Neurotechnol Lab, D-72076 Tubingen, Germany. [Garcia-Cossio, Eliana] Radboud Univ Nijmegen, Dept Artificial Intelligence, Donders Ctr Brain Cognit & Behav, Nijmegen, Netherlands. [Robinson, Stephen E.] NIMH, NIH, MEG Core Facil, Bethesda, MD 20892 USA. [Cohen, Leonardo G.] NINDS, NIH, Human Cort Physiol & Stroke Neurorehabil Sect, Bethesda, MD 20892 USA. [Birbaumer, Niels] Osped San Camillo, Ist Ricovero & Cura Carattere Sci, I-30126 Venice, Italy. RP Soekadar, SR (reprint author), Univ Tubingen, Calwerstr 14, D-72076 Tubingen, Germany. EM surjo.soekadar@uni-tuebingen.de FU Intramural Research Program (IRP) of the National Institute of Neurological Disorders and Stroke (NINDS); National Institute of Mental Health (NIMH), Bethesda, Maryland, USA; German Federal Ministry of Education and Research (BMBF, Foderzeichen) [01GQ0831, 16SV5840]; Deutsche Forschungsgemeinschaft (DFG) [SO932-2]; European Union [FP7-ICT-2011-288551, AIDE 645322]; DAAD (Deutscher Akademischer Austauschdienst); fortune Program of the University of Tubingen's Medical Faculty [2216-0-0/ F-No. 1331418]; Brain Products GmbH; Volkswagenstiftung FX This work was supported by the Intramural Research Program (IRP) of the National Institute of Neurological Disorders and Stroke (NINDS) and National Institute of Mental Health (NIMH), Bethesda, Maryland, USA, the German Federal Ministry of Education and Research (BMBF, Foderzeichen 01GQ0831, 16SV5840), the Deutsche Forschungsgemeinschaft (DFG SO932-2), the European Union (FP7-ICT-2011-288551, Horizon 2020: AIDE 645322) and DAAD (Deutscher Akademischer Austauschdienst), fortune Program of the University of Tubingen's (No. 2216-0-0/ F-No. 1331418) Medical Faculty, the Brain Products GmbH and Volkswagenstiftung. All authors reported no financial interests or potential conflicts of interest. NR 59 TC 6 Z9 6 U1 12 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD OCT PY 2016 VL 140 BP 33 EP 40 DI 10.1016/j.neuroimage.2015.09.068 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA DX0RK UT WOS:000384071900004 PM 26455796 ER PT J AU Witkowski, M Garcia-Cossio, E Chander, BS Braun, C Birbaumer, N Robinson, SE Soekadar, SR AF Witkowski, Matthias Garcia-Cossio, Eliana Chander, Bankim S. Braun, Christoph Birbaumer, Niels Robinson, Stephen E. Soekadar, Surjo R. TI Mapping entrained brain oscillations during transcranial alternating current stimulation (tACS) SO NEUROIMAGE LA English DT Article DE Neuromagnetic brain oscillations; Entrainment; Transcranial alternating current stimulation; Whole-head magnetoencephalography ID ELECTRICAL-STIMULATION; IN-VIVO; CORTEX; PERFORMANCE; RESPONSES; STIMULUS; NEURONS; RECORDINGS; PLASTICITY; RESONANCE AB Transcranial alternating current stimulation (tACS), a non-invasive and well-tolerated form of electric brain stimulation, can influence perception, memory, as well as motor and cognitive function. While the exact underlying neurophysiological mechanisms are unknown, the effects of tACS are mainly attributed to frequency-specific entrainment of endogenous brain oscillations in brain areas close to the stimulation electrodes, and modulation of spike timing dependent plasticity reflected in gamma band oscillatory responses. tACS-related electromagnetic stimulator artifacts, however, impede investigation of these neurophysiological mechanisms. Here we introduce a novel approach combining amplitude-modulated tACS during whole-head magnetoencephalography (MEG) allowing for artifact-free source reconstruction and precise mapping of entrained brain oscillations underneath the stimulator electrodes. Using this approach, we show that reliable reconstruction of neuromagnetic low and high-frequency oscillations including high gamma band activity in stimulated cortical areas is feasible opening a new window to unveil the mechanisms underlying the effects of stimulation protocols that entrain brain oscillatory activity. (C) 2015 Elsevier Inc. All rights reserved. C1 [Witkowski, Matthias; Garcia-Cossio, Eliana; Chander, Bankim S.; Soekadar, Surjo R.] Univ Tubingen Hosp, Dept Psychiat & Psychotherapy, Appl Neurotechnol Lab, Calwerstr 14, D-72076 Tubingen, Germany. [Garcia-Cossio, Eliana; Birbaumer, Niels; Soekadar, Surjo R.] Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Tubingen, Germany. [Garcia-Cossio, Eliana] Radboud Univ Nijmegen, Dept Artificial Intelligence, Donders Ctr Brain Cognit & Behav, Nijmegen, Netherlands. [Braun, Christoph] Univ Tubingen, MEG Ctr, Tubingen, Germany. [Braun, Christoph] Univ Trento, Ctr Mind Brain Sci, CIMeC, Trento, Italy. [Robinson, Stephen E.] NIMH, MEG Core Facil, Bethesda, MD 20892 USA. RP Soekadar, SR (reprint author), Univ Tubingen Hosp, Dept Psychiat & Psychotherapy, Appl Neurotechnol Lab, Calwerstr 14, D-72076 Tubingen, Germany. EM surjo.soekadar@uni-tuebingen.de NR 54 TC 7 Z9 7 U1 14 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD OCT PY 2016 VL 140 BP 89 EP 98 DI 10.1016/j.neuroimage.2015.10.024 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA DX0RK UT WOS:000384071900011 PM 26481671 ER PT J AU Forthun, I Wilcox, AJ Strandberg-Larsen, K Moster, D Nohr, EA Lie, RT Suren, P Tollanes, MC AF Forthun, Ingeborg Wilcox, Allen J. Strandberg-Larsen, Katrine Moster, Dag Nohr, Ellen A. Lie, Rolv Terje Suren, Pal Tollanes, Mette C. TI Maternal Prepregnancy BMI and Risk of Cerebral Palsy in Offspring SO PEDIATRICS LA English DT Article ID AUTISM SPECTRUM DISORDERS; MEDICAL BIRTH REGISTRY; FOLIC-ACID SUPPLEMENTS; OBESITY; COHORT; CHILDREN; SURVEILLANCE; INFLAMMATION; METAANALYSIS; PREVALENCE AB OBJECTIVES: To investigate the association between maternal pre-pregnancy BMI and risk of cerebral palsy (CP) in offspring. METHODS: The study population consisted of 188 788 children in the Mothers and Babies in Norway and Denmark CP study, using data from 2 population-based, prospective birth cohorts: the Norwegian Mother and Child Cohort Study and the Danish National Birth Cohort. Prepregnancy BMI was classified as underweight (BMI <18.5), lower normal weight (BMI 18.5-22.9), upper normal weight (BMI 23.0-24.9), overweight (BMI 25.0-29.9), and obese (BMI >= 30). CP diagnoses were obtained from the national CP registries. Associations between maternal prepregnancy BMI and CP in offspring were investigated by using log-binomial regression models. RESULTS: The 2 cohorts had 390 eligible cases of CP (2.1 per 1000 live-born children). Compared with mothers in the lower normal weight group, mothers in the upper normal group had a 40% excess risk of having a child with CP (relative risk [RR], 1.35; 95% confidence interval [CI], 1.03-1.78). Excess risk was 60% (RR, 1.56; 95% CI, 1.21-2.01) for overweight mothers and 60% (RR, 1.55; 95% CI 1.11-2.18) for obese mothers. The risk of CP increased similar to 4% for each unit increase in BMI (RR, 1.04; 95% CI, 1.02-1.06). Estimates changed little with adjustment for mother's occupational status, age, and smoking habits. CONCLUSIONS: Higher prepregnancy maternal BMI was associated with increased risk of CP in offspring. C1 [Forthun, Ingeborg; Moster, Dag; Lie, Rolv Terje; Tollanes, Mette C.] Univ Bergen, Dept Global Publ Hlth & Primary Care, PB 7804, N-5020 Bergen, Norway. [Forthun, Ingeborg; Moster, Dag] Haukeland Hosp, Dept Pediat, Bergen, Norway. [Wilcox, Allen J.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Durham, NC USA. [Strandberg-Larsen, Katrine] Univ Copenhagen, Dept Publ Hlth, Sect Social Med, Copenhagen, Denmark. [Moster, Dag; Suren, Pal; Tollanes, Mette C.] Norwegian Inst Publ Hlth, Oslo, Norway. [Nohr, Ellen A.] Univ Southern Denmark, Inst Clin Res, Res Unit Gynaecol & Obstet, Odense, Denmark. RP Forthun, I (reprint author), Univ Bergen, Dept Global Publ Hlth & Primary Care, PB 7804, N-5020 Bergen, Norway. EM ingeborg.forthun@uib.no OI Wilcox, Allen/0000-0002-3376-1311 FU Norwegian Ministry of Health; Norwegian Ministry of Education and Research; National Institutes of Health (NIH)/National Institute of Environmental Health Sciences [N01-ES-75558]; NIH/National Institute of Neurological Disorders and Stroke [U01 NS 047537-01, U01 NS 047537-06A1]; Pharmacy Foundation; Egmont Foundation; March of Dimes Birth Defects Foundation; Augustinus Foundation; Health Foundation; Western Norwegian Regional Health Authority; Intramural Research Program at the National Institute of Environmental Health Sciences, NIH; Norwegian Institute of Public Health; University of Copenhagen; Aarhus University; National Institutes of Health (NIH) FX The Norwegian Mother and Child Cohort Study is supported by the Norwegian Ministry of Health and the Ministry of Education and Research, the National Institutes of Health (NIH)/National Institute of Environmental Health Sciences (contract N01-ES-75558), NIH/National Institute of Neurological Disorders and Stroke (grants U01 NS 047537-01 and U01 NS 047537-06A1). The Danish National Research Foundation has established the Danish Epidemiology Science Centre that initiated and created the Danish National Birth Cohort. The cohort is furthermore a result of a major grant from this foundation. Additional support for the Danish National Birth Cohort is obtained from the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, the Augustinus Foundation, and the Health Foundation. The analyses presented in this article were funded by the Western Norwegian Regional Health Authority and by the Intramural Research Program at the National Institute of Environmental Health Sciences, NIH. In addition, the Norwegian Institute of Public Health, the University of Copenhagen, and Aarhus University contributed to the funding by paying for data files and linkage to registries, and providing administrative support. Funded by the National Institutes of Health (NIH). NR 35 TC 1 Z9 1 U1 7 U2 7 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD OCT PY 2016 VL 138 IS 4 AR e20160874 DI 10.1542/peds.2016-0874 PG 9 WC Pediatrics SC Pediatrics GA DX3ZT UT WOS:000384317700031 ER PT J AU Li, KG Haynie, D Lipsky, L Iannotti, RJ Pratt, C Simons-Morton, B AF Li, Kaigang Haynie, Denise Lipsky, Leah Iannotti, Ronald J. Pratt, Charlotte Simons-Morton, Bruce TI Changes in Moderate-to-Vigorous Physical Activity Among Older Adolescents SO PEDIATRICS LA English DT Article ID SEDENTARY BEHAVIOR; UNITED-STATES; PATTERNS; TRANSITION; OVERWEIGHT; ADULTHOOD; CHILDREN; WEIGHT; YOUTH; GIRLS AB OBJECTIVES: Examined patterns and determinants of objectively measured moderate-to-vigorous physical activity (MVPA) over 4 years in US emerging adults. METHODS: Waves 1 through 4 (W1 [10th grade] to W4 data of a national cohort starting in 2010 (N = 561; 16.19 +/- 0.51 years) were used. MVPA was assessed annually from accelerometers; BMI calculated from measured height/weight; and surveys ascertained self-reported physical activity (PA) planning, peer PA, family support, W1 sociodemographics, W4 school status, W4 residence, and W4 employment. Latent growth modeling estimated trajectories in log-transformed duration (minutes/day) of MVPA and associations with covariates. RESULTS: Less than 9% of participants met the recommended 60+ minutes/day MVPA across W1 through W4. W1 MVPA was greater in males versus females (B = 0.46, P < .001) and Hispanic versus White (B = 0.34, P < .001) participants. Increased BMI change (W1 to W4 slope) was associated with decreased MVPA. MVPA was positively associated with PA planning (W1-W3: B = 0.10, B = 0.06, B = 0.08, Ps < .05), but not with peer PA or family support. Participants attending 4-year college versus not-attending school (B = 0.52, P < .001), and college students living on campus versus at home (B = 0.37, P < .001) were more likely to engage in MVPA at W4. Weekend MVPA remained relatively constant from W1 through W4. CONCLUSIONS: High-school students engaged in little MVPA and maintained this low level through the transition to adulthood. Emerging adults' MVPA engagement may vary according to social contexts. Those with high BMI may benefit most from interventions to promote MVPA. C1 [Li, Kaigang] Colorado State Univ, Dept Hlth & Exercise Sci, B 215E Moby Complex, Ft Collins, CO 80523 USA. [Haynie, Denise; Lipsky, Leah; Simons-Morton, Bruce] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Bethesda, MD USA. [Iannotti, Ronald J.] CDM Grp Inc, Bethesda, MD USA. [Pratt, Charlotte] NHLBI, Div Cardiovasc Sci, Bldg 10, Bethesda, MD 20892 USA. RP Li, KG (reprint author), Colorado State Univ, Dept Hlth & Exercise Sci, B 215E Moby Complex, Ft Collins, CO 80523 USA. EM kaigang.li@colostate.edu RI Dey, Kamalesh/E-6568-2017; OI Simons-Morton, Bruce/0000-0003-1099-6617; Haynie, Denise/0000-0002-8270-6079; Lipsky, Leah/0000-0003-2645-4388 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development [HHSN275201200001I]; National Heart, Lung, and Blood Institute; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Maternal and Child Health Bureau of the Health Resources and Services Administration; National Institutes of Health (NIH) FX This project (contract HHSN275201200001I) was supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the National Heart, Lung, and Blood Institute; the National Institute on Alcohol Abuse and Alcoholism; the National Institute on Drug Abuse; and the Maternal and Child Health Bureau of the Health Resources and Services Administration. Funded by the National Institutes of Health (NIH). NR 36 TC 0 Z9 0 U1 9 U2 9 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD OCT PY 2016 VL 138 IS 4 AR e20161372 DI 10.1542/peds.2016-1372 PG 10 WC Pediatrics SC Pediatrics GA DX3ZT UT WOS:000384317700042 ER PT J AU Sheftall, AH Asti, L Horowitz, LM Felts, A Fontanella, CA Campo, JV Bridge, JA AF Sheftall, Arielle H. Asti, Lindsey Horowitz, Lisa M. Felts, Adrienne Fontanella, Cynthia A. Campo, John V. Bridge, Jeffrey A. TI Suicide in Elementary School-Aged Children and Early Adolescents SO PEDIATRICS LA English DT Article ID DEATH REPORTING SYSTEM; PREVENTION PROGRAM; COMPLETED SUICIDE; PRIMARY-CARE; YOUTH SUICIDE; RISK-FACTORS; 16 STATES; BEHAVIOR; CHILDHOOD; INTERVENTIONS AB BACKGROUND AND OBJECTIVES: Suicide in elementary school-aged children is not well studied, despite a recent increase in the suicide rate among US black children. The objectives of this study were to describe characteristics and precipitating circumstances of suicide in elementary school-aged children relative to early adolescent decedents and identify potential within-group racial differences. METHODS: We analyzed National Violent Death Reporting System (NVDRS) surveillance data capturing suicide deaths from 2003 to 2012 for 17 US states. Participants included all suicide decedents aged 5 to 14 years (N = 693). Age group comparisons (5-11 years and 12-14 years) were conducted by using the chi(2) test or Fisher's exact test, as appropriate. RESULTS: Compared with early adolescents who died by suicide, children who died by suicide were more commonly male, black, died by hanging/strangulation/suffocation, and died at home. Children who died by suicide more often experienced relationship problems with family members/friends (60.3% vs 46.0%; P = .02) and less often experienced boyfriend/girlfriend problems (0% vs 16.0%; P < .001) or left a suicide note (7.7% vs 30.2%; P < .001). Among suicide decedents with known mental health problems (n = 210), childhood decedents more often experienced attention-deficit disorder with or without hyperactivity (59.3% vs 29.0%; P = .002) and less often experienced depression/dysthymia (33.3% vs 65.6%; P = .001) compared with early adolescent decedents. CONCLUSIONS: These findings raise questions about impulsive responding to psychosocial adversity in younger suicide decedents, and they suggest a need for both common and developmentally-specific suicide prevention strategies during the elementary school-aged and early adolescent years. Further research should investigate factors associated with the recent increase in suicide rates among black children. C1 [Sheftall, Arielle H.; Felts, Adrienne; Bridge, Jeffrey A.] Ohio State Univ, Coll Med, Res Inst, Nationwide Childrens Hosp, Columbus, OH 43210 USA. [Fontanella, Cynthia A.; Campo, John V.] Ohio State Univ, Coll Med, Dept Psychiat, Columbus, OH 43210 USA. [Bridge, Jeffrey A.] Ohio State Univ, Coll Med, Dept Pediat, Columbus, OH 43210 USA. [Asti, Lindsey] Johns Hopkins Univ, Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. [Horowitz, Lisa M.] NIMH, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Bridge, JA (reprint author), Nationwide Childrens Hosp, Res Inst, Ctr Innovat Pediat Practice, 700 Childrens Dr, Columbus, OH 43205 USA. EM jeff.bridge@nationwidechildrens.org FU National Institute of Mental Health, National Institutes of Health [R01-MH093552]; Centers for Disease Control and Prevention [R01-CE002129]; National Institutes of Health (NIH) FX All phases of the study were supported by grant R01-MH093552 from the National Institute of Mental Health, National Institutes of Health, and grant R01-CE002129 from the Centers for Disease Control and Prevention. Supported by the National Institutes of Health (NIH). NR 55 TC 0 Z9 0 U1 14 U2 14 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD OCT PY 2016 VL 138 IS 4 AR e20160436 DI 10.1542/peds.2016-0436 PG 10 WC Pediatrics SC Pediatrics GA DX3ZT UT WOS:000384317700021 ER PT J AU Calogero, JP Frecker, MI Hasnain, Z Hubbard, JE AF Calogero, J. P. Frecker, M. I. Hasnain, Z. Hubbard, J. E., Jr. TI A dynamic spar numerical model for passive shape change SO SMART MATERIALS AND STRUCTURES LA English DT Article DE contact-aided compliant mechanism; passive shape change; flapping wing morphing; constraint dynamics ID COMPLIANT MECHANISMS; WINGS; DESIGN AB A three-dimensional constraint-driven dynamic rigid-link numerical model of a flapping wing structure with compliant joints (CJs) called the dynamic spar numerical model is introduced and implemented. CJs are modeled as spherical joints with distributed mass and spring-dampers with coupled nonlinear spring and damping coefficients, which models compliant mechanisms spatially distributed in the structure while greatly reducing computation time compared to a finite element model. The constraints are established, followed by the formulation of a state model used in conjunction with a forward time integrator, an experiment to verify a rigid-link assumption and determine a flapping angle function, and finally several example runs. Modeling the CJs as coupled bi-linear springs shows the wing is able to flex more during upstroke than downstroke. Coupling the spring stiffnesses allows an angular deformation about one axis to induce an angular deformation about another axis, where the magnitude is proportional to the coupling term. Modeling both the leading edge and diagonal spars shows that the diagonal spar changes the kinematics of the leading edge spar verses only considering the leading edge spar, causing much larger axial rotations in the leading edge spar. The kinematics are very sensitive to CJ location, where moving the CJ toward the wing root causes a stronger response, and adding multiple CJs on the leading edge spar with a CJ on the diagonal spar allows the wing to deform with larger magnitude in all directions. This model lays a framework for a tool which can be used to understand flapping wing flight. C1 [Calogero, J. P.; Frecker, M. I.] Penn State Univ, Dept Mech & Nucl Engn, University Pk, PA 16802 USA. [Hasnain, Z.; Hubbard, J. E., Jr.] Univ Maryland, Dept Aerosp Engn, Hampton, VA USA. [Hasnain, Z.; Hubbard, J. E., Jr.] NIA, Hampton, VA USA. RP Calogero, JP (reprint author), Penn State Univ, Dept Mech & Nucl Engn, University Pk, PA 16802 USA. EM jc7@psu.edu FU Air Force Office of Scientific Research (AFOSR) [FA9550-13-0126] FX The authors gratefully acknowledge the support of the Air Force Office of Scientific Research (AFOSR), grant number FA9550-13-0126 under the direction of Dr David Stargel. We would like to thank James Lankford and Kaleb Bordner from the Alfred Gessow Rotorcraft Center at The University of Maryland for allowing us to use their facility and aiding us in the experiment. The resources of the NASA Langley Research Center, The Pennsylvania State University, University of Maryland and Morpheus Lab are also appreciated. The first author would like to acknowledge Dr H J Sommer for helping to understand the forward dynamic constraint method. NR 48 TC 0 Z9 0 U1 4 U2 4 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0964-1726 EI 1361-665X J9 SMART MATER STRUCT JI Smart Mater. Struct. PD OCT PY 2016 VL 25 IS 10 AR 104006 DI 10.1088/0964-1726/25/10/104006 PG 16 WC Instruments & Instrumentation; Materials Science, Multidisciplinary SC Instruments & Instrumentation; Materials Science GA DX0XG UT WOS:000384089200006 ER PT J AU Miller, S Suppes, T Mintz, J Hellemann, G Frye, MA McElroy, SL Nolen, WA Kupka, R Leverich, GS Grunze, H Altshuler, LL Keck, PE Post, RM AF Miller, Shefali Suppes, Trisha Mintz, Jim Hellemann, Gerhard Frye, Mark A. McElroy, Susan L. Nolen, Willem A. Kupka, Ralph Leverich, Gabriele S. Grunze, Heinz Altshuler, Lori L. Keck, Paul E., Jr. Post, Robert M. TI Mixed Depression in Bipolar Disorder: Prevalence Rate and Clinical Correlates During Naturalistic Follow-Up in the Stanley Bipolar Network SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID MANIC SYMPTOMS; AGITATED DEPRESSION; STATE; EPISODES; SYMPTOMATOLOGY; PHENOMENOLOGY; INVENTORY; DIAGNOSIS AB Objective: DSM-5 introduced the "with mixed features" specifier for major depressive episodes. The authors assessed the prevalence and phenomenology of mixed depression among bipolar disorder patients and qualitatively compared a range of diagnostic thresholds for mixed depression. Method: In a naturalistic study, 907 adult outpatients with bipolar disorder participating in the Stanley Foundation Bipolar Network were followed longitudinally across 14,310 visits from 1995 to 2002. The Inventory of Depressive Symptomatology-Clinician-Rated Version (IDS-C) and the Young Mania Rating Scale (YMRS) were administered at each visit. Results: Mixed depression, defined as an IDS-C score >= 15 and a YMRS score >2 and <12 at the same visit, was observed in 2,139 visits (14.9% of total visits, and 43.5% of visits with depression) by 584 patients (64.4% of all patients). Women were significantly more Likely than men to experience subthreshold hypomania during visits with depression (40.7% compared with 34.4%). Patients with one or more mixed depression visits had more symptomatic visits and fewer euthymic visits compared with those with no mixed depression visits. DSM-5-based definitions of mixed depression (ranging from narrower definitions requiring >= 3 non overlapping YMRS items concurrent with an IDS-C score >= 15 to broader definitions requiring >= 2 nonoverlapping YMRS items) yielded lower mixed depression prevalence rates (6.3% and 10.8% of visits, respectively) but were found to have similar relationships to gender and longitudinal symptom severity. Conclusions: Among outpatients with bipolar disorder, concurrent hypomanic symptoms observed during visits with depression were common, particularly in women. The DSM-5 diagnostic criteria for depression with mixed features may yield inadequate sensitivity to detect patients with mixed depression. C1 [Miller, Shefali] VA Pato Alto Hlth Care Syst, Palo Alto, CA 94304 USA. Stanford Univ, Med Ctr, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. Mayo Clin, Dept Psychiat, Rochester, MN USA. Univ Cincinnati, Lindner Ctr HOPE, Mason, OH USA. Univ Groningen, Univ Med Ctr Groningen, NL-9700 AB Groningen, Netherlands. Altrecht Inst Mental Hlth Care, Utrecht, Netherlands. Vrije Univ Amsterdam, VU Univ Med Ctr Amsterdam, Amsterdam, Netherlands. