FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Abhishek, F
Heist, E
Elmariah, S
Passeri, J
Palacios, I
Inglessis, I
Baker, J
Vlahakes, G
Ruskin, J
Mansour, M
AF Abhishek, Fnu
Heist, Edwin
Elmariah, Sammy
Passeri, Jonathan
Palacios, Igor
Inglessis, Ignacio
Baker, Joshua
Vlahakes, Gus
Ruskin, Jeremy
Mansour, Moussa
TI CLINICAL IMPACT OF PERSISTENT LEFT BUNDLE BRANCH BLOCK AND PERMANENT
PACEMAKER IMPLANTATION AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT ON
LEFT VENTICULAR FUNCTION
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
NR 0
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 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1123-352
BP A1958
EP A1958
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579102716
ER
PT J
AU Arora, P
Reingold, J
Baggish, A
Guanaga, D
Wu, C
Ghorbani, A
Chen-Tournoux, A
Khan, A
Tainsh, L
Buys, E
Williams, J
Scherrer-Crosbie, M
Newton-Cheh, C
Kaplan, L
Wang, T
AF Arora, Pankaj
Reingold, Jason
Baggish, Aaron
Guanaga, Derek
Wu, Connie
Ghorbani, Anahita
Chen-Tournoux, Annabel
Khan, Abigail
Tainsh, Laurel
Buys, Emmanuel
Williams, Jonathan
Scherrer-Crosbie, Marielle
Newton-Cheh, Christopher
Kaplan, Lee
Wang, Thomas
TI WEIGHT LOSS, SALINE LOADING, AND THE NATRIURETIC PEPTIDE SYSTEM
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Univ Alabama Birmingham, Birmingham, AL USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1144-144
BP A1354
EP A1354
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579102112
ER
PT J
AU Bertrand, PB
Verhaert, D
Smeets, CJ
Verbrugge, FH
Grieten, L
Mullens, W
Gutermann, H
Dion, RA
Levine, R
Vandervoort, PM
AF Bertrand, Philippe B.
Verhaert, David
Smeets, Christophe J.
Verbrugge, Frederik H.
Grieten, Lars
Mullens, Wilfried
Gutermann, Herbert
Dion, Robert A.
Levine, Robert
Vandervoort, Pieter M.
TI EXERCISE-INDUCED INCREASE IN EFFECTIVE MITRAL VALVE AREA AFTER
RESTRICTIVE MITRAL VALVE ANNULOPLASTY
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Hosp Oost Limburg, Genk, Belgium.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
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 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1243M-366B
BP A1929
EP A1929
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579102687
ER
PT J
AU Bui, A
Cannon, C
Steg, P
Storey, R
Husted, S
Ren, F
James, S
Michelson, E
Himmelmann, A
Wallentin, L
Scirica, B
AF Bui, An
Cannon, Christopher
Steg, Philippe
Storey, Robert
Husted, Steen
Ren, Fang
James, Stefan
Michelson, Eric
Himmelmann, Anders
Wallentin, Lars
Scirica, Benjamin
TI RISK OF CARDIOVASCULAR DEATH AND NON-SUSTAINED VENTRICULAR TACHYCARDIA
DETECTED 30-DAYS AFTER ACUTE CORONARY SYNDROME IN THE PLATO (PLATELET
INHIBITION AND PATIENT OUTCOMES) TRIAL
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 TIMI Study Grp, Boston, MA USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 921-06
BP A298
EP A298
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579100299
ER
PT J