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Paracelsus Med Univ, Dept Psychiat & Psychotherapy, Salzburg, Austria. Christian Doppler Klin, Salzburg, Austria. George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA. RP Miller, S (reprint author), VA Pato Alto Hlth Care Syst, Palo Alto, CA 94304 USA. EM shefalis@stanford.edu OI Grunze, Heinz/0000-0003-4712-8979 FU Stanley Medical Research Institute; Merck; Sunovion; AztraZeneca; H Lundbeck; Elan Pharma International; NIMH; VA Cooperative Studies Program; AssureRx Health; Janssen; Mayo Foundation; Myriad; National Institute on Alcohol Abuse and Alcoholism; Pfizer; Agency for Heatthcare Research and Quality; Alkermes; AstraZeneca; Cephalon; Eli Lilly; Forest; Marriott Foundation; Naurex; Orexigen; Shire; Takeda; Transcept; Johnson Johnson; National Institute for Health Research; Medical Research Council; Northumberland; Tyne; Wear National Health Service Foundation Trust; Otsuka Pharmaceuticals; American College of Psychiatrists; GlaxoSmithKline; Ferrer; Janssen-Cilag; Lundbeck; Otsuka; Servier FX Grant support was provided by the Stanley Medical Research Institute.; Dr. Miller has received grant support from Merck and Sunovion. Dr. Suppes has received consulting fees from AztraZeneca, H Lundbeck, Merck, and Sunovion; she has received research funding from Elan Pharma International, NIMH, Sunovion, and the VA Cooperative Studies Program; and she has received royalties from Jones and Bartlett and UpToDate. Dr. Frye has received grant support from AssureRx Health, Janssen, the Mayo Foundation, Myriad, the National Institute on Alcohol Abuse and Alcoholism, NIMH, and Pfizer; he has been a consultant to Janssen, Mitsubishi Tanabe Pharma, Myriad Genetics, Sunovion, Supernus, and Teva; and he has received CME and travel support from CME Outfitters and the American Psychiatric Association. Dr. McElroy is a consultant to or member of scientific advisory boards of Alkermes, Bracket, Corcept, Hoffmann-La Roche, MedAvante, Naurex, Novo Nordisk, Shire, Sunovion, and Teva; she is a principal or coinvestigator on studies sponsored by the Agency for Heatthcare Research and Quality, Alkermes, AstraZeneca, Cephalon, Eli Lilly, Forest, the Marriott Foundation, NIMH, Naurex, Orexigen, Pfizer, Shire, Takeda, and Transcept; and she is named as an inventor on U.S. Patent No. 6,323,236 B2 (Use of Sulfamate Derivatives for Treating Impulse Control Disorders), and along with the patent's assignee, the University of Cincinnati, she has received payments from Johnson & Johnson, the exclusive rightsholder. Dr. Grunze has received grants from the National Institute for Health Research, the Medical Research Council, the Northumberland, Tyne, and Wear National Health Service Foundation Trust, and Otsuka Pharmaceuticals; he has received honoraria for speaker bureaus or advisory panels from Bristol-Myers Squibb, Desitin, Gedeon-Richter, Hoffmann-LaRoche, and Lundbeck; and he has received honoraria for presenting at sponsored CME activities from Eli Lilly, Ferrer, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, and Servier. Dr. Altshuler was on an advisory board for Takeda and Lundbeck and attended an editorial board meeting sponsored by Sunovion; she received an honorarium as part of the 2014 Award for Research in Mood Disorders given by the American College of Psychiatrists; she performed a medical records review for the law offices of Hughes Socol Piers Resnick and Dym; and she was principal investigator and coinvestigator on research studies sponsored by NIMH. Dr. Keck is or has been a principal or coinvestigator on research studies sponsored by Alkermes, AstraZeneca, Cephalon, GlaxoSmithKline, Eli Lilly, the Marriott Foundation, NIMH, Orexigen, Pfizer, and Shire; he has been reimbursed for consulting to Alkermes, Bristol-Myers Squibb, Forest, Merck, Otsuka, ProPhase, Shire, Sunovion, Supernus, and Teva; he is listed as a coinventor on U.S. Patent No. 6,387,956 (Methods of Treating Obsessive-Compulsive Spectrum Disorders), and he has received no financial gain from this patent. Dr. Post has been a speaker for AstraZeneca, Sunovion, and Validus. Dr. Mintz, Dr. Hellemann, Dr. Nolen, Dr. Kupka, and Ms. Leverich report no financial relationships with commercial interests. NR 30 TC 1 Z9 1 U1 6 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD OCT PY 2016 VL 173 IS 10 BP 1015 EP 1023 DI 10.1176/appi.ajp.2016.15091119 PG 9 WC Psychiatry SC Psychiatry GA DX1WT UT WOS:000384158400013 PM 27079133 ER PT J AU Preston, KL Jobes, ML Phillips, KA Epstein, DH AF Preston, Kenzie L. Jobes, Michelle L. Phillips, Karran A. Epstein, David H. TI Real-time assessment of alcohol drinking and drug use in opioid-dependent polydrug users SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE alcohol; cocaine; craving; drug use; ecological momentary assessment; heroin; human ID ECOLOGICAL MOMENTARY ASSESSMENT; SELF-REPORT; COCAINE; HEROIN; INTERVENTION; CONSUMPTION; PREDICTORS; SYMPTOMS AB We investigated relationships between drinking, other drug use, and drug craving, using ecological momentary assessment (EMA), in a sample of polydrug users who were not heavy drinkers. In a prospective longitudinal cohort study, 114 heroin and cocaine users on methadone-maintenance treatment carried handheld electronic diaries during waking hours and were screened for drug and alcohol use for up to 25 weeks. Individuals who fulfilled the Diagnostic and Statistical Manual of Mental Disorders criteria for alcohol abuse or dependence were excluded. Participants responded to 2-5 random prompts per day to report on their moods, cravings, and activities and initiated entries when they used or acutely craved heroin or cocaine. Drinking alcohol was assessed in both types of entries. Breath alcohol was measured three times weekly. Participants reported drinking alcohol in 1.6% of random-prompt entries, 3.7% of event-contingent entries when craving cocaine and/or heroin, and 11.6% of eventcontingent entries when using cocaine and/or heroin. Alcohol drinking was also associated with higher craving ratings and prestudy alcohol use. More drinking was detected by ambulatory self-report than by in-clinic breath testing. Even though we had screened out heavy drinkers from our sample of polydrug users, drinking was associated with heroin and cocaine craving and actual use. Copyright (C) 2016 Wolters Kluwer Health, Inc. C1 [Preston, Kenzie L.; Jobes, Michelle L.; Phillips, Karran A.; Epstein, David H.] NIDA, Clin Pharmacol & Therapeut Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Preston, KL (reprint author), NIDA, Intramural Res Program, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM kpreston@intra.nida.nih.gov FU National Institute on Drug Abuse Intramural Research Program; Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health FX This work was supported by the National Institute on Drug Abuse Intramural Research Program.; This study was funded by the Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health. NR 31 TC 0 Z9 0 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0955-8810 EI 1473-5849 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD OCT PY 2016 VL 27 IS 7 BP 579 EP 584 DI 10.1097/FBP.0000000000000250 PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA DW1IW UT WOS:000383397700003 PM 27579810 ER PT J AU Madan, RA Karzai, FH Ning, YM Adesunloye, BA Huang, X Harold, N Couvillon, A Chun, G Cordes, L Sissung, T Beedie, SL Dawson, NA Theoret, MR McLeod, DG Rosner, I Trepel, JB Lee, MJ Tomita, Y Lee, S Chen, C Steinberg, SM Arlen, PM Gulley, JL Figg, WD Dahut, WL AF Madan, Ravi A. Karzai, Fatima H. Ning, Yang-Min Adesunloye, Bamidele A. Huang, Xuan Harold, Nancy Couvillon, Anna Chun, Guinevere Cordes, Lisa Sissung, Tristan Beedie, Shaunna L. Dawson, Nancy A. Theoret, Marc R. McLeod, David G. Rosner, Inger Trepel, Jane B. Lee, Min-Jung Tomita, Yusuke Lee, Sunmin Chen, Clara Steinberg, Seth M. Arlen, Philip M. Gulley, James L. Figg, William D. Dahut, William L. TI Phase II trial of docetaxel, bevacizumab, lenalidomide and prednisone in patients with metastatic castration-resistant prostate cancer SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; angiogenesis inhibition; combinationation therapy; metastatic castration resistant prostate cancer; docetaxel coimbination ID DOUBLE-BLIND; GENE POLYMORPHISMS; MULTIPLE-MYELOMA; TUMOR; CHEMOTHERAPY; THALIDOMIDE; EFFICACY; PLACEBO; GROWTH; MEN AB Objective To determine the safety and clinical efficacy of two anti-angiogenic agents, bevacizumab and lenalidomide, with docetaxel and prednisone. Patients and methods Eligible patients with metastatic castration-resistant prostate cancer enrolled in this open-label, phase II study of lenalidomide with bevacizumab (15 mg/kg), docetaxel (75 mg/m(2)) and prednisone (10 mg daily). Docetaxel and bevacizumab were administered on day 1 of a 3-week treatment cycle. To establish safety, lenalidomide dosing in this combination was escalated in a conventional 3 + 3 design (15, 20 and 25 mg daily for 2 weeks followed by 1 week off). Patients received supportive measures including prophylactic pegfilgrastim and enoxaparin. The primary endpoints were safety and clinical efficacy. Results A total of 63 patients enrolled in this trial. Toxicities were manageable with most common adverse events (AEs) being haematological, and were ascertained by weekly blood counts. Twenty-nine patients (46%) had grade 4 neutropenia, 20 (32%) had grade 3 anaemia and seven (11%) had grade 3 thrombocytopenia. Despite frequent neutropenia, serious infections were rare. Other common non-haematological grade 3 AEs included fatigue (10%) and diarrhoea (10%). Grade 2 AEs in > 10% of patients included anorexia, weight loss, constipation, osteonecrosis of the jaw, rash and dyspnoea. Of 61 evaluable patients, 57 (93%), 55 (90%) and 33 (54%) had PSA declines of > 30, > 50 and > 90%, respectively. Of the 29 evaluable patients, 24 (86%) had a confirmed radiographic partial response. The median times to progression and overall survival were 18.2 and 24.6 months, respectively. Conclusions With appropriate supportive measures, combination angiogenesis inhibition can be safely administered and potentially provide clinical benefit. These hypothesis-generating data would require randomized trials to confirm the findings. C1 [Madan, Ravi A.; Karzai, Fatima H.; Ning, Yang-Min; Adesunloye, Bamidele A.; Huang, Xuan; Harold, Nancy; Couvillon, Anna; Chun, Guinevere; Cordes, Lisa; Sissung, Tristan; Beedie, Shaunna L.; Theoret, Marc R.; Steinberg, Seth M.; Arlen, Philip M.; Gulley, James L.; Figg, William D.; Dahut, William L.] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Dawson, Nancy A.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [McLeod, David G.; Rosner, Inger] Walter Reed Natl Mil Med Ctr, Ctr Prostate Dis Res, Bethesda, MD USA. [Trepel, Jane B.; Lee, Min-Jung; Tomita, Yusuke; Lee, Sunmin] NCI, Dev Therapeut Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Chen, Clara] NCI, Radiol & Imaging Sci, Ctr Canc Res, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), Bldg 10 Rm 5A01,10 Ctr Dr, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov NR 30 TC 2 Z9 2 U1 5 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD OCT PY 2016 VL 118 IS 4 BP 590 EP 597 DI 10.1111/bju.13412 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA DW8HQ UT WOS:000383896300020 PM 26780387 ER PT J AU Liu, L Messer, K Baron, JA Lieberman, DA Jacobs, ET Cross, AJ Murphy, G Martinez, ME Gupta, S AF Liu, Lin Messer, Karen Baron, John A. Lieberman, David A. Jacobs, Elizabeth T. Cross, Amanda J. Murphy, Gwen Martinez, Maria Elena Gupta, Samir TI A prognostic model for advanced colorectal neoplasia recurrence SO CANCER CAUSES & CONTROL LA English DT Article DE Polyp surveillance; Risk stratification; Epidemiology; Colorectal cancer; Colorectal polyps ID GENERALIZED LINEAR-MODELS; SURVEILLANCE COLONOSCOPY; LOGISTIC-REGRESSION; RISK STRATIFICATION; ADENOMA RECURRENCE; COLON ADENOMAS; CANCER; PREDICTORS; POLYPECTOMY; TRIAL AB Following colonoscopic polypectomy, US Multisociety Task Force (USMSTF) guidelines stratify patients based on risk of subsequent advanced neoplasia (AN) using number, size, and histology of resected polyps, but have only moderate sensitivity and specificity. We hypothesized that a state-of-the-art statistical prediction model might improve identification of patients at high risk of future AN and address these challenges. Data were pooled from seven prospective studies which had follow-up ascertainment of metachronous AN within 3-5 years of baseline polypectomy (combined n = 8,228). Pooled data were randomly split into training (n = 5,483) and validation (n = 2,745) sets. A prognostic model was developed using best practices. Two risk cut-points were identified in the training data which achieved a 10 percentage point improvement in sensitivity and specificity, respectively, over current USMSTF guidelines. Clinical benefit of USMSTF versus model-based risk stratification was then estimated using validation data. The final model included polyp location, prior polyp history, patient age, and number, size and histology of resected polyps. The first risk cut-point improved sensitivity but with loss of specificity. The second risk cut-point improved specificity without loss of sensitivity (specificity 46.2 % model vs. 42.1 % guidelines, p < 0.001; sensitivity 75.8 % model vs. 74.0 % guidelines, p = 0.64). Estimated AUC was 65 % (95 % CI: 62-69 %). This model-based approach allows flexibility in trading sensitivity and specificity, which can optimize colonoscopy over- versus underuse rates. Only modest improvements in prognostic power are possible using currently available clinical data. Research considering additional factors such as adenoma detection rate for risk prediction appears warranted. C1 [Liu, Lin; Messer, Karen; Martinez, Maria Elena] Univ Calif San Diego, Dept Family Med & Publ Hlth, Div Biostat & Bioinformat, La Jolla, CA 92093 USA. [Liu, Lin; Messer, Karen; Martinez, Maria Elena; Gupta, Samir] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Baron, John A.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. [Lieberman, David A.] Vet Affairs Med Ctr, Div Gastroenterol & Hepatol, Portland, OR USA. [Lieberman, David A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Jacobs, Elizabeth T.] Univ Arizona, Ctr Canc, Arizona Coll Publ Hlth, Tucson, AZ USA. [Cross, Amanda J.] Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. [Cross, Amanda J.] Imperial Coll London, Dept Surg & Canc, Canc Screening & Prevent Res Grp, London, England. [Murphy, Gwen] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Rockville, MD USA. [Gupta, Samir] Vet Affairs San Diego Healthcare Syst, 3350 La Jolla Village Dr,MC 111D, San Diego, CA 92161 USA. [Gupta, Samir] Univ Calif San Diego, Dept Internal Med, Div Gastroenterol, La Jolla, CA 92093 USA. RP Gupta, S (reprint author), Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA.; Gupta, S (reprint author), Vet Affairs San Diego Healthcare Syst, 3350 La Jolla Village Dr,MC 111D, San Diego, CA 92161 USA.; Gupta, S (reprint author), Univ Calif San Diego, Dept Internal Med, Div Gastroenterol, La Jolla, CA 92093 USA. EM s1gupta@ucsd.edu FU Public Health Service Grants from the National Cancer Institute [CA-41108, CA-23074, CA95060, CA37287, CA104869, CA23108, CA59005, CA26852, 5R01CA155293]; Cooperative Studies Program, Department of Veterans Affairs; UCSD Department of Family Medicine and Public Health; United States Department of Veterans Affairs Health Services Research and Development Service of the VA Office of Research and Development [1 I01 HX001574-01A1] FX This work was supported in part by Public Health Service Grants, CA-41108, CA-23074, CA95060, CA37287, CA104869, CA23108, CA59005, CA26852, and 5R01CA155293 from the National Cancer Institute. Funding for the Veteran's Affairs Study was supported by the Cooperative Studies Program, Department of Veterans Affairs. The project described was also supported by a pilot grant from the UCSD Department of Family Medicine and Public Health (Liu, PI), as well as in part by Merit Review Award number 1 I01 HX001574-01A1 (Gupta, PI) from the United States Department of Veterans Affairs Health Services Research and Development Service of the VA Office of Research and Development. The views expressed in this article are those of the author(s) and do not necessarily represent the views of the Department of Veterans Affairs. NR 49 TC 0 Z9 0 U1 4 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD OCT PY 2016 VL 27 IS 10 BP 1175 EP 1185 DI 10.1007/s10552-016-0795-5 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA DW6MY UT WOS:000383766500001 PM 27517467 ER PT J AU Mazul, AL Siega-Riz, AM Weinberg, CR Engel, SM Zou, F Carrier, KS Basta, PV Vaksman, Z Maris, JM Diskin, SJ Maxen, C Naranjo, A Olshan, AF AF Mazul, Angela L. Siega-Riz, Anna Maria Weinberg, Clarice R. Engel, Stephanie M. Zou, Fei Carrier, Kathryn S. Basta, Patricia V. Vaksman, Zalman Maris, John M. Diskin, Sharon J. Maxen, Charlene Naranjo, Arlene Olshan, Andrew F. TI A family-based study of gene variants and maternal folate and choline in neuroblastoma: a report from the Children's Oncology Group SO CANCER CAUSES & CONTROL LA English DT Article DE Neuroblastoma; Genetics; Folate; Choline; Case-parent triad ID NEURAL-TUBE DEFECTS; GENOME-WIDE ASSOCIATION; CASE-PARENT TRIADS; ACUTE LYMPHOBLASTIC-LEUKEMIA; FOLIC-ACID; RISK; CANCER; POLYMORPHISMS; METAANALYSIS; SUSCEPTIBILITY AB Neuroblastoma is a childhood cancer of the sympathetic nervous system with embryonic origins. Previous epidemiologic studies suggest maternal vitamin supplementation during pregnancy reduces the risk of neuroblastoma. We hypothesized offspring and maternal genetic variants in folate-related and choline-related genes are associated with neuroblastoma and modify the effects of maternal intake of folate, choline, and folic acid. The Neuroblastoma Epidemiology in North America (NENA) study recruited 563 affected children and their parents through the Children's Oncology Group's Childhood Cancer Research Network. We used questionnaires to ascertain pre-pregnancy supplementation and estimate usual maternal dietary intake of folate, choline, and folic acid. We genotyped 955 genetic variants related to folate or choline using DNA extracted from saliva samples and used a log-linear model to estimate both child and maternal risk ratios and stratum-specific risk ratios for gene-environment interactions. Overall, no maternal or offspring genotypic results met criteria for a false discovery rate (FDR) Q-value < 0.2. Associations were also null for gene-environment interaction with pre-pregnancy vitamin supplementation, dietary folic acid, and folate. FDR-significant gene-choline interactions were found for offspring SNPs rs10489810 and rs9966612 located in MTHFD1L and TYMS, respectively, with maternal choline dietary intake dichotomized at the first quartile. These results suggest that variants related to one-carbon metabolism are not strongly associated with neuroblastoma. Choline-related variants may play a role; however, the functional consequences of the interacting variants are unknown and require independent replication. C1 [Mazul, Angela L.; Siega-Riz, Anna Maria; Engel, Stephanie M.; Carrier, Kathryn S.; Basta, Patricia V.; Olshan, Andrew F.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Campus Box 7435,2106 McGavran Greenberg Hall, Chapel Hill, NC 27599 USA. [Siega-Riz, Anna Maria] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Nutr, Chapel Hill, NC USA. [Weinberg, Clarice R.] NIEHS, Biostat & Computat Biol Branch, POB 12233, Res Triangle Pk, NC 27709 USA. [Zou, Fei] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Biostat, Chapel Hill, NC USA. [Basta, Patricia V.] Univ N Carolina, Biospecimen Proc Ctr, Chapel Hill, NC USA. [Vaksman, Zalman; Maris, John M.; Diskin, Sharon J.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Vaksman, Zalman; Maris, John M.; Diskin, Sharon J.] Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA. [Vaksman, Zalman] Childrens Hosp Philadelphia, Dept Biomed & Hlth Informat, Philadelphia, PA 19104 USA. [Maris, John M.; Diskin, Sharon J.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Maxen, Charlene] Akron Childrens Hosp, Showers Ctr Childhood Canc & Blood Disorder, Akron, OH USA. [Naranjo, Arlene] Univ Florida, Coll Med, Dept Biostat, Gainesville, FL USA. [Naranjo, Arlene] Univ Florida, Coll Publ Hlth & Hlth Profess, Dept Biostat, Gainesville, FL USA. RP Mazul, AL (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Campus Box 7435,2106 McGavran Greenberg Hall, Chapel Hill, NC 27599 USA. EM amazul@unc.edu FU National Cancer Institute [R01 CA 132887, R01 CA124709]; Lineberger Cancer Control Education Program [R25 CA57726] FX This research was supported in part by two grants from the National Cancer Institute (R01 CA 132887 and R01 CA124709) and the Lineberger Cancer Control Education Program (R25 CA57726). NR 47 TC 0 Z9 0 U1 6 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD OCT PY 2016 VL 27 IS 10 BP 1209 EP 1218 DI 10.1007/s10552-016-0799-1 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA DW6MY UT WOS:000383766500004 PM 27541142 ER PT J AU Dayan, E Thompson, RM Buch, ER Cohen, LG AF Dayan, Eran Thompson, Ryan M. Buch, Ethan R. Cohen, Leonardo G. TI 3D-printed head models for navigated non-invasive brain stimulation SO CLINICAL NEUROPHYSIOLOGY LA English DT Letter C1 [Dayan, Eran; Thompson, Ryan M.; Buch, Ethan R.; Cohen, Leonardo G.] NINDS, Human Cort Physiol & Neurorehabil Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. RP Dayan, E; Cohen, LG (reprint author), NINDS, Human Cort Physiol & Neurorehabil Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM eran_dayan@med.unc.edu; cohenl@ninds.nih.gov FU Intramural NIH HHS [Z99 NS999999] NR 6 TC 0 Z9 0 U1 5 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 EI 1872-8952 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD OCT PY 2016 VL 127 IS 10 BP 3341 EP 3342 DI 10.1016/j.clinph.2016.08.011 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DX0BU UT WOS:000384027300020 PM 27614003 ER PT J AU Shope, JT Zakrajsek, JS Finch, S Bingham, CR O'Neil, J Yano, S Wasserman, R Simons-Morton, B AF Shope, Jean T. Zakrajsek, Jennifer S. Finch, Stacia Bingham, C. Raymond O'Neil, Joseph Yano, Stephen Wasserman, Richard Simons-Morton, Bruce TI Translation to Primary Care of an Effective Teen Safe Driving Program for Parents SO CLINICAL PEDIATRICS LA English DT Article DE translation of evidence-based injury prevention; brief intervention study; teen driving; traffic accidents; Checkpoints(TM) program; adolescent risk taking; parents; primary care; Graduated Driver Licensing ID INJURY-PREVENTION; DRIVER EDUCATION; INTERVENTION; HEALTH; RISK; PEDIATRICS; ISSUES; LIMITS; CHILD AB Addressing teen driver crashes, this study adapted an effective Checkpoints(TM) program for parents of teen drivers for dissemination by primary care practitioners (PCPs) and the web; distributed the PCP/web program through pediatric practices; and examined dissemination to/implementation by parents. The website, youngDRIVERparenting.org, and brief intervention protocol were developed. PCPs delivered interventions and materials to parents, referred them to the website, and completed follow-up surveys. Google Analytics assessed parents' website use. Most PCPs reported delivering interventions with fidelity, and thought the program important and feasible. Brief interventions/website referrals, averaging 4.4 minutes, were delivered to 3465 (87%) of 3990 eligible parents by 133 PCPs over an 18-week average. Website visits (1453) were made by 42% of parents, who spent on average 3:53 minutes viewing 4.2 topics. This program costs little (its website, training and promotional materials are available) and could be one component of a comprehensive approach to reducing teen driver crashes. C1 [Shope, Jean T.; Zakrajsek, Jennifer S.; Bingham, C. Raymond] Univ Michigan, Transportat Res Inst, 2901 Baxter Rd, Ann Arbor, MI 48109 USA. [Finch, Stacia; Wasserman, Richard] Amer Acad Pediat, Elk Grove Village, IL USA. [O'Neil, Joseph] Riley Hosp Children, Indianapolis, IN USA. [Yano, Stephen] Childrens Med Associates Inc, Aiea, HI USA. [Wasserman, Richard] Univ Vermont, Coll Med, Burlington, VT USA. [Simons-Morton, Bruce] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Shope, JT (reprint author), Univ Michigan, Transportat Res Inst, 2901 Baxter Rd, Ann Arbor, MI 48109 USA. EM jshope@umich.edu OI Simons-Morton, Bruce/0000-0003-1099-6617 FU Centers for Disease Control and Prevention's National Center for Injury Prevention and Control [1R18CE001730]; HRSA MCHB [HRSA 5-UA6-10-001]; American Academy of Pediatrics (AAP); National Institutes of Health [UL1TR000005] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was funded by a grant (1R18CE001730) from the Centers for Disease Control and Prevention's National Center for Injury Prevention and Control. The Pediatric Research in Office Settings (PROS) Network receives core funding from the HRSA MCHB (HRSA 5-UA6-10-001) and the American Academy of Pediatrics (AAP). Pediatric PittNet is supported by the National Institutes of Health grant number UL1TR000005. NR 24 TC 0 Z9 0 U1 4 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0009-9228 EI 1938-2707 J9 CLIN PEDIATR JI Clin. Pediatr. PD OCT PY 2016 VL 55 IS 11 BP 1026 EP 1035 DI 10.1177/0009922816665086 PG 10 WC Pediatrics SC Pediatrics GA DW1EQ UT WOS:000383386200005 PM 27630004 ER PT J AU Cook, AJ Delong, E Murray, DM Vollmer, WM Heagerty, PJ AF Cook, Andrea J. Delong, Elizabeth Murray, David M. Vollmer, William M. Heagerty, Patrick J. TI Statistical lessons learned for designing cluster randomized pragmatic clinical trials from the NIH Health Care Systems Collaboratory Biostatistics and Design Core SO CLINICAL TRIALS LA English DT Article; Proceedings Paper CT 8th Annual Symposium on Statistical Issues in Clinical Trials CY APR, 2015 CL Univ Penn, Philadelphia, PA HO Univ Penn DE Pragmatic clinical trials; cluster-randomized; group randomized; electronic health record; NIH Collaboratory ID COVARIATE ADJUSTMENT; LONGITUDINAL DATA; BREAKING; OUTCOMES; MATCHES; MODELS; SIZE AB Background/aims: Pragmatic clinical trials embedded within health care systems provide an important opportunity to evaluate new interventions and treatments. Networks have recently been developed to support practical and efficient studies. Pragmatic trials will lead to improvements in how we deliver health care and promise to more rapidly translate research findings into practice. Methods: The National Institutes of Health (NIH) Health Care Systems Collaboratory was formed to conduct pragmatic clinical trials and to cultivate collaboration across research areas and disciplines to develop best practices for future studies. Through a two-stage grant process including a pilot phase (UH2) and a main trial phase (UH3), investigators across the Collaboratory had the opportunity to work together to improve all aspects of these trials before they were launched and to address new issues that arose during implementation. Seven Cores were created to address the various considerations, including Electronic Health Records; Phenotypes, Data Standards, and Data Quality; Biostatistics and Design Core; Patient-Reported Outcomes; Health Care Systems Interactions; Regulatory/Ethics; and Stakeholder Engagement. The goal of this article is to summarize the Biostatistics and Design Core's lessons learned during the initial pilot phase with seven pragmatic clinical trials conducted between 2012 and 2014. Results: Methodological issues arose from the five cluster-randomized trials, also called group-randomized trials, including consideration of crossover and stepped wedge designs. We outlined general themes and challenges and proposed solutions from the pilot phase including topics such as study design, unit of randomization, sample size, and statistical analysis. Our findings are applicable to other pragmatic clinical trials conducted within health care systems. Conclusion: Pragmatic clinical trials using the UH2/UH3 funding mechanism provide an opportunity to ensure that all relevant design issues have been fully considered in order to reliably and efficiently evaluate new interventions and treatments. The integrity and generalizability of trial results can only be ensured if rigorous designs and appropriate analysis choices are an essential part of their research protocols. C1 [Cook, Andrea J.] Grp Hlth Res Inst, Biostat Unit, 1730 Minor Ave Suite 1600, Seattle, WA 98101 USA. [Cook, Andrea J.; Heagerty, Patrick J.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Delong, Elizabeth] Duke Univ, Sch Med, Dept Biostat & Bioinformat, Durham, NC USA. [Delong, Elizabeth] Duke Clin Res Inst, Durham, NC USA. [Murray, David M.] NIH, Off Dis Prevent, Div Program Coordinat Planning & Strateg Initiat, Off Director, Bldg 10, Bethesda, MD 20892 USA. [Vollmer, William M.] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. RP Cook, AJ (reprint author), Grp Hlth Res Inst, Biostat Unit, 1730 Minor Ave Suite 1600, Seattle, WA 98101 USA. EM cook.aj@ghc.org FU NCCIH NIH HHS [UH2 AT007782, U54 AT007748, UH2 AT007755, UH2 AT007766, UH2 AT007769, UH2 AT007784, UH2 AT007788, UH2 AT007797]; NCI NIH HHS [UH3 CA188640] NR 38 TC 1 Z9 1 U1 8 U2 8 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 EI 1740-7753 J9 CLIN TRIALS JI Clin. Trials PD OCT PY 2016 VL 13 IS 5 BP 504 EP 512 DI 10.1177/1740774516646578 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DW1GZ UT WOS:000383392600006 PM 27179253 ER PT J AU Brittain, EH Proschan, MA AF Brittain, Erica H. Proschan, Michael A. TI Comments on Berry et al.'s response-adaptive randomization platform trial for Ebola SO CLINICAL TRIALS LA English DT Letter C1 [Brittain, Erica H.; Proschan, Michael A.] NIAID, Biostat Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Brittain, EH (reprint author), NIAID, Biostat Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ebrittain@niaid.nih.gov NR 4 TC 0 Z9 0 U1 1 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 EI 1740-7753 J9 CLIN TRIALS JI Clin. Trials PD OCT PY 2016 VL 13 IS 5 BP 566 EP 567 DI 10.1177/1740774516654440 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DW1GZ UT WOS:000383392600013 PM 27365017 ER PT J AU Berg, HE Ballard, ED Luckenbaugh, DA Nugent, AC Ionescu, DF Zarate, CA AF Berg, Hannah E. Ballard, Elizabeth D. Luckenbaugh, David A. Nugent, Allison C. Ionescu, Dawn F. Zarate, Carlos A., Jr. TI Recognition of emotional facial expressions in anxious and nonanxious depression SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID STAR-ASTERISK-D; MAJOR DEPRESSION; TRAIT ANXIETY; DISORDER; IDENTIFICATION; OUTPATIENTS; PERCEPTION; BIASES; MOOD AB Background: Anxiety and depression have each been independently associated with impairments in emotional face recognition. However, little is known about the nature of these impairments when anxiety and depression co-occur. Methods: This post-hoc analysis evaluated the relationship between anxiety status and performance on the Emotional Expression Multimorph Task within a clinical sample of individuals with major depressive disorder (MDD). Results: Participants with anxious depression (n = 14) and nonanxious depression (n = 14) completed the Emotional Expression Multimorph Task. Those with anxious depression required greater intensity of emotion to identify both happy (p = .01) and sad (p = .04) facial expressions than those with nonanxious depression. Severity of anxiety also correlated with greater intensity of emotion required to detect sad faces. Contrary to prediction, hypervigilance to angry and fearful facial expressions was not observed in anxious depression. Limitations: The present study did not include an anxiety-only group for comparison, and did not assess state anxiety at time of administration. In addition, the extent to which the experimental task correlates with social functioning is not fully understood. Conclusions: These findings suggest a diminished sensitivity to happy and sad facial expressions specific to anxious depression, but not a hypervigilance toward threatening facial expressions. Further research on the nature of emotion recognition in anxiety and depression may inform improved clinical interventions. Published by Elsevier Inc. C1 [Berg, Hannah E.; Ballard, Elizabeth D.; Luckenbaugh, David A.; Nugent, Allison C.; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Ionescu, Dawn F.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Ionescu, Dawn F.] Harvard Med Sch, Boston, MA USA. RP Ballard, ED (reprint author), Bldg 10,CRC Room 7-3345,10 Ctr Dr,MSC 1282, Bethesda, MD 20892 USA. EM Elizabeth.Ballard@nih.gov RI Ionescu, Dawn/K-5675-2015; OI Berg, Hannah/0000-0002-8283-0133 FU Intramural Research Program at the National Institute of Mental Health, National Institutes of Health IRP-NIMH-NIH; NCT [00,088,699]; ZIA [MH002927]; NARSAD; Brain and Behavior Mood Disorders Research Award FX Funding for this work was supported in part by the Intramural Research Program at the National Institute of Mental Health, National Institutes of Health IRP-NIMH-NIH; NCT#00,088,699; ZIA MH002927), by a NARSAD Independent Investigator to Dr. Zarate, and by a Brain and Behavior Mood Disorders Research Award to Dr. Zarate. These funding sources had no further role in study design; in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 27 TC 0 Z9 0 U1 11 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 0010-440X EI 1532-8384 J9 COMPR PSYCHIAT JI Compr. Psychiat. PD OCT PY 2016 VL 70 BP 1 EP 8 DI 10.1016/j.comppsych.2016.06.007 PG 8 WC Psychiatry SC Psychiatry GA DW8SJ UT WOS:000383925500001 PM 27624417 ER PT J AU Gmeiner, WH Gearhart, PJ Pommier, Y Nakamura, J AF Gmeiner, William H. Gearhart, Patricia J. Pommier, Yves Nakamura, Jun TI F10 cytotoxicity via topoisomerase I cleavage complex repair consistent with a unique mechanism for thymineless death SO FUTURE ONCOLOGY LA English DT Editorial Material DE DNA repair; DNA topoisomerase I; F10; thymineless death ID DNA-DAMAGE; CELL; INHIBITORS; SCREEN; RNA C1 [Gmeiner, William H.] Wake Forest Sch Med, Dept Canc Biol, Winston Salem, NC 27157 USA. [Gearhart, Patricia J.] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA. [Pommier, Yves] NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA. [Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Nakamura, Jun] Univ N Carolina, Chapel Hill, NC 27599 USA. RP Gmeiner, WH (reprint author), Wake Forest Sch Med, Dept Canc Biol, Winston Salem, NC 27157 USA. EM bgmeiner@wakehealth.edu FU NIEHS NIH HHS [P30 ES010126, P42 ES005948] NR 21 TC 1 Z9 1 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 EI 1744-8301 J9 FUTURE ONCOL JI Future Oncol. PD OCT PY 2016 VL 12 IS 19 BP 2183 EP 2188 DI 10.2217/fon-2016-0127 PG 6 WC Oncology SC Oncology GA DW2XG UT WOS:000383504900003 PM 27333295 ER PT J AU Zhang, LJ Bell, BA Li, Y Zhang, XM Fung, JJ Caspi, RR Lin, F AF Zhang, Lingjun Bell, Brent A. Li, Yan Zhang, Xiaomin Fung, John J. Caspi, Rachel R. Lin, Feng TI The lectin but not classical pathway of activation is important for complement to regulate the development of experimental autoimmune uveitis SO IMMUNOBIOLOGY LA English DT Meeting Abstract C1 [Zhang, Lingjun; Zhang, Xiaomin] Tianjin Med Univ, Inst Eye, Hosp Eye, Tianjin, Peoples R China. [Bell, Brent A.] Cleveland Clin, Cole Eye Inst, Cleveland, OH 44106 USA. [Li, Yan; Caspi, Rachel R.] NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. [Fung, John J.] Cleveland Clin, Inst Digest Dis, Cleveland, OH 44106 USA. [Zhang, Lingjun; Lin, Feng] Cleveland Clin, Dept Immunol, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0171-2985 J9 IMMUNOBIOLOGY JI Immunobiology PD OCT PY 2016 VL 221 IS 10 SI SI MA 6 BP 1133 EP 1133 DI 10.1016/j.imbio.2016.06.021 PG 1 WC Immunology SC Immunology GA DV3ER UT WOS:000382804300018 ER PT J AU Rus, V Nguyen, V Tatomir, A Boodhoo, D Mekala, AP Cudrici, C Badea, TC Rus, H AF Rus, Violeta Vinh Nguyen Tatomir, Alexandru Boodhoo, Dallas Mekala, Armugam P. Cudrici, Cornelia Badea, Tudor C. Rus, Horea TI RGC-32 promotes Th17 cell differentiation and enhances experimental autoimmune encephalomyelitis SO IMMUNOBIOLOGY LA English DT Meeting Abstract C1 [Rus, Violeta; Vinh Nguyen] Univ Maryland, Sch Med, Dept Med, Div Rheumatol & Clin Immunol, Baltimore, MD 21201 USA. [Tatomir, Alexandru; Boodhoo, Dallas; Mekala, Armugam P.] Sch Med, Dept Neurol, Baltimore, MD USA. [Cudrici, Cornelia; Badea, Tudor C.] NIH, Bethesda, MD 20892 USA. [Rus, Horea] Vet Adm Maryland Hlth Care Syst, Res Serv, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0171-2985 J9 IMMUNOBIOLOGY JI Immunobiology PD OCT PY 2016 VL 221 IS 10 SI SI MA 94 BP 1173 EP 1173 DI 10.1016/j.imbio.2016.06.109 PG 1 WC Immunology SC Immunology GA DV3ER UT WOS:000382804300106 ER PT J AU Ueda, Y Nishimura, J Sugimori, C Hosokawa, K Yonemura, Y Obara, N Noji, H Nakamura, Y Shirasugi, Y Ando, K Shichishima, T Ninomiya, H Chiba, S Kawaguchi, T Kanakura, Y Nakao, S AF Ueda, Yasutaka Nishimura, Jun-ichi Sugimori, Chiharu Hosokawa, Kohei Yonemura, Yuji Obara, Naoshi Noji, Hideyoshi Nakamura, Yoshihiko Shirasugi, Yukari Ando, Kiyoshi Shichishima, Tsutomu Ninomiya, Haruhiko Chiba, Shigeru Kawaguchi, Tatsuya Kanakura, Yuzuru Nakao, Shinji TI High sensitivity flow cytometry to detect small population of PNH clone in bone marrow failure syndrome in Japan SO IMMUNOBIOLOGY LA English DT Meeting Abstract C1 [Ueda, Yasutaka; Nishimura, Jun-ichi; Kanakura, Yuzuru] Osaka Univ, Grad Sch Med, Hematol & Oncol, Suita, Osaka, Japan. [Ueda, Yasutaka; Nishimura, Jun-ichi; Sugimori, Chiharu; Hosokawa, Kohei; Yonemura, Yuji; Obara, Naoshi; Noji, Hideyoshi; Nakamura, Yoshihiko; Shirasugi, Yukari; Ando, Kiyoshi; Shichishima, Tsutomu; Ninomiya, Haruhiko; Chiba, Shigeru; Kawaguchi, Tatsuya; Kanakura, Yuzuru; Nakao, Shinji] Japan PNH Study Grp, Tokyo, Japan. [Sugimori, Chiharu] Ishikawa Prefectural Cent Hosp, Hematol, Kanazawa, Ishikawa, Japan. [Hosokawa, Kohei] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Yonemura, Yuji] Kumamoto Univ Hosp, Transfus Med & Cell Therapy, Kumamoto, Japan. [Obara, Naoshi; Chiba, Shigeru] Univ Tsukuba, Hematol, Tsukuba, Ibaraki, Japan. [Noji, Hideyoshi] Fukushima Res Inst Environm & Med, Fukushima, Japan. [Nakamura, Yoshihiko; Shirasugi, Yukari; Ando, Kiyoshi] Tokai Univ, Sch Med, Hematol & Oncol, Isehara, Kanagawa, Japan. [Shichishima, Tsutomu] Fukushima Med Univ, Cardiol & Hematol, Fukushima, Japan. [Ninomiya, Haruhiko] Univ Tsukuba, Med Sci, Tsukuba, Ibaraki, Japan. [Kawaguchi, Tatsuya] Kumamoto Univ, Grad Sch Med Sci, Kumamoto, Japan. [Nakao, Shinji] Kanazawa Univ, Grad Sch Med Sci, Cellular Transplantat Biol, Kanazawa, Ishikawa, Japan. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0171-2985 J9 IMMUNOBIOLOGY JI Immunobiology PD OCT PY 2016 VL 221 IS 10 SI SI MA 122 BP 1186 EP 1186 DI 10.1016/j.imbio.2016.06.137 PG 1 WC Immunology SC Immunology GA DV3ER UT WOS:000382804300134 ER PT J AU Kolev, M Nova-Lamperti, E Freeley, S Smolarek, D Chakraborthy, S Mii, S Takahashi, M Smith, RA Afzali, B Kemper, C AF Kolev, Martin Nova-Lamperti, Estefania Freeley, Simon Smolarek, Dorota Chakraborthy, Shinjini Mii, Shinji Takahashi, Masahide Smith, Richard A. Afzali, Behdad Kemper, Claudia TI The C3-like molecule CD109 controls Th1 versus Th17 induction in CD4(+) T cells SO IMMUNOBIOLOGY LA English DT Meeting Abstract C1 [Kolev, Martin; Nova-Lamperti, Estefania; Freeley, Simon; Smolarek, Dorota; Chakraborthy, Shinjini; Smith, Richard A.; Afzali, Behdad; Kemper, Claudia] Kings Coll London, Guys Hosp Great Maze Pond, MRC Ctr Transplantat, Div Transplant Immunol & Mucosal Biol, London SE1 9RT, England. [Mii, Shinji; Takahashi, Masahide] Nagoya Univ, Grad Sch Med, Dept Pathol, Nagoya, Aichi, Japan. [Afzali, Behdad] NIAMSD, Mol Immunol & Inflammat Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0171-2985 J9 IMMUNOBIOLOGY JI Immunobiology PD OCT PY 2016 VL 221 IS 10 SI SI MA 142 BP 1195 EP 1196 DI 10.1016/j.imbio.2016.06.157 PG 2 WC Immunology SC Immunology GA DV3ER UT WOS:000382804300154 ER PT J AU Semba, RD Zhang, P Zhu, M Geng-Spyropoulos, M Shardell, M Gonzalez-Freire, M Eiriksdottir, G Gudnason, V Van Eyk, JE Ferrucci, L AF Semba, Richard D. Zhang, Pingbo Zhu, Min Geng-Spyropoulos, Minghui Shardell, Michelle Gonzalez-Freire, Marta Eiriksdottir, Gudny Gudnason, Vilmunder Van Eyk, Jennifer E. Ferrucci, Luigi TI A novel, multiplexed targeted mass spectrometry assay for quantification of complement factor H (CFH) variants and CFH-related proteins 1-5 in human plasma SO IMMUNOBIOLOGY LA English DT Meeting Abstract C1 [Semba, Richard D.; Zhang, Pingbo; Geng-Spyropoulos, Minghui] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. [Zhu, Min; Shardell, Michelle; Gonzalez-Freire, Marta; Ferrucci, Luigi] NIA, NIH, Baltimore, MD 21224 USA. [Eiriksdottir, Gudny; Gudnason, Vilmunder] Iceland Heart Assoc, Reykjavik, Iceland. [Eiriksdottir, Gudny; Gudnason, Vilmunder] Univ Iceland, Dept Med, Reykjavik, Iceland. [Van Eyk, Jennifer E.] Cedars Sinai Med Ctr, Adv Clin BioSyst Res Inst, Inst Heart, Los Angeles, CA 90048 USA. [Van Eyk, Jennifer E.] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0171-2985 J9 IMMUNOBIOLOGY JI Immunobiology PD OCT PY 2016 VL 221 IS 10 SI SI MA 155 BP 1201 EP 1201 DI 10.1016/j.imbio.2016.06.170 PG 1 WC Immunology SC Immunology GA DV3ER UT WOS:000382804300167 ER PT J AU Bigelow, RT Semenov, YR Anson, E du Lac, S Ferrucci, L Agrawal, Y AF Bigelow, Robin T. Semenov, Yevgeniy R. Anson, Eric du Lac, Sascha Ferrucci, Luigi Agrawal, Yuri TI Impaired Vestibular Function and Low Bone Mineral Density: Data from the Baltimore Longitudinal Study of Aging SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE vestibular; bone mineral density; aging; osteoporosis ID POSTMENOPAUSAL WOMEN; OLDER INDIVIDUALS; HEARING-LOSS; AGE; OSTEOPONTIN; BALANCE; LABYRINTHECTOMY AB Animal studies have demonstrated that experimentally induced vestibular ablation leads to a decrease in bone mineral density, through mechanisms mediated by the sympathetic nervous system. Loss of bone mineral density is a common and potentially morbid condition that occurs with aging, and we sought to investigate whether vestibular loss is associated with low bone mineral density in older adults. We evaluated this question in a cross-sectional analysis of data from the Baltimore Longitudinal Study of Aging (BLSA), a large, prospective cohort study managed by the National Institute on Aging (N = 389). Vestibular function was assessed with cervical vestibular evoked myogenic potentials (cVEMPs), a measure of saccular function. Bone mineral density was assessed using dual-energy X-ray absorptiometry (DEXA). In two-way t test analysis, we observed that individuals with reduced vestibular physiologic function had significantly lower bone mineral density. In adjusted multivariate linear regression analyses, we observed that older individuals with reduced vestibular physiologic function had significantly lower bone mineral density, specifically in weight-bearing hip and lower extremity bones. These results suggest that the vestibular system may contribute to bone homeostasis in older adults, notably of the weight-bearing hip bones at greatest risk of osteoporotic fracture. Further longitudinal analysis of vestibular function and bone mineral density in humans is needed to characterize this relationship and investigate the potential confounding effect of physical activity. C1 [Bigelow, Robin T.; Semenov, Yevgeniy R.; Anson, Eric; du Lac, Sascha; Agrawal, Yuri] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, 601 N Caroline St, Baltimore, MD 21287 USA. [du Lac, Sascha] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. RP Bigelow, RT (reprint author), Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, 601 N Caroline St, Baltimore, MD 21287 USA. EM rbigelow@jhmi.edu; ysemeno1@jhmi.edu; eanson1@jhmi.edu; sascha@jhmi.edu; ferruccilu@grc.nia.nih.gov; yagrawa1@jhmi.edu FU National Institutes of Health [NIH/NIDCD K23 DC013056, 5T32 DC000023-30]; National Institute on Aging FX This work was supported by the National Institutes of Health grant NIH/NIDCD K23 DC013056 and 5T32 DC000023-30. The Baltimore Longitudinal Study of Aging is supported by the National Institute on Aging. NR 38 TC 0 Z9 0 U1 6 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 EI 1438-7573 J9 JARO-J ASSOC RES OTO JI JARO PD OCT PY 2016 VL 17 IS 5 BP 433 EP 440 DI 10.1007/s10162-016-0577-5 PG 8 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA DW3BX UT WOS:000383518200004 PM 27447468 ER PT J AU Sigurdardottir, LG Markt, SC Sigurdsson, S Aspelund, T Fall, K Schernhammer, E Rider, JR Launer, L Harris, T Stampfer, MJ Gudnason, V Czeisler, CA Lockley, SW Valdimarsdottir, UA Mucci, LA AF Sigurdardottir, Lara G. Markt, Sarah C. Sigurdsson, Sigurdur Aspelund, Thor Fall, Katja Schernhammer, Eva Rider, Jennifer R. Launer, Lenore Harris, Tamara Stampfer, Meir J. Gudnason, Vilmundur Czeisler, Charles A. Lockley, Steven W. Valdimarsdottir, Unnur A. Mucci, Lorelei A. TI Pineal Gland Volume Assessed by MRI and Its Correlation with 6-Sulfatoxymelatonin Levels among Older Men SO JOURNAL OF BIOLOGICAL RHYTHMS LA English DT Article DE pineal; melatonin; sleep; circadian; MRI ID PLASMA MELATONIN; SLEEP DISRUPTION; PRIMARY INSOMNIA; PROSTATE-CANCER; HUMANS; SUPPRESSION; SECRETION; AGE; CALCIFICATION; EXCRETION AB The pineal gland produces the hormone melatonin, and its volume may influence melatonin levels. We describe an innovative method for estimating pineal volume in humans and present the association of pineal parenchyma volume with levels of the primary melatonin metabolite, 6-sulfatoxymelatonin. We selected a random sample of 122 older Icelandic men nested within the AGES-Reykjavik cohort and measured their total pineal volume, their parenchyma volume, and the extent of calcification and cysts. For volume estimations we used manual segmentation of magnetic resonance images in the axial plane with simultaneous side-by-side view of the sagittal and coronal plane. We used multivariable adjusted linear regression models to estimate the association of pineal parenchyma volume and baseline characteristics, including 6-sulfatoxymelatonin levels. We used logistic regression to test for differences in first morning urinary 6-sulfatoxymelatonin levels among men with or without cystic or calcified glands. The pineal glands varied in volume, shape, and composition. Cysts were present in 59% of the glands and calcifications in 21%. The mean total pineal volume measured 207 mm(3) (range 65-536 mm(3)) and parenchyma volume 178 mm(3) (range 65-503 mm(3)). In multivariable-adjusted models, pineal parenchyma volume was positively correlated with 6-sulfatoxymelatonin levels ( = 0.52, p < 0.001). Levels of 6-sulfatoxymelatonin did not differ significantly by presence of cysts or calcification. By using an innovative method for pineal assessment, we found pineal parenchyma volume to be positively correlated with 6-sulfatoxymelatonin levels, in line with other recent studies. C1 [Sigurdardottir, Lara G.] Iceland Canc Soc, IS-108 Reykjavik, Iceland. [Sigurdardottir, Lara G.; Aspelund, Thor; Valdimarsdottir, Unnur A.; Mucci, Lorelei A.] Univ Iceland, Ctr Publ Hlth Sci, Reykjavik, Iceland. [Sigurdardottir, Lara G.; Gudnason, Vilmundur; Valdimarsdottir, Unnur A.] Univ Iceland, Fac Med, Reykjavik, Iceland. [Markt, Sarah C.; Schernhammer, Eva; Rider, Jennifer R.; Stampfer, Meir J.; Valdimarsdottir, Unnur A.; Mucci, Lorelei A.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Sigurdsson, Sigurdur; Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Fall, Katja] Univ Orebro, Sch Med Sci, Clin Epidemiol & Biostat, Orebro, Sweden. [Schernhammer, Eva; Stampfer, Meir J.; Mucci, Lorelei A.] Harvard Med Sch, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA USA. [Schernhammer, Eva] Med Univ Vienna, Dept Epidemiol, Vienna, Austria. [Launer, Lenore; Harris, Tamara] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, Bethesda, MD 20892 USA. [Czeisler, Charles A.; Lockley, Steven W.] Brigham & Womens Hosp, Dept Med, Div Sleep & Circadian Disorders, 75 Francis St, Boston, MA 02115 USA. [Czeisler, Charles A.; Lockley, Steven W.] Harvard Med Sch, Div Sleep Med, Boston, MA USA. RP Sigurdardottir, LG (reprint author), Iceland Canc Soc, IS-108 Reykjavik, Iceland. EM lara@sessionimpossible.com OI Fall, Katja/0000-0002-3649-2639 FU RANNIS (the Icelandic Research Fund); National Institutes on Aging Intramural Research Program [N01-AG-12100]; Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament); Harvard Catalyst Award; National Cancer Institute at the National Institutes of Health Training Grant [NIH T32 CA09001]; Prostate Cancer Foundation FX This study was supported by RANNIS (the Icelandic Research Fund). The AGES-Reykjavik is supported by Contract N01-AG-12100 from the National Institutes on Aging Intramural Research Program; Hjartavernd (the Icelandic Heart Association); the Althingi (the Icelandic Parliament); and the Harvard Catalyst Award. This study is approved by the Icelandic National Bioethics Committee, VSN: 00-063. S.C.M. is supported by the National Cancer Institute at the National Institutes of Health Training Grant NIH T32 CA09001. L.A.M. and J.R.R. are supported by the Prostate Cancer Foundation. The funding agencies had no role in the design of the study, the collection of the data, or the data analysis. NR 40 TC 1 Z9 1 U1 4 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0748-7304 EI 1552-4531 J9 J BIOL RHYTHM JI J. Biol. Rhythms PD OCT PY 2016 VL 31 IS 5 BP 461 EP 469 DI 10.1177/0748730416656948 PG 9 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA DW1XK UT WOS:000383436700004 PM 27449477 ER PT J AU Canepa, M Bezante, G Vianello, P Ameri, P Milaneschi, Y Aste, M Cavalla, F Bauckneht, M Marini, C Balbi, M Brunelli, C Sambuceti, G AF Canepa, Marco Bezante, Gianpaolo Vianello, Pierfilippo Ameri, Pietro Milaneschi, Yuri Aste, Milena Cavalla, Francesca Bauckneht, Matteo Marini, Cecilia Balbi, Manrico Brunelli, Claudio Sambuceti, Gianmario TI Diagnostic value of ischemia severity at myocardial perfusion imaging in elderly persons with suspected coronary disease SO JOURNAL OF CARDIOVASCULAR MEDICINE LA English DT Article DE coronary artery disease; diagnostic accuracy; ischemia; myocardial perfusion scintigraphy; summed score ID EMISSION COMPUTED-TOMOGRAPHY; ARTERY-DISEASE; CARDIAC DEATH; RISK STRATIFICATION; PROGNOSTIC VALUE; MEDICAL THERAPY; GUIDELINES; PREDICTION; EXERCISE; IMPACT AB AimsMyocardial perfusion and ischemia scores obtained from myocardial perfusion scintigraphy (MPS) have strong independent prognostic value in elderly individuals without known coronary artery disease (CAD). Herein we aimed to assess their independent diagnostic value and accuracy for CAD while considering different thresholds of myocardial ischemia.MethodsWe estimated the summed rest score (SRS), summed stress score (SSS) and summed difference score (SDS) in 322 elderly individuals (mean age 727 years, 68% men) who underwent coronary angiography following an MPS. Abnormal perfusion at stress was defined as an SSS greater than 3, and ischemia as an SDS of at least 2, and further categorized as mild (2-4), moderate (5-7) or severe (>7). Multivariate logistic regressions were used to establish the independent diagnostic value and accuracy of MPS parameters.ResultsCAD was diagnosed in 182 individuals (56%). In multivariate analysis accounting for clinical variables associated with CAD including the Framingham risk score, both SRS [odds ratio (OR) 1.09, 95% confidence interval (CI) 1.01-1.18, P=0.03] and SSS (OR 1.10, 95% CI 1.04-1.16, P=0.0006) and SDS (OR 1.12, 95% CI 1.04-1.21, P=0.003) were independently associated with CAD. An SSS greater than 3 was also independently associated with CAD (OR 2.51, 95% CI 1.43-4.39, P=0.0013), whereas an SDS of 2 or greater was not (OR 1.62, 95% CI 0.89-2.93, P=0.12), but only when at least 5 (OR 2.31, 95% CI 1.32-4.03, P=0.003). The probability of CAD was proportional to the amount of myocardial ischemia in those with an SSS greater than 3, and lower and comparable in those with an SSS of at least 3 or an SSS greater than 3 with SDS of 1 or less (P=0.19). Increasing the threshold of myocardial ischemia determined a decrease in sensitivity and increase in specificity of MPS for both diagnosis and severity of CAD.ConclusionWe established the diagnostic value and accuracy of continuous scores and thresholds of abnormal myocardial perfusion and ischemia previously validated in prognostic studies. Their more widespread use could potentially improve the diagnostic yield of coronary angiography in elderly individuals with suspected CAD. C1 [Canepa, Marco; Bezante, Gianpaolo; Vianello, Pierfilippo; Ameri, Pietro; Aste, Milena; Cavalla, Francesca; Balbi, Manrico; Brunelli, Claudio] Univ Genoa, Dept Internal Med, Cardiovasc Unit, Genoa, Italy. [Canepa, Marco] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA. [Milaneschi, Yuri] Vrije Univ Amsterdam, Med Ctr GGZ Geest, Dept Psychiat, Amsterdam, Netherlands. [Bauckneht, Matteo; Marini, Cecilia; Sambuceti, Gianmario] Univ Genoa, Dept Hlth Sci, Nucl Med, Genoa, Italy. RP Canepa, M (reprint author), Univ Genoa, Cardiovasc Unit, Dept Internal Med, IRCCS AOU San Martino IST, Viale Benedetto 15,6, I-16132 Genoa, Italy. EM marco.canepa@unige.it OI Bauckneht, Matteo/0000-0002-1937-9116 NR 28 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 1558-2027 EI 1558-2035 J9 J CARDIOVASC MED JI J. Cardiovasc. Med. PD OCT PY 2016 VL 17 IS 10 BP 719 EP 728 DI 10.2459/JCM.0000000000000339 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DW9DE UT WOS:000383954800002 PM 26599683 ER PT J AU Rozins, C Day, T AF Rozins, Carly Day, Troy TI Disease eradication on large industrial farms SO JOURNAL OF MATHEMATICAL BIOLOGY LA English DT Article DE Impulsive differential equation; Poultry; SIR; Infectious disease; Livestock production; All-in-all-out; Indirect transmission ID MAREKS-DISEASE; UNITED-STATES; SEA LICE; TRANSMISSION; WELFARE; VIRUS AB Many modern farms exhibit all-in-all-out dynamics in which entire cohorts of livestock are removed from a farm before a new cohort is introduced. This industrialization has enabled diseases to spread rapidly within farms. Here we look at one such example, Marek's disease. Marek's disease is an economically important disease of poultry. The disease is transmitted indirectly, enabling the spread of disease between cohorts of chickens who have never come into physical contact. We develop a model which allows us to track the transmission of disease within a barn and between subsequent cohorts of chickens occupying the barn. It is described by a system of impulsive differential equations. We determine the conditions that lead to disease eradication. For a given level of transmission we find that disease eradication is possible if the cohort length is short enough and/or the cohort size is small enough. Marek's disease can also be eradicated from a farm if the cleaning effort between cohorts is large enough. Importantly complete cleaning is not required for eradication and the threshold cleaning effort needed declines as both cohort duration and size decrease. C1 [Rozins, Carly; Day, Troy] Queens Univ, Dept Math & Stat, Kingston, ON, Canada. [Day, Troy] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. RP Rozins, C (reprint author), Queens Univ, Dept Math & Stat, Kingston, ON, Canada. EM crozins@mast.queensu.ca NR 20 TC 1 Z9 1 U1 7 U2 7 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0303-6812 EI 1432-1416 J9 J MATH BIOL JI J. Math. Biol. PD OCT PY 2016 VL 73 IS 4 BP 885 EP 902 DI 10.1007/s00285-016-0973-9 PG 18 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA DV5AH UT WOS:000382937000005 PM 26898368 ER PT J AU Kraemmer, J Smith, K Weintraub, D Guillemot, V Nalls, MA Cormier-Dequaire, F Moszer, I Brice, A Singleton, AB Corvol, JC AF Kraemmer, Julia Smith, Kara Weintraub, Daniel Guillemot, Vincent Nalls, Mike A. Cormier-Dequaire, Florence Moszer, Ivan Brice, Alexis Singleton, Andrew B. Corvol, Jean-Christophe TI Clinical-genetic model predicts incident impulse control disorders in Parkinson's disease SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID DNA-SEQUENCING DATA; ASSOCIATION; RECEPTOR; POLYMORPHISMS; BEHAVIORS; SUSCEPTIBILITY; ADDICTIONS; FRAMEWORK; SYMPTOMS; GRIN2B AB Objectives Impulse control disorders (ICD) are commonly associated with dopamine replacement therapy (DRT) in patients with Parkinson's disease (PD). Our aims were to estimate ICD heritability and to predict ICD by a candidate genetic multivariable panel in patients with PD. Methods Data from de novo patients with PD, drug-naive and free of ICD behaviour at baseline, were obtained from the Parkinson's Progression Markers Initiative cohort. Incident ICD behaviour was defined as positive score on the Questionnaire for Impulsive-Compulsive Disorders in PD. ICD heritability was estimated by restricted maximum likelihood analysis on whole exome sequencing data. 13 candidate variants were selected from the DRD2, DRD3, DAT1, COMT, DDC, GRIN2B, ADRA2C, SERT, TPH2, HTR2A, OPRK1 and OPRM1 genes. ICD prediction was evaluated by the area under the curve (AUC) of receiver operating characteristic (ROC) curves. Results Among 276 patients with PD included in the analysis, 86% started DRT, 40% were on dopamine agonists (DA), 19% reported incident ICD behaviour during follow-up. We found heritability of this symptom to be 57%. Adding genotypes from the 13 candidate variants significantly increased ICD predictability (AUC=76%, 95% CI (70% to 83%)) compared to prediction based on clinical variables only (AUC=65%, 95% CI (58% to 73%), p=0.002). The clinical-genetic prediction model reached highest accuracy in patients initiating DA therapy (AUC=87%, 95% CI (80% to 93%)). OPRK1, HTR2A and DDC genotypes were the strongest genetic predictive factors. Conclusions Our results show that adding a candidate genetic panel increases ICD predictability, suggesting potential for developing clinical-genetic models to identify patients with PD at increased risk of ICD development and guide DRT management. C1 [Kraemmer, Julia; Guillemot, Vincent; Cormier-Dequaire, Florence; Moszer, Ivan; Brice, Alexis; Corvol, Jean-Christophe] Univ Paris 06, Sorbonne Univ, Paris, France. [Kraemmer, Julia; Guillemot, Vincent; Cormier-Dequaire, Florence; Moszer, Ivan; Brice, Alexis; Corvol, Jean-Christophe] INSERM, UMRS 1127, Paris, France. [Kraemmer, Julia; Guillemot, Vincent; Cormier-Dequaire, Florence; Moszer, Ivan; Brice, Alexis; Corvol, Jean-Christophe] CIC 1422, Paris, France. [Kraemmer, Julia; Guillemot, Vincent; Cormier-Dequaire, Florence; Moszer, Ivan; Brice, Alexis; Corvol, Jean-Christophe] CNRS, UMR 7225, Paris, France. [Kraemmer, Julia; Guillemot, Vincent; Cormier-Dequaire, Florence; Moszer, Ivan; Brice, Alexis; Corvol, Jean-Christophe] AP HP, Paris, France. [Kraemmer, Julia; Guillemot, Vincent; Cormier-Dequaire, Florence; Moszer, Ivan; Brice, Alexis; Corvol, Jean-Christophe] ICM, Dept Malad Syst Nerveux, Paris, France. [Kraemmer, Julia; Guillemot, Vincent; Cormier-Dequaire, Florence; Moszer, Ivan; Brice, Alexis; Corvol, Jean-Christophe] Hop La Pitie Salpetriere, Dept Genet, Paris, France. [Kraemmer, Julia] Med Univ Vienna, Vienna, Austria. [Smith, Kara; Weintraub, Daniel] Univ Penn, Perelman Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Corporal Michael J Crescenz Dept Vet Affairs Med, Philadelphia, PA USA. [Nalls, Mike A.; Singleton, Andrew B.] NIH, Lab Neurogenet, Bldg 10, Bethesda, MD 20892 USA. RP Corvol, JC (reprint author), Hop La Pitie Salpetriere, ICM, CIC Neurosci, 47-83 Bd Hop, F-75013 Paris, France. EM jean-christophe.corvol@aphp.fr RI corvol, jean-christophe/I-6387-2012 OI corvol, jean-christophe/0000-0001-7325-0199 FU Michael J Fox Foundation for Parkinson's Research; AbbVie; Avid Radiopharmaceuticals; Biogen; Bristol-Myers Squibb; Covance; GE Healthcare; Genentech; GlaxoSmithKline; Lilly; Lundbeck; Merck; Meso Scale Discovery; Pfizer; Piramal; Roche; Servier; UCB; programme 'Investissements d'Avenir' [ANR-10-IAIHU-06]; Medtronic Inc. FX PPMI-a public-private partnership-is funded by the Michael J Fox Foundation for Parkinson's Research and funding partners, including AbbVie, Avid Radiopharmaceuticals, Biogen, Bristol-Myers Squibb, Covance, GE Healthcare, Genentech, GlaxoSmithKline, Lilly, Lundbeck, Merck, Meso Scale Discovery, Pfizer, Piramal, Roche, Servier and UCB. J-CC, IM and VG were supported by a funding from the programme 'Investissements d'Avenir' ANR-10-IAIHU-06; and KS by Medtronic Inc. NR 41 TC 7 Z9 7 U1 11 U2 11 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 EI 1468-330X J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD OCT PY 2016 VL 87 IS 10 BP 1106 EP 1111 DI 10.1136/jnnp-2015-312848 PG 6 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA DW9OU UT WOS:000383991400011 PM 27076492 ER PT J AU Lopker, MJ Del Prete, GQ Estes, JD Li, H Reid, C Newman, L Lipkey, L Camus, C Easlick, JL Wang, SY Decker, JM Bar, KJ Learn, G Pal, R Weiss, DE Hahn, BH Lifson, JD Shaw, GM Keele, BF AF Lopker, Michael J. Del Prete, Gregory Q. Estes, Jacob D. Li, Hui Reid, Carolyn Newman, Laura Lipkey, Leslie Camus, Celine Easlick, Juliet L. Wang, Shuyi Decker, Julie M. Bar, Katharine J. Learn, Gerald Pal, Ranajit Weiss, Deborah E. Hahn, Beatrice H. Lifson, Jeffrey D. Shaw, George M. Keele, Brandon F. TI Derivation and Characterization of Pathogenic Transmitted/Founder Molecular Clones from Simian Immunodeficiency Virus SIVsmE660 and SIVmac251 following Mucosal Infection SO JOURNAL OF VIROLOGY LA English DT Article ID RHESUS MACAQUES; ENVELOPE PROTEIN; SUBOPTIMAL NUCLEOTIDES; INTRARECTAL CHALLENGE; MONOCLONAL-ANTIBODIES; BIOLOGICAL PHENOTYPE; REPLICATIVE FITNESS; VACCINE CHALLENGE; GENETIC IDENTITY; NONHUMAN PRIMATE AB Currently available simian immunodeficiency virus (SIV) infectious molecular clones (IMCs) and isolates used in nonhuman primate (NHP) models of AIDS were originally derived from infected macaques during chronic infection or end stage disease and may not authentically recapitulate features of transmitted/founder (T/F) genomes that are of particular interest in transmission, pathogenesis, prevention, and treatment studies. We therefore generated and characterized T/F IMCs from genetically and biologically heterogeneous challenge stocks of SIVmac251 and SIVsmE660. Single-genome amplification (SGA) was used to identify full-length T/F genomes present in plasma during acute infection resulting from atraumatic rectal inoculation of Indian rhesus macaques with low doses of SIVmac251 or SIVsmE660. All 8 T/F clones yielded viruses that were infectious and replication competent in vitro, with replication kinetics similar to those of the widely used chronic-infection-derived IMCs SIVmac239 and SIVsmE543. Phenotypically, the new T/F virus strains exhibited a range of neutralization sensitivity profiles. Four T/F virus strains were inoculated into rhesus macaques, and each exhibited typical SIV replication kinetics. The SIVsm T/F viruses were sensitive to TRIM5 alpha restriction. All T/F viruses were pathogenic in rhesus macaques, resulting in progressive CD4(+) T cell loss in gastrointestinal tissues, peripheral blood, and lymphatic tissues. The animals developed pathological immune activation; lymphoid tissue damage, including fibrosis; and clinically significant immunodeficiency leading to AIDS-defining clinical endpoints. These T/F clones represent a new molecular platform for the analysis of virus transmission and immunopathogenesis and for the generation of novel "bar-coded" challenge viruses and next-generation simian-human immunodeficiency viruses that may advance the HIV/AIDS vaccine agenda. IMPORTANCE Nonhuman primate research has relied on only a few infectious molecular clones for a myriad of diverse research projects, including pathogenesis, preclinical vaccine evaluations, transmission, and host-versus-pathogen interactions. With new data suggesting a selected phenotype of the virus that causes infection (i.e., the transmitted/founder virus), we sought to generate and characterize infectious molecular clones from two widely used simian immunodeficiency virus lineages (SIVmac251 and SIVsmE660). Although the exact requirements necessary to be a T/F virus are not yet fully understood, we generated cloned viruses with all the necessary characteristic of a successful T/F virus. The cloned viruses revealed typical acute and set point viral-load dynamics with pathological immune activation, lymphoid tissue damage progressing to significant immunodeficiency, and AIDS-defining clinical endpoints in some animals. These T/F clones represent a new molecular platform for studies requiring authentic T/F viruses. C1 [Lopker, Michael J.; Easlick, Juliet L.; Decker, Julie M.] Univ Alabama Birmingham, Birmingham, AL USA. [Del Prete, Gregory Q.; Estes, Jacob D.; Reid, Carolyn; Newman, Laura; Lipkey, Leslie; Camus, Celine; Lifson, Jeffrey D.; Keele, Brandon F.] Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD USA. [Li, Hui; Wang, Shuyi; Bar, Katharine J.; Learn, Gerald; Hahn, Beatrice H.; Shaw, George M.