AU Chatterjee, N
Singh, J
Szymonifka, J
Lavender, Z
Smith, C
Januzzi, J
Truong, Q
AF Chatterjee, Neal
Singh, Jagmeet
Szymonifka, Jackie
Lavender, Zachary
Smith, Chelsea
Januzzi, James
Quynh Truong
TI INCREMENTAL VALUE OF CYSTATIN C BEYOND CONVENTIONAL MARKERS OF RENAL
FUNCTION FOR PREDICTING CLINICAL RESPONSE IN PATIENTS RECEIVING CARDIAC
RESYNCHRONIZATION THERAPY: THE BIOCRT STUDY
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 [Chatterjee, Neal; Singh, Jagmeet; Szymonifka, Jackie; Lavender, Zachary; Smith, Chelsea; Januzzi, James; Quynh Truong] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1221-203
BP A916
EP A916
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579101574
ER
PT J
AU Cheezum, M
Subramaniyam, PS
Bittencourt, M
Hulten, E
Ghoshhajra, B
Shah, N
Forman, D
Hainer, J
Leavitt, M
Padmanabhan, R
Skali, H
Dorbala, S
Hoffmann, U
Abbara, S
Gewirtz, H
Di Carli, M
Blankstein, R
AF Cheezum, Michael
Subramaniyam, Prem Srinivas
Bittencourt, Marcio
Hulten, Edward
Ghoshhajra, Brian
Shah, Nishant
Forman, Daniel
Hainer, Jon
Leavitt, Marcia
Padmanabhan, Ram
Skali, Hicham
Dorbala, Sharmila
Hoffmann, Udo
Abbara, Suhny
Gewirtz, Henry
Di Carli, Marcelo
Blankstein, Ron
TI PROGNOSTIC VALUE OF CORONARY CTA VERSUS EXERCISE TREADMILL TESTING
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1239M-362B
BP A983
EP A983
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579101641
ER
PT J
AU Elmariah, S
Inglessis, I
Baker, J
Stewart, W
Lindman, B
Xu, K
Alu, M
Vlahakes, G
Kodali, S
Dal-Bianco, J
Melnitchouk, S
Leon, M
Svensson, L
Pibarot, P
Douglas, P
Weissman, N
Hahn, R
Palacios, I
Passeri, J
AF Elmariah, Sammy
Inglessis, Ignacio
Baker, Joshua
Stewart, William
Lindman, Brian
Xu, Ke
Alu, Maria
Vlahakes, Gus
Kodali, Susheel
Dal-Bianco, Jacob
Melnitchouk, Serguei
Leon, Martin
Svensson, Lars
Pibarot, Philippe
Douglas, Pamela
Weissman, Neil
Hahn, Rebecca
Palacios, Igor
Passeri, Jonathan
TI PATTERNS OF LEFT VENTRICULAR REMODELING IN PATIENTS WITH SEVERE AORTIC
STENOSIS IN THE PARTNER TRIAL
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 [Elmariah, Sammy; Inglessis, Ignacio; Baker, Joshua; Stewart, William; Lindman, Brian; Xu, Ke; Alu, Maria; Vlahakes, Gus; Kodali, Susheel; Dal-Bianco, Jacob; Melnitchouk, Serguei; Leon, Martin; Svensson, Lars; Pibarot, Philippe; Douglas, Pamela; Weissman, Neil; Hahn, Rebecca; Palacios, Igor; Passeri, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 919-07
BP A1937
EP A1937
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579102695
ER
PT J
AU Emami, H
Singh, P
MacNabb, M
Figueroa, A
Abdelbaky, A
Nasir, K
Hoffmann, U
Nahrendorf, M
Tawakol, A
AF Emami, Hamed
Singh, Parmanand
MacNabb, Megan
Figueroa, Amparo
Abdelbaky, Amr
Nasir, Khurram
Hoffmann, Udo
Nahrendorf, Matthias
Tawakol, Ahmed
TI INCREASED BONE MARROW METABOLIC ACTIVITY IS ASSOCIATED WITH INCREASED
RISK OF FUTURE CARDIOVASCULAR EVENTS
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Baptist Hlth Med Grp, Miami Beach, FL USA.