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Pal, Ranajit] Adv BioSci Labs Inc, Rockville, MD USA. [Weiss, Deborah E.] Bioqual, Rockville, MD USA. RP Keele, BF (reprint author), Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD USA. EM keelebf@mail.nih.gov FU HHS | NIH | National Cancer Institute (NCI) [HHSN261200800001E]; HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) [AI087383]; NIAID [AI087383]; National Cancer Institute; National Institutes of Health [HHSN261200800001E] FX This work, including the efforts of Gregory Q. Del Prete, Jacob D. Estes, Carolyn Reid, Laura Newman, Leslie Lipkey, Celine Camus, Jeffrey Lifson, and Brandon F. Keele, was funded by HHS | NIH | National Cancer Institute (NCI) (HHSN261200800001E). This work, including the efforts of Michael Lopker, Beatrice H. Hahn, and George M. Shaw, was funded by HHS| NIH | National Institute of Allergy and Infectious Diseases (NIAID) (AI087383).; This work was supported in part with federal funds from NIAID grant AI087383 and the National Cancer Institute; National Institutes of Health under contract 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 63 TC 2 Z9 2 U1 5 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD OCT PY 2016 VL 90 IS 19 BP 8435 EP 8453 DI 10.1128/JVI.00718-16 PG 19 WC Virology SC Virology GA DW6LH UT WOS:000383761900006 PM 27412591 ER PT J AU Gach, JS Venzon, D Vaccari, M Keele, BF Franchini, G Forthal, DN AF Gach, Johannes S. Venzon, David Vaccari, Monica Keele, Brandon F. Franchini, Genoveffa Forthal, Donald N. TI Relationship between Vaccine-Induced Antibody Capture of Infectious Virus and Infection Outcomes following Repeated Low-Dose Rectal Challenges with Simian Immunodeficiency Virus SIVmac251 SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 INFECTION; DEPENDENT ENHANCEMENT; MEDIATED ENHANCEMENT; TYPE-1; TRIAL; PROTECTION; GP120; CD4; FC; ACQUISITION AB Antibodies are known to enhance in vitro infection by human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). We measured the ability of antibodies induced by ALVAC-SIV/gp120 vaccination, given with alum or MF59 adjuvant, to capture infectious SIVmac251 and determined the association between capture and infection outcomes following low-dose, repeated rectal challenge of rhesus macaques. We found that capture correlated with the number of transmitted/founder (T/F) variants that established infection, such that animals whose plasma captured more virus were infected with a higher number of T/F strains. Capture also correlated with results of Env binding assays, indicating that greater immunogenicity resulted in greater capture. Although vaccination elicited negligible neutralizing activity against the challenge strain (50% inhibitory dilutions of >1/80 in all cases), animals with low capture and whose plasma, at a fixed dilution, inhibited a higher fraction of virus were infected at a lower rate than animals with high capture and low neutralization (P = 0.039); only animals with the low capture/high neutralization response profile were protected compared with unvaccinated control animals (P = 0.026). In a sieve analysis, high capture and low capture were distinguishable on the basis of polymorphisms in the V1 loop of Env at amino acids 144 and 145. Our results indicate that vaccine-induced antibody that binds to and captures infectious virus but does not inhibit its infectivity may enhance the likelihood of infection following rectal challenge with SIVmac251. Higher immunogenicity resulting in better antibody capture but similar anti-infectivity may not improve vaccine efficacy. IMPORTANCE Vaccines generally prevent viral infections by eliciting antibodies that inhibit virus infectivity. However, antibodies, including those induced by vaccination, have the potential to enhance, rather than prevent infection. We measured the ability of vaccine-induced antibodies to capture infectious simian immunodeficiency virus (SIV) and explored the relationship between virus capture and infection outcomes. We found that capture correlated with the number of SIV variants that established infection, such that animals whose plasma captured more virus were infected with a higher number of unique strains. In addition, animals whose sera had high capture but weak anti-infectivity activity were infected at a higher rate than were animals with low capture and stronger anti-infectivity activity. These results suggest that vaccines that induce antibodies that bind to and capture infectious virus but do not inhibit virus infectivity will not be effective in preventing infection. C1 [Gach, Johannes S.; Forthal, Donald N.] Univ Calif Irvine, Dept Med, Div Infect Dis, Irvine, CA 92717 USA. [Gach, Johannes S.; Forthal, Donald N.] Univ Calif Irvine, Dept Mol Biol & Biochem, Div Infect Dis, Irvine, CA 92717 USA. [Venzon, David] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. [Vaccari, Monica; Franchini, Genoveffa] NCI, Anim Models & Vaccine Sect, Bethesda, MD 20892 USA. [Keele, Brandon F.] Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick Natl Lab, Frederick, MD USA. RP Forthal, DN (reprint author), Univ Calif Irvine, Dept Med, Div Infect Dis, Irvine, CA 92717 USA.; Forthal, DN (reprint author), Univ Calif Irvine, Dept Mol Biol & Biochem, Div Infect Dis, Irvine, CA 92717 USA. EM dnfortha@uci.edu OI Gach, Johannes/0000-0002-5043-5710 FU HHS | NIH | National Cancer Institute (NCI) [HHSN261200800001E]; HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) [R01AI102715, R01AI118581]; National Institute of Allergy and Infectious Diseases of the National Institutes of Health [R01AI102715, R01AI118581]; National Cancer Institute [HHSN261200800001E] FX This work, including the efforts of Brandon F. Keele, was funded by HHS | NIH | National Cancer Institute (NCI) (HHSN261200800001E). This work, including the efforts of Donald N. Forthal, was funded by HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) (R01AI102715 and R01AI118581).; 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 R01AI102715 and R01AI118581 and in part by federal funds from the National Cancer Institute under contract HHSN261200800001E. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 22 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD OCT PY 2016 VL 90 IS 19 BP 8487 EP 8495 DI 10.1128/JVI.00812-16 PG 9 WC Virology SC Virology GA DW6LH UT WOS:000383761900010 PM 27440881 ER PT J AU Iyer, SS Gangadhara, S Victor, B Shen, XY Chen, XM Nabi, R Kasturi, SP Sabula, MJ Labranche, CC Reddy, PBJ Tomaras, GD Montefiori, DC Moss, B Spearman, P Pulendran, B Kozlowski, PA Amara, RR AF Iyer, Smita S. Gangadhara, Sailaja Victor, Blandine Shen, Xiaoying Chen, Xuemin Nabi, Rafiq Kasturi, Sudhir P. Sabula, Michael J. Labranche, Celia C. Reddy, Pradeep B. J. Tomaras, Georgia D. Montefiori, David C. Moss, Bernard Spearman, Paul Pulendran, Bali Kozlowski, Pamela A. Amara, Rama Rao TI Virus-Like Particles Displaying Trimeric Simian Immunodeficiency Virus (SIV) Envelope gp160 Enhance the Breadth of DNA/Modified Vaccinia Virus Ankara SIV Vaccine-Induced Antibody Responses in Rhesus Macaques SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL RESPONSES; HIV VACCINE; MUCOSAL CHALLENGE; DENDRITIC CELLS; DNA/MVA VACCINE; PROTECTION; IMMUNOGENICITY; SIVMAC251; EFFICACY; IMMUNITY AB The encouraging results of the RV144 vaccine trial have spurred interest in poxvirus prime-protein boost human immunodeficiency virus (HIV) vaccine modalities as a strategy to induce protective immunity. Because vaccine-induced protective immunity is critically determined by HIV envelope (Env) conformation, significant efforts are directed toward generating soluble trimeric Env immunogens that assume native structures. Using the simian immunodeficiency virus (SIV)-macaque model, we tested the immunogenicity and efficacy of sequential immunizations with DNA(D), modified vaccinia virus Ankara (MVA) (M), and protein immunogens, all expressing virus-like particles (VLPs) displaying membrane-anchored trimeric Env. A single VLP protein boost displaying trimeric gp160 adjuvanted with nanoparticle-encapsulated Toll-like receptor 4/7/8 (TLR4/7/8) agonists, administered 44 weeks after the second MVA immunization, induced up to a 3-fold increase in Env-specific IgG binding titers in serum and mucosa. Importantly, the VLP protein boost increased binding antibody against scaffolded V1V2, antibody-dependent phagocytic activity against VLP-coated beads, and antibody breadth and neutralizing antibody titers against homologous and heterologous tier 1 SIVs. Following 5 weekly intrarectal SIVmac251 challenges, two of sevenDNA/MVA and VLP (DM + VLP)-vaccinated animals were completely protected compared to productive infection in all seven DM-vaccinated animals. Vaccinated animals demonstrated stronger acute viral pulldown than controls, but a trend for higher acute viremia was observed in the DM + VLP group, likely due to a slower recall of Gag-specific CD8 T cells. Our findings support immunization with VLPs containing trimeric Env as a strategy to augment protective antibody but underscore the need for optimal engagement of CD8 T cells to achieve robust early viral control. IMPORTANCE The development of an effective HIV vaccine remains a global necessity for preventing HIV infection and reducing the burden of AIDS. While this goal represents a formidable challenge, the modest efficacy of the RV144 trial indicates that multicomponent vaccination regimens that elicit both cellular and humoral immune responses can prevent HIV infection in humans. However, whether protein immunizations synergize withDNAprime-viral vector boosts to enhance cellular and humoral immune responses remains poorly understood. We addressed this question in a nonhuman primate model, and our findings show benefit for sequential protein immunization combined with a potent adjuvant in boosting antibody titers induced by a preceding DNA/MVA immunization. This promising strategy can be further developed to enhance neutralizing antibody responses and boost CD8 T cells to provide robust protection and viral control. C1 [Iyer, Smita S.; Gangadhara, Sailaja; Victor, Blandine; Sabula, Michael J.; Reddy, Pradeep B. J.; Amara, Rama Rao] Emory Univ, Yerkes Natl Primate Res Ctr, Emory Vaccine Ctr, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. [Shen, Xiaoying; Tomaras, Georgia D.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA. [Chen, Xuemin; Spearman, Paul] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA. [Nabi, Rafiq; Kozlowski, Pamela A.] Louisiana State Univ, Hlth Sci Ctr, Dept Microbiol Immunol & Parasitol, New Orleans, LA USA. [Kasturi, Sudhir P.; Pulendran, Bali] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Labranche, Celia C.; Montefiori, David C.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Moss, Bernard] NIAID, Viral Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RP Amara, RR (reprint author), Emory Univ, Yerkes Natl Primate Res Ctr, Emory Vaccine Ctr, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. EM ramara@emory.edu FU National Institute of Allergy and Infectious Diseases (NIAID) [P01 AI088575]; NIH [PO1 AI088575, P51 OD011132, P30 AI50409, HHSN27201100016C]; Division of Intramural Research, NIAID, NIH FX This work, including the efforts of Rama Rao Amara, was funded by National Institute of Allergy and Infectious Diseases (NIAID) (P01 AI088575).; This study was supported in part by NIH grants PO1 AI088575 to R.R.A., P51 OD011132 to the Yerkes National Primate Research Center, P30 AI50409 to the Emory Center for AIDS Research, and HHSN27201100016C to D.C.M. Partial support was also provided by the Division of Intramural Research, NIAID, NIH. NR 40 TC 1 Z9 1 U1 6 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD OCT PY 2016 VL 90 IS 19 BP 8842 EP 8854 DI 10.1128/JVI.01163-16 PG 13 WC Virology SC Virology GA DW6LH UT WOS:000383761900038 PM 27466414 ER PT J AU Sivan, G Weisberg, AS Americo, JL Moss, B AF Sivan, Gilad Weisberg, Andrea S. Americo, Jeffrey L. Moss, Bernard TI Retrograde Transport from Early Endosomes to the trans-Golgi Network Enables Membrane Wrapping and Egress of Vaccinia Virus Virions SO JOURNAL OF VIROLOGY LA English DT Article ID INTRACELLULAR ENVELOPED VIRIONS; COG COMPLEX INTERACTS; ACTIN-BASED MOTILITY; EXTRACELLULAR VIRUS; PHOSPHOLIPASE-D; F13L PROTEIN; TRAFFICKING INHIBITOR; SIRNA SCREEN; CELLS; RELEASE AB The anterograde pathway, from the endoplasmic reticulum through the trans-Golgi network to the cell surface, is utilized by trans-membrane and secretory proteins. The retrograde pathway, which directs traffic in the opposite direction, is used following endocytosis of exogenous molecules and recycling of membrane proteins. Microbes exploit both routes: viruses typically use the anterograde pathway for envelope formation prior to exiting the cell, whereas ricin and Shiga-like toxins and some nonenveloped viruses use the retrograde pathway for cell entry. Mining a human genome-wide RNA interference (RNAi) screen revealed a need for multiple retrograde pathway components for cell-to-cell spread of vaccinia virus. We confirmed and extended these results while discovering that retrograde trafficking was required for virus egress rather than entry. Retro-2, a specific retrograde trafficking inhibitor of protein toxins, potently prevented spread of vaccinia virus as well as monkeypox virus, a human pathogen. Electron and confocal microscopy studies revealed that Retro-2 prevented wrapping of virions with an additional double-membrane envelope that enables microtubular transport, exocytosis, and actin polymerization. The viral B5 and F13 protein components of this membrane, which are required for wrapping, normally colocalize in the trans-Golgi network. However, only B5 traffics through the secretory pathway, suggesting that F13 uses another route to the trans-Golgi network. The retrograde route was demonstrated by finding that F13 was largely confined to early endosomes and failed to colocalize with B5 in the presence of Retro-2. Thus, vaccinia virus makes novel use of the retrograde transport system for formation of the viral wrapping membrane. IMPORTANCE Efficient cell-to-cell spread of vaccinia virus and other orthopoxviruses depends on the wrapping of infectious particles with a double membrane that enables microtubular transport, exocytosis, and actin polymerization. Interference with wrapping or subsequent steps results in severe attenuation of the virus. Some previous studies had suggested that the wrapping membrane arises from the trans-Golgi network, whereas others suggested an origin from early endosomes. Some nonenveloped viruses use retrograde trafficking for entry into the cell. In contrast, we provided evidence that retrograde transport from early endosomes to the trans-Golgi network is required for the membrane-wrapping step in morphogenesis of vaccinia virus and egress from the cell. The potent in vitro inhibition of this step by the drug Retro-2 suggests that derivatives with enhanced pharmacological properties might serve as useful antipoxviral agents. C1 [Sivan, Gilad; Weisberg, Andrea S.; Americo, Jeffrey L.; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM bmoss@nih.gov OI Moss, Bernard/0000-0002-2154-8564 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases (DIR, NIAID) [1 ZIA AI001074] FX This work, including the efforts of Bernard Moss, was funded by Division of Intramural Research, National Institute of Allergy and Infectious Diseases (DIR, NIAID) (1 ZIA AI001074). NR 80 TC 3 Z9 3 U1 8 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD OCT PY 2016 VL 90 IS 19 BP 8891 EP 8905 DI 10.1128/JVI.01114-16 PG 15 WC Virology SC Virology GA DW6LH UT WOS:000383761900042 PM 27466413 ER PT J AU Chung, JY Choi, J Sears, JD Ylaya, K Perry, C Choi, CH Hong, SM Chol, H Brown, KM Hewitt, SM AF Chung, Joon-Yong Choi, Jiyeon Sears, John D. Ylaya, Kris Perry, Candice Choi, Chel H. Hong, Seung-Mo Chol, Hanbyoul Brown, Kevin M. Hewitt, Stephen M. TI A melanin-bleaching methodology for molecular and histopathological analysis of formalin-fixed paraffin-embedded tissue SO LABORATORY INVESTIGATION LA English DT Article ID PHASE PROTEIN ARRAY; PIGMENTED MELANOCYTIC NEOPLASMS; DILUTE HYDROGEN-PEROXIDE; GROWTH-FACTOR; RNA; REMOVAL; IMMUNOPEROXIDASE; POLYMERASE; EXTRACTION; DIAGNOSIS AB Removal of excessive melanin from heavily pigmented formalin-fixed paraffin-embedded (FFPE) melanoma tissues is essential for histomorphological and molecular diagnostic assessments. Although there have been efforts to address this issue, current methodologies remain complex and time-consuming, and are not suitable for multiple molecular applications. Herein, we have developed a robust and rapid melanin-bleaching methodology for FFPE tissue specimens. Our approach is based on quick bleaching (15 min) at high temperature (80 degrees C) with 0.5% diluted hydrogen peroxide (H2O2) in Tris-HCl, PBS, or Tris/Tricine/SDS buffer. Immunostaining for Ki-67 and HMB45 was enhanced by bleaching with 0.5% H2O2 in Tris/Tricine/SDS and Tris-HCl, respectively. In addition to histopathological applications, our approach also facilitates recovery of protein and nucleic acid from archival melanin-rich FFPE tissue sections. Protein extracted from bleached FFPE tissues was compatible with western blotting using anti-human GAPDH and AKT antibodies. Our bleaching condition significantly improved RNA quality compared with unbleached tissues without compromising the yield. Notably, the RNA/DNA obtained from bleached tissues was suitable for end point PCR and real-time quantitative RT-PCR. In conclusion, this improved melanin-bleaching method enhances and simplifies immunostaining procedures, and facilitates the use of melanin-rich FFPE tissues for histomorphological and PCR amplification-based molecular assays. C1 [Chung, Joon-Yong; Sears, John D.; Ylaya, Kris; Perry, Candice; Choi, Chel H.; Chol, Hanbyoul; Hewitt, Stephen M.] NCI, Expt Pathol Lab, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Choi, Jiyeon; Brown, Kevin M.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Perry, Candice] Leidos Biomed Res Inc, Antibody Characterizat Lab, Adv Technol Program, Frederick, MD USA. [Choi, Chel H.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Obstet & Gynecol, Seoul, South Korea. [Hong, Seung-Mo] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul, South Korea. [Chol, Hanbyoul] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Obstet & Gynecol, Seoul, South Korea. RP Hewitt, SM (reprint author), NCI, Expt Pathol Lab, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.; Hewitt, SM (reprint author), NCI, Expt Pathol Lab, Pathol Lab, Ctr Canc Res,NIH, MSC1500, Bethesda, MD 20892 USA. EM genejock@helix.nih.gov OI Chung, Joon-Yong/0000-0001-5041-5982 FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, and Division of Cancer Epidemiology and Genetics FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, and Division of Cancer Epidemiology and Genetics. NR 30 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 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD OCT PY 2016 VL 96 IS 10 BP 1116 EP 1127 DI 10.1038/labinvest.2016.90 PG 12 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA DX0EV UT WOS:000384035500007 PM 27548802 ER PT J AU Burbelo, PD Iadarola, MJ Alevizos, I Sapio, MR AF Burbelo, Peter D. Iadarola, Michael J. Alevizos, Ilias Sapio, Matthew R. TI Transcriptomic Segregation of Human Autoantigens Useful for the Diagnosis of Autoimmune Diseases SO MOLECULAR DIAGNOSIS & THERAPY LA English DT Review ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PRIMARY BILIARY-CIRRHOSIS; STIFF-PERSON SYNDROME; I INTERFERON PATHWAY; RHEUMATOID-ARTHRITIS; DERMATITIS-HERPETIFORMIS; SJOGRENS-SYNDROME; MEMBRANOUS NEPHROPATHY; MICROARRAY ANALYSIS; CELIAC-DISEASE AB The measurement of autoantibodies in the clinical care of autoimmune patients allows for diagnosis, monitoring, and even disease prediction. Despite their clinical utility, the functional significance of autoantibody target proteins in many autoimmune diseases remains unclear. Here we present a comprehensive review of 52 autoantigens commonly employed for the serological diagnosis of 24 autoimmune diseases. We discuss their function, whether they have extracellular-exposed epitopes, and whether antibodies to these proteins are known to be pathogenic. Transcriptomics (RNA-Seq) datasets were mined to display messenger RNA (mRNA) expression of the autoantigens across 32 tissues and organs. This analysis revealed that autoantigens cluster into one of three groups: expression in the tissue most strongly affected in the disease (Group I), ubiquitous expression with enrichment in immune tissues (Group II), or expression in other tissues not typically associated with the clinical presentation (Group III). Clustering demonstrated that the autoantigens within Group I were often proteins containing extracellular epitopes, many of which are targets of pathogenic autoantibodies. Group II autoantigens were targets for several rheumatological diseases, including Sjogren syndrome, systemic lupus erythematosus, myositis, and systemic sclerosis, and were ubiquitously expressed with enrichment in immune-rich tissues. This raises the possibility that immune cells in Group II disorders may be the source of autoimmunization and/or targets of immune cell responses. Since tissues showing enriched autoantigen gene expression may contribute to the development of autoantibodies and subsequent autoimmunity, the emergent patterns arising from the autoantigen transcriptomic profiles may provide a new heuristic framework to deconvolute these complex disorders. C1 [Burbelo, Peter D.] Natl Inst Dent & Craniofacial Res, Dent Clin Res Core, NIH, Bldg 10,Rm 5N102, Bethesda, MD 20892 USA. [Iadarola, Michael J.; Sapio, Matthew R.] NIH, Dept Perioperat Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. [Alevizos, Ilias] Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome & Salivary Gland Dysfunct Unit, NIH, Bethesda, MD USA. RP Burbelo, PD (reprint author), Natl Inst Dent & Craniofacial Res, Dent Clin Res Core, NIH, Bldg 10,Rm 5N102, Bethesda, MD 20892 USA. EM burbelop@nidcr.nih.gov FU intramural research programs of the National Institute of Dental and Craniofacial Research; National Institutes of Health Clinical Center FX This work was supported by the intramural research programs of the National Institute of Dental and Craniofacial Research and the National Institutes of Health Clinical Center. NR 76 TC 0 Z9 0 U1 4 U2 4 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 1177-1062 EI 1179-2000 J9 MOL DIAGN THER JI Mol. Diagn. Ther. PD OCT PY 2016 VL 20 IS 5 BP 415 EP 427 DI 10.1007/s40291-016-0211-6 PG 13 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA DW3BE UT WOS:000383516300002 PM 27259330 ER PT J AU Chen, W Liu, P Volkow, ND Pan, Y Du, C AF Chen, W. Liu, P. Volkow, N. D. Pan, Y. Du, C. TI Cocaine attenuates blood flow but not neuronal responses to stimulation while preserving neurovascular coupling for resting brain activity SO MOLECULAR PSYCHIATRY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; RAT SOMATOSENSORY CORTEX; FUNCTIONAL MRI; IN-VIVO; ALPHA-CHLORALOSE; DOPAMINE; ABUSERS; SIGNAL; ABNORMALITIES; COMPLICATIONS AB Cocaine affects neuronal activity and constricts cerebral blood vessels, making it difficult to determine whether cocaine-induced changes in cerebral blood flow (CBF) reflect neuronal activation or its vasoactive effects. Here we assessed the effects of acute cocaine on both resting-state and stimulation responses to investigate cocaine's effects on neurovascular coupling and to differentiate its effects on neuronal activity from its vasoactive actions. We concurrently measured cortical field potentials via thinned-skull electroencephalography recordings and CBF with laser Doppler flowmetry in the rat's somatosensory cortex for both resting state and forepaw stimulation before and following cocaine administration (1 mg kg(-1), intravenously). Results show both resting-state field potentials and CBF were depressed after cocaine administration (19.8 +/- 4.7% and 52.1 +/- 13.4%, respectively) and these changes were strongly correlated with each other (r = 0.81, P<0.001), indicating that cocaine did not affect neurovascular coupling at rest and that the reduction in resting CBF reflected reduction in synchronized spontaneous neuronal activity rather than vasoconstriction. In contrast, the forepaw stimulation-evoked neuronal activity was not changed by cocaine (P = 0.244), whereas the CBF to the stimulation was reduced 49.9 +/- 2.6% (P = 0.028) gradually recovering similar to 20 min after cocaine injection, indicating that neurovascular coupling during stimulation was temporarily disrupted by cocaine. Neurovascular uncoupling by cocaine during stimulation but not during rest indicates that distinct processes might underlie neurovascular regulation for both stimulation and spontaneous activity. The greater reductions by cocaine to the stimulation-induced CBF increases than to the background CBF should be considered when interpreting functional MRI studies comparing activation responses between controls and cocaine abusers. Neurovascular uncoupling could contribute to cocaine's neurotoxicity, particularly for stimulation conditions when CBF might be insufficient to cover for the energetic demands of neuronal tissue. C1 [Chen, W.; Liu, P.; Pan, Y.; Du, C.] SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA. [Volkow, N. D.] NIAAA, NIH, Bethesda, MD 20892 USA. RP Pan, Y; Du, C (reprint author), SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA.; Volkow, ND (reprint author), NIAAA, NIH, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov; yingtian.pan@stonybrook.edu; congwu.du@stonybrook.edu FU National Institutes of Health (NIH) [R21DA032228, 1R01DA029718, R01NS084817]; NIH's Intramural Program FX This work was supported, in part, by National Institutes of Health (NIH) Grants R21DA032228 (YP/CD), 1R01DA029718 (CD/YP), R01NS084817 (CD) and NIH's Intramural Program (NDV). NR 47 TC 2 Z9 2 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD OCT PY 2016 VL 21 IS 10 BP 1408 EP 1416 DI 10.1038/mp.2015.185 PG 9 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA DX1KT UT WOS:000384127000012 PM 26666202 ER PT J AU Belinson, H Nakatani, J Babineau, BA Birnbaum, RY Ellegood, J Bershteyn, M McEvilly, RJ Long, JM Willert, K Klein, OD Ahituv, N Lerch, JP Rosenfeld, MG Wynshaw-Boris, A AF Belinson, H. Nakatani, J. Babineau, B. A. Birnbaum, R. Y. Ellegood, J. Bershteyn, M. McEvilly, R. J. Long, J. M. Willert, K. Klein, O. D. Ahituv, N. Lerch, J. P. Rosenfeld, M. G. Wynshaw-Boris, A. TI Prenatal beta-catenin/Brn2/Tbr2 transcriptional cascade regulates adult social and stereotypic behaviors SO MOLECULAR PSYCHIATRY LA English DT Article ID AUTISM SPECTRUM DISORDERS; NEURONAL DIFFERENTIATION; INTERMEDIATE PROGENITORS; DEVELOPING NEOCORTEX; GENE-EXPRESSION; MOUSE MODELS; BETA-CATENIN; PATHWAY; CELLS; BRAIN AB Social interaction is a fundamental behavior in all animal species, but the developmental timing of the social neural circuit formation and the cellular and molecular mechanisms governing its formation are poorly understood. We generated a mouse model with mutations in two Disheveled genes, Dvl1 and Dvl3, that displays adult social and repetitive behavioral abnormalities associated with transient embryonic brain enlargement during deep layer cortical neuron formation. These phenotypes were mediated by the embryonic expansion of basal neural progenitor cells (NPCs) via deregulation of a a-catenin/Brn2/Tbr2 transcriptional cascade. Transient pharmacological activation of the canonical Wnt pathway during this period of early corticogenesis rescued the beta-catenin/Brn2/Tbr2 transcriptional cascade and the embryonic brain phenotypes. Remarkably, this embryonic treatment prevented adult behavioral deficits and partially rescued abnormal brain structure in Dvl mutant mice. Our findings define a mechanism that links fetal brain development and adult behavior, demonstrating a fetal origin for social and repetitive behavior deficits seen in disorders such as autism. C1 [Belinson, H.; Nakatani, J.; Babineau, B. A.; Bershteyn, M.; Wynshaw-Boris, A.] Univ Calif San Francisco, Sch Med, Dept Pediat, Inst Human Genet,Edyth & Eli Broad Inst Regenerat, San Francisco, CA USA. [Birnbaum, R. Y.] Ben Gurion Univ Negev, Dept Life Sci, Beer Sheva, Israel. [Ellegood, J.; Lerch, J. P.] Hosp Sick Children, Mouse Imaging Ctr, Toronto, ON, Canada. [McEvilly, R. J.; Rosenfeld, M. G.] Univ Calif San Diego, Sch Med, Howard Hughes Med Inst, Dept Med, La Jolla, CA 92093 USA. [Long, J. M.] NIA, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA. [Willert, K.] Univ Calif San Diego, Sch Med, Inst Regenerat Med, Dept Cell & Mol Biol, La Jolla, CA 92093 USA. [Klein, O. D.] Univ Calif San Francisco, Dept Orofacial Sci, San Francisco, CA 94143 USA. [Klein, O. D.] Univ Calif San Francisco, Program Craniofacial & Mesenchymal Biol, San Francisco, CA 94143 USA. [Ahituv, N.] Univ Calif San Francisco, Inst Human Genet, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. [Lerch, J. P.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. [Wynshaw-Boris, A.] Case Western Reserve Univ, Sch Med, Dept Genet & Genome Sci, 10900 Euclid Ave,BRB731, Cleveland, OH 44106 USA. RP Wynshaw-Boris, A (reprint author), Case Western Reserve Univ, Sch Med, Dept Genet & Genome Sci, 10900 Euclid Ave,BRB731, Cleveland, OH 44106 USA. EM ajw168@case.edu FU NINDS [R01 NS073159, R01NS079231]; Simons Foundation SFARI [256769]; Ontario Brain Institute; Autism Speaks Translational Postdoctoral Fellowship [7587]; NIH [P30NS065780]; NIH, National Institute on Aging FX This research was supported by NINDS grants R01 NS073159 (AWB) and R01NS079231 (RYB & NA), the Simons Foundation SFARI #256769 (NA), the Ontario Brain Institute (JPL), and a Autism Speaks Translational Postdoctoral Fellowship #7587 (HB). Behavioral data were obtained with the help of the Gladstone Institute Behavioral Core (supported by NIH grant P30NS065780). This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. We thank Peter Scacheri for his critical comments on the manuscript. NR 71 TC 4 Z9 4 U1 10 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD OCT PY 2016 VL 21 IS 10 BP 1417 EP 1433 DI 10.1038/mp.2015.207 PG 17 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA DX1KT UT WOS:000384127000013 PM 26830142 ER PT J AU Mastronardi, CA Pillai, E Pineda, DA Martinez, AF Lopera, F Velez, JI Palacio, JD Patel, H Easteal, S Acosta, MT Castellanos, FX Muenke, M Arcos-Burgos, M AF Mastronardi, C. A. Pillai, E. Pineda, D. A. Martinez, A. F. Lopera, F. Velez, J. I. Palacio, J. D. Patel, H. Easteal, S. Acosta, M. T. Castellanos, F. X. Muenke, M. Arcos-Burgos, M. TI Linkage and association analysis of ADHD endophenotypes in extended and multigenerational pedigrees from a genetic isolate SO MOLECULAR PSYCHIATRY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; FAMILY-BASED ASSOCIATION; GENERAL-CLASS; SUSCEPTIBILITY; EPILEPSY; CHILDREN; TRAITS; TESTS; POWER; LOCI AB Attention-deficit/hyperactivity disorder (ADHD) is a heritable, chronic, neurodevelopmental disorder with serious long-term repercussions. Despite being one of the most common cognitive disorders, the clinical diagnosis of ADHD is based on subjective assessments of perceived behaviors. Endophenotypes (neurobiological markers that cosegregate and are associated with an illness) are thought to provide a more powerful and objective framework for revealing the underlying neurobiology than syndromic psychiatric classification. Here, we present the results of applying genetic linkage and association analyses to neuropsychological endophenotypes using microsatellite and single nucleotide polymorphisms. We found several new genetic regions linked and/or associated with these endophenotypes, and others previously associated to ADHD, for example, loci harbored in the LPHN3, FGF1, POLR2A, CHRNA4 and ANKFY1 genes. These findings, when compared with those linked and/or associated to ADHD, suggest that these endophenotypes lie on shared pathways. The genetic information provided by this study offers a novel and complementary method of assessing the genetic causes underpinning the susceptibility to behavioral conditions and may offer new insights on the neurobiology of the disorder. C1 [Mastronardi, C. A.; Pillai, E.; Velez, J. I.; Patel, H.; Arcos-Burgos, M.] Australian Natl Univ, John Curtin Sch Med Res, Genome Biol Dept, ANU Coll Med Biol & Environm,Genom & Predict Med, Bldg 131 Garran Rd, Canberra, ACT 2600, Australia. [Pineda, D. A.; Lopera, F.; Palacio, J. D.; Arcos-Burgos, M.] Univ Antioquia, Grp Neurosci, Medellin, Colombia. [Martinez, A. F.; Acosta, M. T.; Muenke, M.; Arcos-Burgos, M.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Easteal, S.] Australian Natl Univ, John Curtin Sch Med Res, Genome Biol Dept,Genom, ANU Coll Med Biol & Environm,Natl Ctr Indigenous, Canberra, ACT, Australia. [Castellanos, F. X.] NYU, Ctr Child Study, Langone Med Ctr, New York, NY USA. [Castellanos, F. X.] Nathan S Kline Inst Psychiat Res, Orangeburg, NY USA. RP Arcos-Burgos, M (reprint author), Australian Natl Univ, John Curtin Sch Med Res, Genome Biol Dept, ANU Coll Med Biol & Environm,Genom & Predict Med, Bldg 131 Garran Rd, Canberra, ACT 2600, Australia.; Muenke, M; Arcos-Burgos, M (reprint author), NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. EM mamuenke@mail.nih.gov; Mauricio.Arcos-Burgos@anu.edu.au OI Castellanos, Francisco/0000-0001-9192-9437 FU John Curtin School of Medical Research, ANU College of Medicine, Biology and Environment, The Australian National University, Canberra, ACT, Australia [R42100-12]; Division of Intramural Research, National Human Genome Research Institutes, National Institutes of Health, Bethesda, MD, USA; NHGRI-NIH; COLCIENCIAS [1115-04-18083, 459-2005]; University of Antioquia; University of San Buenaventura FX Claudio Mastronardi, Eva Pillai and Mauricio Arcos-Burgos are supported by John Curtin School of Medical Research, ANU College of Medicine, Biology and Environment, The Australian National University, Canberra, ACT, Australia, Project R42100-12. Maximilian Muenke, Ariel F Martinez, Maria T Acosta and Mauricio Arcos-Burgos are supported by the Division of Intramural Research, National Human Genome Research Institutes, National Institutes of Health, Bethesda, MD, USA. Part of this research was funded by the NHGRI-NIH and by COLCIENCIAS which funded the Project: 'Genetica del Trastorno de Atencion-Hiperactividad: los fenotipos complejos, los endofenotipos y la asociacion con genes mayores y de susceptibilidad' Code: 1115-04-18083, Contract: 459-2005, to David Pineda, University of Antioquia and University of San Buenaventura. NR 32 TC 2 Z9 2 U1 10 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD OCT PY 2016 VL 21 IS 10 BP 1434 EP 1440 DI 10.1038/mp.2015.172 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA DX1KT UT WOS:000384127000014 PM 26598068 ER PT J AU Zimmet, P Alberti, KG Magliano, DJ Bennett, PH AF Zimmet, Paul Alberti, K. George Magliano, Dianna J. Bennett, Peter H. TI Diabetes mellitus statistics on prevalence and mortality: facts and fallacies SO NATURE REVIEWS ENDOCRINOLOGY LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; ALL-CAUSE MORTALITY; FASTING GLUCOSE; DIAGNOSTIC-CRITERIA; EXCESS MORTALITY; POOLED ANALYSIS; GLOBAL BURDEN; LIFE-STYLE; POPULATION; RISK AB Diabetes mellitus is one of the most important public health challenges of the twenty-first century. Until the past decade, it has been seriously underrated as a global health threat. Major gaps exist in efforts to comprehend the burden nationally and globally, especially in developing nations, due to a lack of accurate data for monitoring and surveillance. Early attempts to obtain accurate data, discussed in this article, seem to have been cast aside so, at present, these needs remain unmet. Existing international efforts to assemble information fall far short of requirements. Current estimates are imprecise, only providing a rough picture, and probably underestimate the disease burden. The methodologies that are currently used, and that are discussed in this Perspectives article, are inadequate for providing a complete and accurate assessment of the prevalence of diabetes mellitus. International consensus on uniform standards and criteria for reporting national data on diabetes mellitus prevalence as well as for common complications of diabetes mellitus and mortality need to be developed. C1 [Zimmet, Paul] Monash Univ, Fac Med Nursing & Hlth Sci, 99 Commercial Rd, Melbourne, Vic 3004, Australia. [Alberti, K. George] Imperial Coll, Dept Endocrinol & Metab, St Marys Campus,Norfolk Pl, London W2 1PG, England. [Magliano, Dianna J.] Baker IDI Heart & Diabet Inst, 99 Commercial Rd, Melbourne, Vic 3004, Australia. [Bennett, Peter H.] NIH, 1550 East Indian Sch Rd, Phoenix, AZ 85014 USA. RP Zimmet, P (reprint author), Monash Univ, Fac Med Nursing & Hlth Sci, 99 Commercial Rd, Melbourne, Vic 3004, Australia. EM paul.zimmet@monash.edu NR 59 TC 4 Z9 4 U1 18 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5029 EI 1759-5037 J9 NAT REV ENDOCRINOL JI Nat. Rev. Endocrinol. PD OCT PY 2016 VL 12 IS 10 BP 616 EP 622 DI 10.1038/nrendo.2016.105 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DW7AR UT WOS:000383803900007 PM 27388988 ER PT J AU Usdin, TB Dimitrov, EL AF Usdin, Ted B. Dimitrov, Eugene L. TI The Effects of Extended Pain on Behavior: Recent Progress SO NEUROSCIENTIST LA English DT Review DE Pain-related behavior; neuropathic pain; inflammatory pain; chronic pain; pain model; affective pain ID PERIPHERAL-NERVE INJURY; ANTERIOR CINGULATE CORTEX; MEDIAL PREFRONTAL CORTEX; CHRONIC NEUROPATHIC PAIN; ANXIETY-LIKE BEHAVIOR; NUCLEUS-ACCUMBENS; PERSISTENT PAIN; CENTRAL AMYGDALA; WORKING-MEMORY; UP-REGULATION AB Chronic pain is frequently associated with anxiety, depression, and cognitive dysfunction. This review discusses recent work in rodents that contributes to the understanding of their neurobiological links. Brain regions that contain circuits that mediate persistent changes in behavior that are caused by nerve injury or joint inflammation include the rostral anterior cingulate and other parts of the medial prefrontal cortex, the basolateral and central nucleus of the amygdala, and the nucleus accumbens. Functional changes, including increases in the activity within specific neuronal pathways and in the levels of specific synaptic components, that are associated with the behavior changes, or are in some cases necessary for them, have recently been identified. Broadly projecting modulatory systems and widely expressed factors such as cytokines and growth factors also contribute to pain-associated behavior. Integrating these observations and determining their causal relationships is now critical for the identification of therapeutic targets and the design of appropriate interventions. C1 [Usdin, Ted B.] NIMH, Sect Fundamental Neurosci, Intramural Res Program, Bethesda, MD 20892 USA. [Dimitrov, Eugene L.] Rosalind Franklin Univ Med & Sci, Dept Physiol & Biophys, N Chicago, IL USA. RP Usdin, TB (reprint author), NIMH, Sect Fundamental Neurosci, Intramural Res Program, Bethesda, MD 20892 USA. EM usdint@mail.nih.gov FU NIMH Intramural Program [ZIA-MH002685] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Support was provided by the NIMH Intramural Program (ZIA-MH002685). NR 66 TC 1 Z9 1 U1 8 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 EI 1089-4098 J9 NEUROSCIENTIST JI Neuroscientist PD OCT PY 2016 VL 22 IS 5 BP 521 EP 533 DI 10.1177/1073858416633104 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DV6DC UT WOS:000383020100012 PM 27621368 ER PT J AU Kahler, CW Caswell, AJ Laws, MB Walthers, J Magill, M Mastroleo, NR Howe, CJ Souza, T Wilson, I Bryant, K Monti, PM AF Kahler, Christopher W. Caswell, Amy J. Laws, M. Barton Walthers, Justin Magill, Molly Mastroleo, Nadine R. Howe, Chanelle J. Souza, Timothy Wilson, Ira Bryant, Kendall Monti, Peter M. TI Using topic coding to understand the nature of change language in a motivational intervention to reduce alcohol and sex risk behaviors in emergency department patients SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Alcohol; Sex risk; HIV; Motivational interviewing; Dialogue coding ID USE DISORDERS; HIV CARE; COMMITMENT LANGUAGE; MIXED METHODS; USE OUTCOMES; METAANALYSIS; AGREEMENT AB Objective: To elucidate patient language that supports changing a health behavior (change talk) or sustaining the behavior (sustain talk). Methods: We developed a novel coding system to characterize topics of patient speech in a motivational intervention targeting alcohol and HIV/sexual risk in 90 Emergency Department patients. We further coded patient language as change or sustain talk. Results: For both alcohol and sex, discussions focusing on benefits of behavior change or change planning were most likely to involve change talk, and these topics comprised a large portion of all change talk. Greater discussion of barriers and facilitators of change also was associated with more change talk. For alcohol use, benefits of drinking behavior was the most common topic of sustain talk. For sex risk, benefits of sexual behavior were rarely discussed, and sustain talk centered more on patterns and contexts, negations of drawbacks, and drawbacks of sexual risk behavior change. Conclusions: Topic coding provided unique insights into the content of patient change and sustain talk. Practice implications: Patients are most likely to voice change talk when conversation focuses on behavior change rather than ongoing behavior. Interventions addressing multiple health behaviors should address the unique motivations for maintaining specific risky behaviors. (C) 2016 Elsevier Ireland Ltd. All rights reserved. C1 [Kahler, Christopher W.; Caswell, Amy J.; Walthers, Justin; Magill, Molly; Mastroleo, Nadine R.; Souza, Timothy; Monti, Peter M.] Brown Univ, Ctr Alcohol & Addict Studies, Sch Publ Hlth, Providence, RI 02912 USA. [Laws, M. Barton; Wilson, Ira] Brown Univ, Sch Publ Hlth, Dept Hlth Serv Policy & Practice, Providence, RI 02912 USA. [Howe, Chanelle J.] Brown Univ, Sch Publ Hlth, Dept Epidemiol, Ctr Populat Hlth & Clin Epidemiol, Providence, RI 02912 USA. [Bryant, Kendall] Natl Inst Alcohol Abuse & Alcoholism, 5635 Fishers Lane, Bethesda, MD USA. RP Kahler, CW (reprint author), Brown Univ, Sch Publ Hlth, Ctr Alcohol & Addict Studies, Dept Behav & Social Sci, Box G-S121-4, Providence, RI 02912 USA. EM Christopher_Kahler@brown.edu FU National Institute on Alcohol Abuse and Alcoholism (NIAAA) [U24AA022003, 5R01AA009892-20, P01AA019072, K23AA018126] FX Support for this work was provided by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), grants U24AA022003, 5R01AA009892-20, P01AA019072, and K23AA018126. Dr. Bryant from NIAAA was involved in conceptualizing and writing this manuscript. NIAAA did not have any other involvement in the project. NR 30 TC 0 Z9 0 U1 6 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD OCT PY 2016 VL 99 IS 10 BP 1595 EP 1602 DI 10.1016/j.pec.2016.05.003 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA DW0VQ UT WOS:000383361500008 PM 27161165 ER PT J AU Zweidler-McKay, PA Hogan, MJS Jubran, R Black, V Casillas, J Harper, J Malempati, S Margolin, J Felgenhauer, J Sakamoto, KM Franklin, J Shah, M Seibel, N Buchanan, G Vaiselbuh, SR Hastings, C Hilden, J Stork, LC AF Zweidler-McKay, Patrick A. Hogan, Mary-Jane Staba Jubran, Rima Black, Vandy Casillas, Jacqueline Harper, James Malempati, Suman Margolin, Judith Felgenhauer, Judy Sakamoto, Kathleen M. Franklin, Janet Shah, Mona Seibel, Nita Buchanan, George Vaiselbuh, Sarah R. Hastings, Caroline Hilden, Joanne Stork, Linda C. TI Navigating your career path in pediatric hematology/oncology: On and off the beaten track SO PEDIATRIC BLOOD & CANCER LA English DT Article C1 [Zweidler-McKay, Patrick A.] Univ Texas MD Anderson Canc Ctr, Childrens Canc Hosp, Div Pediat, Houston, TX 77030 USA. [Hogan, Mary-Jane Staba] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. [Jubran, Rima] Childrens Hosp Los Angeles, Div Hematol Oncol, Los Angeles, CA 90027 USA. [Black, Vandy] Univ Florida, Coll Med, Dept Pediat, Pediat, Gainesville, FL USA. [Casillas, Jacqueline] Univ Calif Los Angeles, Los Angeles Mattel Childrens Hosp, Div Hematol Oncol, Los Angeles, CA USA. [Harper, James] Univ Nebraska Med Ctr, Dept Pediat, Omaha, NE USA. [Malempati, Suman; Stork, Linda C.] Oregon Hlth & Sci Univ, Doernbecher Childrens Hosp, Div Hematol Oncol, Portland, OR 97201 USA. [Margolin, Judith; Shah, Mona] Texas Childrens Hosp, Baylor Coll Med, Div Hematol Oncol, Houston, TX 77030 USA. [Felgenhauer, Judy] Providence Sacred Heart Med Ctr, Spokane, WA USA. [Felgenhauer, Judy] Childrens Hosp, Pediat, Spokane, WA USA. [Sakamoto, Kathleen M.] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA. [Franklin, Janet] Amgen Inc, Thousand Oaks, CA USA. [Seibel, Nita] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Buchanan, George] Univ Texas Southwestern Med Ctr Dallas, Dept Pediat, Dallas, TX USA. [Vaiselbuh, Sarah R.] Staten Isl Univ Ctr Northwell Hlth, Childrens Canc Ctr, Staten Isl, NY USA. [Hastings, Caroline] Childrens Hosp & Res Ctr, Div Hematol Oncol, Oakland, CA USA. [Hilden, Joanne] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO USA. RP Stork, LC (reprint author), OHSU, CDRCP, Dept Pediat, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM storkl@ohsu.edu NR 0 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD OCT PY 2016 VL 63 IS 10 BP 1723 EP 1730 DI 10.1002/pbc.26094 PG 8 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA DW0ZE UT WOS:000383371500006 PM 27295503 ER PT J AU Kang, MH Reynolds, CP Kolb, EA Gorlick, R Carol, H Lock, R Keir, ST Maris, JM Wu, JR Lyalin, D Kurmasheva, RT Houghton, PJ Smith, MA AF Kang, Min H. Reynolds, C. Patrick Kolb, E. Anders Gorlick, Richard Carol, Hernan Lock, Richard Keir, Stephen T. Maris, John M. Wu, Jianwrong Lyalin, Dmitry Kurmasheva, Raushan T. Houghton, Peter J. Smith, Malcolm A. TI Initial Testing (Stage 1) of MK-8242A Novel MDM2 Inhibitorby the Pediatric Preclinical Testing Program SO PEDIATRIC BLOOD & CANCER LA English DT Article DE developmental therapeutics; pi3k inhibitor; preclinical testing ID ACUTE LYMPHOBLASTIC-LEUKEMIA; PHASE-I TRIAL; SOLID TUMORS; P53 PATHWAY; DEDIFFERENTIATED LIPOSARCOMA; ANTAGONIST RG7112; XENOGRAFT MODELS; TP53 MUTATIONS; CHILDHOOD; CANCER AB BackgroundMK-8242 is an inhibitor of MDM2 that stabilizes the tumor suppressor TP53 and induces growth arrest or apoptosis downstream of TP53 induction. ProceduresMK-8242 was tested against the Pediatric Preclinical Testing Program (PPTP) in vitro cell line panel at concentrations from 1.0 nM to 10.0 M and against the PPTP in vivo xenograft panels using oral gavage on Days 1-5 and Day 15-19 at a dose of 125 mg/kg (solid tumors) or 75 mg/kg (acute lymphoblastic leukemia [ALL] models). ResultsThe median IC50 for MK-8242 was 0.07 M for TP53 wild-type cell lines versus >10 M for TP53 mutant cell lines. MK-8242 induced a twofold or greater delay in time to event in 10 of 17 (59%) of TP53 wild-type solid tumor xenografts, excluding osteosarcoma xenografts that have very low TP53 expression. Objective responses were observed in seven solid tumor xenografts representing multiple histotypes. For the systemic-disease ALL panel, among eight xenografts there were two complete responses (CRs) and six partial responses (PRs). Two additional MLL-rearranged xenografts (MV4;11 and RS4;11) grown subcutaneously showed maintained CR and PR, respectively. The expected pharmacodynamic responses to TP53 activation were observed in TP53 wild-type models treated with MK-8242. Pharmacokinetic analysis showed that MK-8242 drug exposure in SCID mice appears to exceed that was observed in adult phase 1 trials. ConclusionsMK-8242-induced tumor regressions across multiple solid tumor histotypes and induced CRs or PRs for most ALL xenografts. This activity was observed at MK-8242 drug exposures that appear to exceed those observed in human phase 1 trials. C1 [Kang, Min H.; Reynolds, C. Patrick] Texas Tech Univ, Hlth Sci Ctr, Ctr Canc, 3601 4th St STOP 9445, Lubbock, TX 79430 USA. [Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE USA. [Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA. [Carol, Hernan; Lock, Richard] Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia. [Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA. [Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA. [Maris, John M.] Abramson Family Canc Res Inst, Philadelphia, PA USA. [Wu, Jianwrong] St Jude Childrens Res Hosp, 332 N Lauderdale St, Memphis, TN 38105 USA. [Lyalin, Dmitry; Kurmasheva, Raushan T.; Houghton, Peter J.] Nationwide Childrens Hosp, Columbus, OH USA. [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Kang, MH (reprint author), Texas Tech Univ, Hlth Sci Ctr, Ctr Canc, 3601 4th St STOP 9445, Lubbock, TX 79430 USA. EM min.kang@ttuhsc.edu RI Lock, Richard/G-4253-2013; OI Reynolds, C. Patrick/0000-0002-2827-8536 FU National Cancer Institute [NO1-CM-42216, CA21765, CA108786] FX Grant sponsor: National Cancer Institute; Grant numbers: NO1-CM-42216, CA21765, and CA108786. NR 41 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD OCT PY 2016 VL 63 IS 10 BP 1744 EP 1752 DI 10.1002/pbc.26064 PG 9 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA DW0ZE UT WOS:000383371500009 PM 27238606 ER PT J AU Stewart, DR Givens, SS Harris, AK Williams, GM Messinger, YH Schultz, KAP Hill, DA AF Stewart, Douglas R. Givens, Shannon S. Harris, Anne K. Williams, Gretchen M. Messinger, Yoav H. Schultz, Kris Ann P. Hill, D. Ashley TI Comment on: DICER1-Negative Pleuropulmonary Blastoma in a Patient With Selective IgA Deficiency SO PEDIATRIC BLOOD & CANCER LA English DT Letter ID PREVALENCE; MUTATIONS C1 [Stewart, Douglas R.; Givens, Shannon S.] NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, NIH, Rockville, MD USA. [Harris, Anne K.; Williams, Gretchen M.; Messinger, Yoav H.; Schultz, Kris Ann P.] Childrens Hosp & Clin Minnesota, Dept Canc & Blood Disorders, Minneapolis, MN USA. [Harris, Anne K.; Williams, Gretchen M.; Messinger, Yoav H.; Schultz, Kris Ann P.] Int Pleuropulm Blastoma Registry, Minneapolis, MN USA. [Harris, Anne K.; Schultz, Kris Ann P.] Int Ovarian & Testicular Stromal Tumor Registry, Minneapolis, MN USA. [Hill, D. Ashley] Childrens Natl Hlth Syst, Med Genet Res Ctr, Div Pathol, Washington, DC USA. [Hill, D. Ashley] George Washington Univ, Sch Med & Hlth Sci, Dept Integrat Syst Biol, Washington, DC 20052 USA. RP Stewart, DR (reprint author), NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, NIH, 9609 Med Ctr Dr,Rm 6E450, Bethesda, MD 20892 USA. EM drstewart@mail.nih.gov FU NCI NIH HHS [R01 CA143167] NR 9 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD OCT PY 2016 VL 63 IS 10 BP 1869 EP 1870 DI 10.1002/pbc.26075 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA DW0ZE UT WOS:000383371500031 PM 27238822 ER PT J AU Csermely, P Korcsmaros, T Nussinov, R AF Csermely, Peter Korcsmaros, Tamas Nussinov, Ruth TI Intracellular and intercellular signaling networks in cancer initiation, development and precision anti-cancer therapy RAS acts as contextual signaling hub SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Review DE Cancer attractors; Cancer stem cells; Combination therapies; N=1 trials; RAS; Signaling networks ID TUMOR MICROENVIRONMENT; CELL; PATHWAY; METASTASIS; EFFECTOR; DYNAMICS; MODELS; DIFFERENTIATION; HETEROGENEITY; PROLIFERATION AB Cancer initiation and development are increasingly perceived as systems-level phenomena, where intraand inter-cellular signaling networks of the ecosystem of cancer and stromal cells offer efficient methodologies for outcome prediction and intervention design. Within this framework, RAS emerges as a 'contextual signaling hub', i.e. the final result of RAS activation or inhibition is determined by the signaling network context. Current therapies often 'train' cancer cells shifting them to a novel attractor, which has increased metastatic potential and drug resistance. The few therapy-surviving cancer cells are surrounded by massive cell death triggering a primordial adaptive and reparative general wound healing response. Overall, dynamic analysis of patient- and disease-stage specific intracellular and intercellular signaling networks may open new areas of anticancer therapy using multitarget drugs, drugs combinations, edgetic drugs, as well as help design 'gentler', differentiation and maintenance therapies. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Csermely, Peter] Semmelweis Univ, Dept Med Chem, POB 2, H-1428 Budapest, Hungary. [Korcsmaros, Tamas] Inst Food Res, Gut Hlth & Food Safety Programme, Norwich Res Pk, Norwich NR4 7UA, Norfolk, England. [Korcsmaros, Tamas] Genome Anal Ctr, Earlham Inst TGAC, Norwich Res Pk, Norwich NR4 7UH, Norfolk, England. [Nussinov, Ruth] 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 Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. RP Csermely, P (reprint author), Semmelweis Univ, Dept Med Chem, POB 2, H-1428 Budapest, Hungary. EM Csermely.Peter@med.semmelweis-univ.hu FU Frederick National Laboratory for Cancer Research, National Institutes of Health [HHSN261200800001E]; Biotechnology and Biological Sciences Research Council, UK; Hungarian National Research, Development and Innovation Office [K115378]; Intramural Research Program of NIH, Frederick National Lab, Center for Cancer Research FX The authors thank the authors of this special issue for their excellent and timely contributions. Work in the authors' laboratory was supported in part with Federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health, under contract HHSN261200800001E. TK is a Computational Biology Fellow at The Genome Analysis Centre in partnership with the Institute of Food Research (Norwich, UK), and strategically supported by Biotechnology and Biological Sciences Research Council, UK. Research in the lab of PC was supported by the Hungarian National Research, Development and Innovation Office (K115378). This research was supported in part by the Intramural Research Program of NIH, Frederick National Lab, 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 mention of trade names, commercial products ororganizations imply endorsement by the US Government. NR 69 TC 1 Z9 1 U1 11 U2 11 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD OCT PY 2016 VL 58 BP 55 EP 59 DI 10.1016/j.semcdb.2016.07.005 PG 5 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA DV9TD UT WOS:000383284000007 PM 27395026 ER PT J AU Nussinov, R Tsai, CJ Jang, H Korcsmaros, T Csermely, P AF Nussinov, Ruth Tsai, Chung-Jung Jang, Hyunbum Korcsmaros, Tamas Csermely, Peter TI Oncogenic KRAS signaling and YAP1/beta-catenin: Similar cell cycle control in tumor initiation SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Review DE K-Ras; Cancer; Hippo; Myc; WNT; Cellular pathways; Proliferation; Drug resistance ID BETA-CATENIN ACTIVATION; REGULATES C-MYC; RESTRICTION POINT; CANCER-THERAPIES; TARGETING RAS; PROTEIN INTERACTIONS; PANCREATIC-CANCER; K-RAS; PATHWAY; RESISTANCE AB Why are YAP1 and c-Myc often overexpressed (or activated) in KRAS-driven cancers and drug resistance? Here, we propose that there are two independent pathways in tumor proliferation: one includes MAPK/ERK and PI3K/A kt/mTOR; and the other consists of pathways leading to the expression ( or activation) of YAP1 and c-Myc. KRAS contributes through the first. MYC is regulated by e.g. beta-catenin, Notch and Hedgehog. We propose that YAP1 and ERK accomplish similar roles in cell cycle control, as do beta-catenin and PI3K. This point is compelling, since the question of how YAP1 rescues K-Ras or B-Raf ablation has recently captured much attention, as well as the mechanism of resistance to PI3K inhibitors. The similarity in cell cycle actions of beta-catenin and PI3K can also clarify the increased aggressiveness of lung cancer when both K-Ras and beta-catenin operate. Thus, we propose that the two pathways can substitute one another -or together amplify each other - in promoting proliferation. This new understanding of the independence and correspondence of the two pathways in cancer - MAPK/ERK and PI3K/Akt/mTOR; and YAP1 and c-Myc - provide a coherent and significant picture of signaling-driven oncogenic proliferation and may help in judicious, pathway-based drug discovery. (C) 2016 Ruth Nussinov. Published by Elsevier Ltd. All rights reserved. C1 [Nussinov, Ruth; Tsai, Chung-Jung; Jang, Hyunbum] 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 Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. [Korcsmaros, Tamas] Inst Food Res, Gut Hlth & Food Safety Programme, Norwich Res Pk, Norwich NR4 7UA, Norfolk, England. [Korcsmaros, Tamas] TGAC, Norwich Res Pk, Norwich NR4 7UA, Norfolk, England. [Korcsmaros, Tamas] Genome Anal Ctr, TGAC, Norwich Res Pk, Norwich NR4 7UH, Norfolk, England. [Csermely, Peter] Semmelweis Univ, Dept Med Chem, POB 2, H-1428 Budapest, Hungary. 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 Frederick National Laboratory for Cancer Research, National Institutes of Health [HHSN261200800001E]; Biotechnological and Biosciences Research Council, UK; Hungarian National Research, Development and Innovation Office [K115378]; Intramural Research Program of NIH, Frederick National Lab, Center for Cancer Research 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. TK is a Computational Biology Fellow at The Genome Analysis Centre in partnership with the Institute of Food Research (Norwich, UK), and strategically supported by Biotechnological and Biosciences Research Council, UK. Research in the lab of PC was supported by the Hungarian National Research, Development and Innovation Office (K115378). This research was supported [in part] by the Intramural Research Program of NIH, Frederick National Lab, 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 mention of trade names, commercial products or organizations imply endorsement by the US Government. NR 74 TC 5 Z9 5 U1 12 U2 12 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD OCT PY 2016 VL 58 BP 79 EP 85 DI 10.1016/j.semcdb.2016.04.001 PG 7 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA DV9TD UT WOS:000383284000010 PM 27058752 ER PT J AU Guven-Maiorova, E Tsai, CJ Nussinov, R AF Guven-Maiorova, Emine Tsai, Chung-Jung Nussinov, Ruth TI Pathogen mimicry of host protein-protein interfaces modulates immunity SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Review DE Molecular mimicry; Interface mimicry; Structure; Host-pathogen interactions; Protein-protein interactions; Multi-organism ID EPSTEIN-BARR-VIRUS; CONSTITUTIVE ACTIVATION; CRYSTAL-STRUCTURE; CONFORMATIONAL SELECTION; MOLECULAR MIMICRY; COUPLED-RECEPTOR; VIRAL CHEMOKINE; INDUCED FIT; TIR-DOMAIN; BACTERIAL AB Signaling pathways shape and transmit the cell's reaction to its changing environment; however, pathogens can circumvent this response by manipulating host signaling. To subvert host defense, they beat it at its own game: they hijack host pathways by mimicking the binding surfaces of host-encoded proteins. For this, it is not necessary to achieve global protein homology; imitating merely the interaction surface is sufficient. Different protein folds often interact via similar protein-protein interface architectures. This similarity in binding surfaces permits the pathogenic protein to compete with a host target protein. Thus, rather than binding a host-encoded partner, the host protein hub binds the pathogenic surrogate. The outcome can be dire: rewiring or repurposing the host pathways, shifting the cell signaling landscape and consequently the immune response. They can also cause persistent infections as well as cancer by modulating key signaling pathways, such as those involving Ras. Mapping the rewired host-pathogen 'superorganism' interaction network - along with its structural details - is critical for in-depth understanding of pathogenic mechanisms and developing efficient therapeutics. Here, we overview the role of molecular mimicry in pathogen host evasion as well as types of molecular mimicry mechanisms that emerged during evolution. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Guven-Maiorova, Emine; Tsai, Chung-Jung; Nussinov, Ruth] 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 emine.guven-maiorov@nih.gov; tsaic@mail.nih.gov; nussinor@helix.nih.gov OI Guven Maiorov, Emine/0000-0002-7388-9811 FU Federal funds from the 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 84 TC 0 Z9 0 U1 13 U2 13 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD OCT PY 2016 VL 58 BP 136 EP 145 DI 10.1016/j.semcdb.2016.06.004 PG 10 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA DV9TD UT WOS:000383284000016 PM 27287306 ER PT J AU Ahmed, MM Narendra, A Prasanna, P Coleman, CN Krishnan, S AF Ahmed, Mansoor M. Narendra, Amogh Prasanna, Pataje Coleman, C. Norman Krishnan, Sunil TI Current Insights in Radiation Combination Therapies: Influence of Omics and Novel Targeted Agents in Defining New Concepts in Radiation Biology and Clinical Radiation Oncology SO SEMINARS IN RADIATION ONCOLOGY LA English DT Editorial Material ID RADIOTHERAPY; EFFICACY C1 [Ahmed, Mansoor M.; Narendra, Amogh; Prasanna, Pataje; Coleman, C. Norman] NCI, Div Canc Treatment & Diag, Radiat Res Program, Bethesda, MA 20892 USA. [Krishnan, Sunil] Univ Texas Houston, Dept Radiat Oncol, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Krishnan, S (reprint author), Univ Texas Houston, Dept Radiat Oncol, MD Anderson Canc Ctr, Houston, TX 77030 USA.; Ahmed, MM (reprint author), NCI, Div Canc Treatment & Diag, Radiat Res Program, Rockville, MD 20850 USA. EM ahmedmm@mail.nih.gov; SKrishnan@mdanderson.org NR 21 TC 0 Z9 0 U1 2 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 1053-4296 EI 1532-9461 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD OCT PY 2016 VL 26 IS 4 BP 251 EP 253 DI 10.1016/j.semradonc.2016.07.002 PG 3 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DW4UY UT WOS:000383639700001 PM 27619246 ER PT J AU Makinde, AY Eke, I Aryankalayil, MJ Ahmed, MM Coleman, CN AF Makinde, Adeola Y. Eke, Iris Aryankalayil, Molykutty J. Ahmed, Mansoor M. Coleman, C. Norman TI Exploiting Gene Expression Kinetics in Conventional Radiotherapy, Hyperfractionation, and Hypofractionation for Targeted Therapy SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID NF-KAPPA-B; CANCER STEM-CELLS; FRACTIONATED RADIATION-THERAPY; EPITHELIAL-MESENCHYMAL TRANSITION; RANDOMIZED MULTICENTER TRIAL; RESIDUAL PANCREATIC-CANCER; PROSTATE-CANCER; BREAST-CANCER; LUNG-CANCER; ACCELERATED RADIOTHERAPY AB The dramatic changes in the technological delivery of radiation therapy, the repertoire of molecular targets for which pathway inhibitors are available, and the cellular and immunologic responses that can alter long-term clinical outcome provide a potentially unique role for using the radiation-inducible changes as therapeutic targets. Various mathematical models of dose and fractionation are extraordinarily useful in guiding treatment regimens. However, although the model may fit the clinical outcome, a deeper understanding of the molecular and cellular effect of the individual dose size and the adaptation to repeated exposure, called multifraction (MF) adaptation, may provide new therapeutic targets for use in combined modality treatments using radiochemotherapy and radioimmunotherapy. We discuss the potential of using different radiation doses and MF adaptation for targeting transcription factors, immune and inflammatory response, and cell "sternness." Given the complex genetic composition of tumors before treatment and their adaptation to drug treatment, innovative combinations using both the pretreatment molecular data and also the MF-adaptive response to radiation may provide an important role for focused radiation therapy as an integral part of precision medicine and immunotherapy. Published by Elsevier Inc. C1 [Makinde, Adeola Y.; Eke, Iris; Aryankalayil, Molykutty J.; Coleman, C. Norman] NCI, Radiat Oncol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. [Ahmed, Mansoor M.; Coleman, C. Norman] NCI, Radiat Res Program, NIH, Bethesda, MD 20892 USA. RP Makinde, AY (reprint author), NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,Bldg 10 Room B3B406, Bethesda, MD 20892 USA. EM adeola.makinde@nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 63 TC 2 Z9 2 U1 6 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-4296 EI 1532-9461 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD OCT PY 2016 VL 26 IS 4 BP 254 EP 260 DI 10.1016/j.semradonc.2016.07.001 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DW4UY UT WOS:000383639700002 PM 27619247 ER PT J AU Takebe, N Ahmed, MM Vikram, B Bernhard, EJ Zwiebel, J Coleman, CN Kunos, CA AF Takebe, Naoko Ahmed, Mansoor M. Vikram, Bhadrasain Bernhard, Eric J. Zwiebel, James Coleman, C. Norman Kunos, Charles A. TI Radiation-Therapeutic Agent Clinical Trials: Leveraging Advantages of a National Cancer Institute Programmatic Collaboration SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID RIBONUCLEOTIDE REDUCTASE INHIBITOR; 3-AMINOPYRIDINE-2-CARBOXALDEHYDE THIOSEMICARBAZONE 3-AP; SQUAMOUS-CELL CARCINOMA; HUMAN CERVICAL CANCERS; PHASE-I TRIAL; DNA-DAMAGE; POLY(ADP-RIBOSE) POLYMERASE; WEEKLY CISPLATIN; ONCOLOGY-GROUP; SOLID TUMORS AB A number of oncology phase II radiochemotherapy trials with promising results have been conducted late in the overall experimental therapeutic agent development process. Accelerated development and approval of experimental therapeutic agents have stimulated further interest in much earlier radiation-agent studies to increase the likelihood of success in phase III trials. To sustain this interest, more forward-thinking preclinical radiobiology experimental designs are needed to improve discovery of promising radiochemotherapy plus agent combinations for clinical trial testing. These experimental designs should better inform next step radiation-agent clinical trial dose, schedule, exposure, and therapeutic effect. Recognizing the need for a better strategy to develop preclinical data supporting radiation-agent phase I or II trials, the National Cancer Institute (NCI)-Cancer Therapy Evaluation Program (CTEP) and the NCI-Molecular Radiation Therapeutics Branch of the Radiation Research Program have partnered to promote earlier radiobiology studies of CTEP portfolio agents. In this Seminars in Radiation Oncology article, four key components of this effort are discussed. First, we outline steps for accessing CTEP agents for preclinical testing. Second, we propose radiobiology studies that facilitate transition from preclinical testing to early phase trial activation. Third, we navigate steps that walk through CTEP agent strategic development paths available for radiation-agent testing. Fourth, we highlight a new NCI-sponsored cooperative agreement grant supporting in vitro and in vivo radiation-CTEP agent testing that informs early phase trial designs. Throughout the article, we include contemporary examples of successful radiation agent development initiatives. Published by Elsevier Inc. C1 [Takebe, Naoko; Zwiebel, James; Kunos, Charles A.] NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. [Ahmed, Mansoor M.; Vikram, Bhadrasain; Bernhard, Eric J.; Coleman, C. Norman] NCI, Radiat Res Program, Bethesda, MD 20892 USA. RP Takebe, N (reprint author), NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. NR 60 TC 2 Z9 2 U1 5 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-4296 EI 1532-9461 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD OCT PY 2016 VL 26 IS 4 BP 271 EP 280 DI 10.1016/j.semradonc.2016.06.005 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DW4UY UT WOS:000383639700004 PM 27619249 ER PT J AU Ford, E Deye, J AF Ford, Eric Deye, Jim TI Current Instrumentation and Technologies in Modern Radiobiology Research-Opportunities and Challenges SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID RADIATION RESEARCH PLATFORM; SMALL ANIMAL IRRADIATOR; STEREOTACTIC BODY RADIOTHERAPY; INDUCED LUNG INJURY; X-RAY; GOLD NANOPARTICLES; CANCER-RESEARCH; DOSIMETRY STANDARDIZATION; SYNCHROTRON MICROBEAM; CONFORMAL IRRADIATOR AB There is a growing awareness of the gaps in the technical methods employed in radiation biology experiments. These quality gaps can have a substantial effect on the reliability and reproducibility of results as outlined in several recent meta-studies. This is especially true in the context of the newer laboratory irradiation technologies. These technologies allow for delivery of highly localized dose distributions and increased spatial accuracy but also present increased challenges of their own. In this article, we highlight some of the features of the new technologies and the experiments they support; this includes image-guided localized radiation systems, microirradiator systems using carbon nanotubes and physical radiation modifiers like gold nanoparticles. We discuss the key technical issues related to the consistency and quality of modern radiation biology experiments including dosimetry protocols that are essential to all experiments, quality assurance approaches, methods to validate physical radiation targeting including immunohistochemical assays and other biovalidation apprpaches. We highlight the future needs in terms of education and training and the creation of tools for cross-institutional benchmarking quality in preclinical studies. The demands for increased experimental rigor are challenging but can be met with an awareness and a systematic approach which ensures quality. (C) 2016 Published by Elsevier Inc. C1 [Ford, Eric] Univ Washington, Med Ctr, Dept Radiat Oncol, Seattle, WA 98195 USA. [Deye, Jim] NCI, Radiat Res Program, Bethesda, MD 20892 USA. RP Ford, E (reprint author), Dept Radiat Oncol, Gox 356043,1959 NE Pacific St, Seattle, WA 98195 USA. EM eford@uw.edu NR 83 TC 2 Z9 2 U1 10 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-4296 EI 1532-9461 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD OCT PY 2016 VL 26 IS 4 BP 349 EP 355 DI 10.1016/j.semradonc.2016.06.002 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DW4UY UT WOS:000383639700011 PM 27619256 ER PT J AU Mukherjee, S Sirohi, D Dowd, KA Chen, ZG Diamond, MS Kuhn, RJ Pierson, TC AF Mukherjee, Swati Sirohi, Devika Dowd, Kimberly A. Chen, Zhenguo Diamond, Michael S. Kuhn, Richard J. Pierson, Theodore C. TI Enhancing dengue virus maturation using a stable furin over-expressing cell line SO VIROLOGY LA English DT Article DE Flavivirus; Dengue virus; West Nile virus; Virion maturation; Antibody neutralization; Furin ID WEST-NILE-VIRUS; BORNE ENCEPHALITIS-VIRUS; ANTIBODY-MEDIATED NEUTRALIZATION; ENDOPLASMIC-RETICULUM; MONOCLONAL-ANTIBODY; ENVELOPE PROTEIN; STRUCTURAL BASIS; FLAVIVIRUSES; INFECTION; PRM AB Flaviviruses are positive-stranded RNA viruses that incorporate envelope (E) and premembrane (prM) proteins into the virion. Furin-mediated cleavage of prM defines a required maturation step in the flavivirus lifecycle. Inefficient prM cleavage results in structurally heterogeneous virions with unique antigenic and functional characteristics. Recent studies with dengue virus suggest that viruses produced in tissue culture cells are less mature than those produced in primary cells. In this study, we describe a Vero cell line that ectopically expresses high levels of human furin (Vero-furin) for use in the production of more homogenous mature flavivirus populations. Laboratory-adapted and clinical dengue virus isolates grow efficiently in Vero-furin cells. Biochemical and structural techniques demonstrate efficient prM cleavage in Vero-furin derived virus preparations. These virions also were less sensitive to neutralization by antibodies that bind efficiently to immature virions. This furin-expressing cell line will be of considerable utility for flavivirus neutralization and structural studies. Published by Elsevier Inc. C1 [Mukherjee, Swati; Dowd, Kimberly A.; Pierson, Theodore C.] NIAID, Viral Pathogenesis Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Sirohi, Devika; Chen, Zhenguo; Kuhn, Richard J.] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA. [Sirohi, Devika; Chen, Zhenguo; Kuhn, Richard J.] Purdue Univ, Purdue Inst Inflammat Immunol & Infect Dis, W Lafayette, IN 47907 USA. [Diamond, Michael S.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Diamond, Michael S.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. [Diamond, Michael S.] Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA. [Diamond, Michael S.] Washington Univ, Sch Med, Dept Immunol, St Louis, MO 63110 USA. [Diamond, Michael S.] Washington Univ, Sch Med, Ctr Human Immunol & Immunotherapy Programs, St Louis, MO 63110 USA. RP Pierson, TC (reprint author), NIH, Viral Pathogenesis Sect, Viral Dis Lab, Bldg 33,Room 2E19A-2, Bethesda, MD 20892 USA. EM piersontc@mail.nih.gov FU intramural program of the National Institute of Allergy and Infectious Diseases; National Institutes of Health [R01AI073755] FX This work was supported in part by the intramural program of the National Institute of Allergy and Infectious Diseases and National Institutes of Health (TCP) an extramural grant under award numbers R01AI073755 (MSD and RJK). We are grateful to Heather Hickman for her constructive comments on the manuscript. Finally, the authors are grateful to members of their laboratories for helpful discussions. NR 50 TC 2 Z9 2 U1 7 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD OCT PY 2016 VL 497 BP 33 EP 40 DI 10.1016/j.virol.2016.06.022 PG 8 WC Virology SC Virology GA DW8RC UT WOS:000383922200004 PM 27420797 ER PT J AU Liu, QP Yan, YH Kozak, CA AF Liu, Qingping Yan, Yuhe Kozak, Christine A. TI Permissive XPR1 gammaretrovirus receptors in four mammalian species are functionally distinct in interference tests SO VIROLOGY LA English DT Article DE Mouse gammaretroviruses; Mouse leukemia viruses; XPR1 retrovirus receptor; Gammaretrovirus interference ID MURINE LEUKEMIA VIRUSES; CELL-SURFACE RECEPTOR; MOUSE XENOTROPIC GAMMARETROVIRUSES; WILD MICE; RETROVIRUS XMRV; HOST-RANGE; INFECTION; DETERMINANTS; GLYCOPROTEIN; VARIANTS AB Xenotropic/polytropic mouse leukemia viruses (X/P-MLVs) use the XPR1 gammaretrovirus receptor for entry. X/P-MLV host range is defined by usage of naturally occurring restrictive XPR1 receptors, and is governed by polymorphisms in the virus envelope glycoprotein and in XPR1. Here, we examined receptors of four mammalian species permissive to all X/P-MLVs (Mus dunni, human, rabbit, mink). Interference assays showed the four to be functionally distinct. Preinfection with X-MLVs consistently blocked all nine XPR1-dependent viruses, while preinfection with P-MLVs and wild mouse X/P-MLVs produced distinctive interference patterns in the four cells. These patterns indicate shared usage of independent, but not always fully functional, receptor sites. XPR1 sequence comparisons identified candidate sites in receptor-determining regions that correlate with some interference patterns. The evolutionary record suggests that the X/P-MLV tropism variants evolved to adapt to host receptor polymorphisms, to circumvent blocks by competing viruses or to avoid host-encoded envelope glycoproteins acquired for defense. Published by Elsevier Inc. C1 [Liu, Qingping; Yan, Yuhe; Kozak, Christine A.] NIAID, Mol Microbiol Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Yan, Yuhe] Yisheng US Biopharma Inc, Gaithersburg, MD USA. RP Kozak, CA (reprint author), NIAID, Mol Microbiol Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ckozak@niaid.nih.gov FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases, Bethesda, MD FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, Bethesda, MD. We thank Venkat Yedavalli for assistance with figure preparation. NR 49 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD OCT PY 2016 VL 497 BP 53 EP 58 DI 10.1016/j.virol.2016.06.026 PG 6 WC Virology SC Virology GA DW8RC UT WOS:000383922200006 PM 27423269 ER PT J AU Blumberg, SJ Zablotsky, B Avila, RM Colpe, LJ Pringle, BA Kogan, MD AF Blumberg, Stephen J. Zablotsky, Benjamin Avila, Rosa M. Colpe, Lisa J. Pringle, Beverly A. Kogan, Michael D. TI Diagnosis lost: Differences between children who had and who currently have an autism spectrum disorder diagnosis SO AUTISM LA English DT Article DE autism spectrum disorder; diagnosis; epidemiology; national surveys ID DOUBLY ROBUST ESTIMATION; CAUSAL INFERENCE; FOLLOW-UP; STABILITY; HISTORY; IDENTIFICATION; INTERVENTION; ADOLESCENTS; PREVALENCE; SYMPTOMS AB Autism spectrum disorder diagnoses sometimes change due to misdiagnosis, maturation, or treatment. This study uses a probability-based national surveythe Survey of Pathways to Diagnosis and Servicesto compare currently diagnosed (n=1420) and previously diagnosed (n=187) children aged 6-17years based on retrospective parental reports of early concerns about their children's development, responses to those concerns by doctors and other healthcare providers, the type of provider who made the first autism spectrum disorder diagnosis, and the autism spectrum disorder subtype diagnoses received (if any). Propensity score matching was used to control for differences between the groups on children's current level of functioning and other current characteristics that may have been related to diagnosis loss. Approximately 13% of the children ever diagnosed with autism spectrum disorder were estimated to have lost the diagnosis, and parents of 74% of them believed it was changed due to new information. Previously diagnosed children were less likely to have parents with early concerns about verbal skills, nonverbal communication, learning, and unusual gestures or movements. They were also less likely to have been referred to and diagnosed by a specialist. Previously diagnosed children were less likely to have ever received a diagnosis of Asperger's disorder or autistic disorder. C1 [Blumberg, Stephen J.; Zablotsky, Benjamin] Ctr Dis Control & Prevent, Hyattsville, MD USA. [Avila, Rosa M.] Univ Washington, Seattle, WA 98195 USA. [Colpe, Lisa J.; Pringle, Beverly A.] NIH, Bldg 10, Bethesda, MD 20892 USA. [Kogan, Michael D.] Hlth Resources & Serv Adm, Rockville, MD USA. RP Blumberg, SJ (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, 3311 Toledo Rd, Hyattsville, MD 20782 USA. EM sblumberg@cdc.gov FU Intramural CDC HHS [CC999999] NR 49 TC 0 Z9 0 U1 18 U2 18 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1362-3613 EI 1461-7005 J9 AUTISM JI Autism PD OCT PY 2016 VL 20 IS 7 BP 783 EP 795 DI 10.1177/1362361315607724 PG 13 WC Psychology, Developmental SC Psychology GA DV5JQ UT WOS:000382963700002 PM 26489772 ER PT J AU Watson, DC Bayik, D Srivatsan, A Bergamaschi, C Valentin, A Niu, G Bear, J Monninger, M Sun, M Morales-Kastresana, A Jones, JC Felber, BK Chen, XY Gursel, I Pavlakis, GN AF Watson, Dionysios C. Bayik, Defne Srivatsan, Avinash Bergamaschi, Cristina Valentin, Antonio Niu, Gang Bear, Jenifer Monninger, Mitchell Sun, Mei Morales-Kastresana, Aizea Jones, Jennifer C. Felber, Barbara K. Chen, Xiaoyuan Gursel, Ihsan Pavlakis, George N. TI Efficient production and enhanced tumor delivery of engineered extracellular vesicles SO BIOMATERIALS LA English DT Article DE Exosomes; Drug delivery; Biodistribution; Scavenger receptor; Reticuloendothelial system; Dextran sulfate ID CELL-DERIVED EXOSOMES; SCAVENGER RECEPTOR; IN-VIVO; B16BL6-DERIVED EXOSOMES; CLASS-A; IL-15; MICE; BIODISTRIBUTION; IL-15R-ALPHA; CANCER AB Extracellular vesicles (EV), including exosomes and microvesicles, are nano-sized intercellular communication vehicles that participate in a multitude of physiological processes. Due to their biological properties, they are also promising candidates for the systemic delivery of therapeutic compounds, such as cytokines, chemotherapeutic drugs, siRNAs and viral vectors. However, low EV production yield and rapid clearance of administered EV by liver macrophages limit their potential use as therapeutic vehicles. We have used a hollow-fiber bioreactor for the efficient production of bioactive EV bearing the heterodimeric cytokine complex Interleukin-15:Interleukin-15 receptor alpha. Bioreactor culture yielded-40fold more EV per mL conditioned medium, as compared to conventional cell culture. Biophysical analysis and comparative proteomics suggested a more diverse population of EV in the bioreactor preparations, while serum protein contaminants were detectable only in conventional culture EV preparations. We also identified the Scavenger Receptor Class A family (SR-A) as a novel monocyte/macrophage uptake receptor for EV. In vivo blockade of SR-A with dextran sulfate dramatically decreased EV liver clearance in mice, while enhancing tumor accumulation. These findings facilitate development of EV therapeutic methods. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). C1 [Watson, Dionysios C.; Valentin, Antonio; Pavlakis, George N.] Natl Canc Inst Frederick, Ctr Canc Res, Vaccine Branch, Human Retrovirus Sect, Frederick, MD 21702 USA. [Bayik, Defne] Natl Canc Inst Frederick, Ctr Canc Res, Canc & Inflammat Program, Frederick, MD 21702 USA. [Bayik, Defne; Gursel, Ihsan] Bilkent Univ, Dept Mol Biol & Genet, TR-06800 Ankara, Turkey. [Srivatsan, Avinash; Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. [Bergamaschi, Cristina; Bear, Jenifer; Felber, Barbara K.] Natl Canc Inst Frederick, Ctr Canc Res, Vaccine Branch, Human Retrovirus Pathogenesis Sect, Frederick, MD 21702 USA. [Monninger, Mitchell; Sun, Mei] United States Army, Div Pathol, Med Res Inst Infect Dis, Frederick, MD 21702 USA. [Morales-Kastresana, Aizea; Jones, Jennifer C.] NCI, Vaccine Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Pavlakis, GN (reprint author), Natl Canc Inst Frederick, Ctr Canc Res, Vaccine Branch, Human Retrovirus Sect, Frederick, MD 21702 USA. EM George.pavlakis@nih.gov RI Jones, Jennifer/C-8691-2015; OI Jones, Jennifer/0000-0002-9488-7719; Watson, Dionysios/0000-0002-9146-5641 FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research; Admune/Novartis; National Cancer Institute/NIH, USA FX We thank William C. Kopp and Yanyt Wang for the IL-15 bioactivity testing; Ming Zhou for mass spectrometry; John Cad well for discussions and for providing Fibercell hollow-fiber materials; Joseph Meyer for artwork; and Terry Jones for administrative support. Research supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. Research also supported by Admune/Novartis through a collaborative agreement with the National Cancer Institute/NIH, USA. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the U.S. Army. NR 40 TC 4 Z9 4 U1 46 U2 48 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 EI 1878-5905 J9 BIOMATERIALS JI Biomaterials PD OCT PY 2016 VL 105 BP 195 EP 205 DI 10.1016/j.biomaterials.2016.07.003 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA DV9ZD UT WOS:000383299800018 PM 27522254 ER PT J AU Burgess, AP Fouquet, NC Seri, S Hawken, MB Heard, A Neasham, D Little, MP Elliott, P AF Burgess, Adrian P. Fouquet, Nathalie C. Seri, Stefano Hawken, Malcolm B. Heard, Andrew Neasham, David Little, Mark P. Elliott, Paul TI Acute Exposure to Terrestrial Trunked Radio (TETRA) has effects on the electroencephalogram and electrocardiogram, consistent with vagal nerve stimulation SO ENVIRONMENTAL RESEARCH LA English DT Article DE Electromagnetic fields; Exposure; Neurophysiological effects; Occupational cohort; Radio frequency ID HEART-RATE-VARIABILITY; ELF MAGNETIC-FIELD; VAGUS NERVE; ELECTROMAGNETIC-FIELDS; RESTING EEG; SLEEP EEG; BLOOD-PRESSURE; MOBILE PHONES; HUMANS; POTENTIALS AB Background: Terrestrial Trunked Radio (TETRA) is a telecommunications system widely used by police and emergency services around the world. The Stewart Report on mobile telephony and health raised questions about possible health effects associated with TETRA signals. This study investigates possible effects of TETRA signals on the electroencephalogram and electrocardiogram in human volunteers. Methods: Blinded randomized provocation study with a standardized TETRA signal or sham exposure. In the first of two experiments, police officers had a TETRA set placed first against the left temple and then the upper-left quadrant of the chest and the electroencephalogram was recorded during rest and active cognitive processing. In the second experiment, volunteers were subject to chest exposure of TETRA whilst their electroencephalogram and heart rate variability derived from the electrocardiogram were recorded. Results: In the first experiment, we found that exposure to TETRA had consistent neurophysiological effects on the electroencephalogram, but only during chest exposure, in a pattern suggestive of vagal nerve stimulation. In the second experiment, we observed changes in heart rate variability during exposure to TETRA but the electroencephalogram effects were not replicated. Conclusions: Observed effects of exposure to TETRA signals on the electroencephalogram (first experiment) and electrocardiogram are consistent with vagal nerve stimulation in the chest by TETRA. However given the small effect on heart rate variability and the lack of consistency on the electroencephalogram, it seems unlikely that this will have a significant impact on health. Long-term monitoring of the health of the police force in relation to TETRA use is on-going. (C) 2016 The Authors. Published by Elsevier Inc. C1 [Burgess, Adrian P.; Fouquet, Nathalie C.; Seri, Stefano] Aston Univ, Sch Life & Hlth Sci, Aston Brain Ctr, Birmingham B4 7ET, W Midlands, England. [Hawken, Malcolm B.] Liverpool John Moores Univ, Res Inst Sport & Exercise Sci, Reilly Bldg,Byrom St, Liverpool L3 3AF, Merseyside, England. [Heard, Andrew; Elliott, Paul] Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, St Marys Campus, London W2 1PG, England. [Neasham, David] Creativ Ceut Ltd, Bank Chambers,10 Borough High St, London SE1 9QQ, England. [Little, Mark P.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Burgess, AP (reprint author), Aston Univ, Sch Life & Hlth Sci, Aston Brain Ctr, Birmingham B4 7ET, W Midlands, England.; Elliott, P (reprint author), Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, St Marys Campus, London W2 1PG, England. EM a.p.burgess@aston.ac.uk; p.elliott@imperial.ac.uk OI Burgess, Adrian P/0000-0002-0977-8105 FU UK Home Office [780-TETRA]; UK Department of Health Policy Research Programme [RDD/091/210]; National Institute for Health Research (NIHR) Biomedical Research Centre at Imperial College Healthcare NHS Trust and Imperial College London; Medical Research Council - Public Health England (MRC-PHE) Centre for Environment and Health; NIHR Health Protection Research Unit on Health Impact of Environmental Hazards FX This work was supported by the UK Home Office [780-TETRA; Experiment 1] and the UK Department of Health Policy Research Programme [RDD/091/210; Experiment 2]. P.E. is an NIHR senior investigator and is supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at Imperial College Healthcare NHS Trust and Imperial College London, the Medical Research Council - Public Health England (MRC-PHE) Centre for Environment and Health and the NIHR Health Protection Research Unit on Health Impact of Environmental Hazards.. The views expressed in this publication are those of the authors and not necessarily those of the Home Office, the Department of Health or the NIHR. NR 56 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 EI 1096-0953 J9 ENVIRON RES JI Environ. Res. PD OCT PY 2016 VL 150 BP 461 EP 469 DI 10.1016/j.envres.2016.06.031 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA DV4NU UT WOS:000382903100056 PM 27419367 ER PT J AU Persky, S Ferrer, RA Klein, WMP AF Persky, Susan Ferrer, Rebecca A. Klein, William M. P. TI Nonverbal and paraverbal behavior in (simulated) medical visits related to genomics and weight: a role for emotion and race SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE Nonverbal behavior; Paraverbal behavior; Physician-patient interaction; Genomics; Emotion; Obesity; Race ID IMMERSIVE VIRTUAL ENVIRONMENT; HEALTH-CARE; CANCER-RISK; FAT PEOPLE; COMMUNICATION; PREJUDICE; OUTCOMES; METAANALYSIS; ASSOCIATION; INFORMATION AB It is crucial to examine patient reactions to genomics-informed approaches to weight management within a clinical context, and understand the influence of patient characteristics (here, emotion and race). Examining nonverbal reactions offers a window into patients' implicit cognitive, attitudinal and affective processes related to clinical encounters. We simulated a weight management clinical interaction with a virtual reality-based physician, and experimentally manipulated patient emotional state (anger/fear) and whether the physician made genomic or personal behavior attributions for weight. Participants were 190 overweight females who racially identified as either Black or White. Participants made less visual contact when receiving genomic information in the anger condition, and Black participants exhibited lowered voice pitch when receiving genomic information. Black participants also increased their interpersonal distance when receiving genomic information in the anger condition. By studying non-conscious nonverbal behavior, we can better understand the nuances of these interactions. Trial registry clinicaltrials.gov NCT01888913. C1 [Persky, Susan] NHGRI, Social & Behav Res Branch, Bldg 31,Rm B1B36,31 Ctr Dr,MSC 2073, Bethesda, MD 20892 USA. [Ferrer, Rebecca A.] NCI, Basic Biobehav & Psychol Sci Branch, Behav Res Program, Bethesda, MD 20892 USA. [Klein, William M. P.] NCI, Behav Res Program, Bethesda, MD 20892 USA. RP Persky, S (reprint author), NHGRI, Social & Behav Res Branch, Bldg 31,Rm B1B36,31 Ctr Dr,MSC 2073, Bethesda, MD 20892 USA. EM perskys@mail.nih.gov FU Intramural Research Program of the National Human Genome Research Institute FX This study was funded by the Intramural Research Program of the National Human Genome Research Institute. NR 51 TC 0 Z9 0 U1 10 U2 10 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0160-7715 EI 1573-3521 J9 J BEHAV MED JI J. Behav. Med. PD OCT PY 2016 VL 39 IS 5 BP 804 EP 814 DI 10.1007/s10865-016-9747-5 PG 11 WC Psychology, Clinical SC Psychology GA DV4HS UT WOS:000382887100006 PM 27146511 ER EF