NR 0
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 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1165M-362A
BP A976
EP A976
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579101634
ER
PT J
AU Ferencik, M
Puchner, S
Liu, T
Mayrhofer, T
Truong, Q
Lee, H
Fleg, J
Nagurney, J
Udelson, J
Hoffmann, U
AF Ferencik, Maros
Puchner, Stefan
Liu, Ting
Mayrhofer, Thomas
Truong, Quynh
Lee, Hang
Fleg, Jerome
Nagurney, John
Udelson, James
Hoffmann, Udo
TI HIGH-RISK PLAQUE PREDICTS ACUTE CORONARY SYNDROME INDEPENDENTLY OF
SIGNIFICANT CAD IN PATIENTS WITH ACUTE CHEST PAIN: RESULTS FROM ROMICAT
II
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 914-07
BP A1003
EP A1003
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579101661
ER
PT J
AU Gandhi, PU
Motiwala, S
Sheftel, AD
Weiner, R
Baggish, A
Gaggin, H
Liu, P
Januzzi, J
AF Gandhi, Parul U.
Motiwala, Shweta
Sheftel, Alex D.
Weiner, Rory
Baggish, Aaron
Gaggin, Hanna
Liu, Peter
Januzzi, James
TI INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN 7 IN HEART FAILURE PATIENTS:
A NOVEL BIOMARKER OF MYOCARDIAL DIASTOLIC FUNCTION?
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Univ Ottawa, Inst Heart, Ottawa, ON, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1114-192
BP A788
EP A788
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579101446
ER
PT J
AU Hariharan, P
Dudzinski, D
Okechukwu, I
Takayesu, J
Chang, YC
Kabrhel, C
AF Hariharan, Praveen
Dudzinski, David
Okechukwu, Ikenna
Takayesu, James
Chang, Yuchiao
Kabrhel, Christopher
TI ASSOCIATION BETWEEN ELECTROCARDIOGRAPHIC FINDINGS, RIGHT HEART STRAIN
AND SHORT-TERM ADVERSE CLINICAL EVENTS IN PATIENTS WITH ACUTE PULMONARY
EMBOLISM
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 [Hariharan, Praveen; Dudzinski, David; Okechukwu, Ikenna; Takayesu, James; Chang, Yuchiao; Kabrhel, Christopher] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1188-213
BP A1492
EP A1492
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579102250
ER
PT J
AU Jia, HB
Dauerman, H
Toma, C
Samady, H
Lee, S
Vergallo, R
Hu, SN
Tian, JW
Soeda, T
Wang, Z
Lee, H
McNulty, I
Yu, B
Uemura, S
Jang, IK
AF Jia, Haibo
Dauerman, Harold
Toma, Catalin
Samady, Habib
Lee, Stephen
Vergallo, Rocco
Hu, Sining
Tian, Jinwei
Soeda, Tsunenari
Wang, Zhao
Lee, Hang
McNulty, Iris
Yu, Bo
Uemura, Shiro
Jang, Ik-Kyung
TI MANAGEMENT AND CLINICAL OUTCOME OF PATIENTS WITH ACUTE CORONARY SYNDROME
CAUSED BY PLAQUE RUPTURE AND PLAQUE EROSION: AN INTRAVASCULAR OPTICAL
COHERENCE TOMOGRAPHY STUDY
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Harbin, Peoples R China.
NR 0
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 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1117-250
BP A72
EP A72
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579100073
ER
PT J
AU Kataoka, A
Zeng, X
Garcia, M
Seybolt, M
Sullivan, S
Guerrero, J
Muriuki, M
Kozak, A
Braithwaite, G
Handschumacher, M
Levine, R
Hung, J
AF Kataoka, Akihisa
Zeng, Xin
Garcia, Michael
Seybolt, Margo
Sullivan, Suzanne
Guerrero, Jose
Muriuki, Maryanne
Kozak, Adam
Braithwaite, Gavin
Handschumacher, Mark
Levine, Robert
Hung, Judy
TI DEVELOPMENT AND APPLICATION OF POLYMER-MATRIX DEVICE TO REMODEL LEFT
VENTRICULAR - MITRAL VALVE APPARATUS IN ISCHEMIC MITRAL REGURGITATION
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Kataoka, Akihisa; Zeng, Xin; Garcia, Michael; Seybolt, Margo; Sullivan, Suzanne; Guerrero, Jose; Muriuki, Maryanne; Kozak, Adam; Braithwaite, Gavin; Handschumacher, Mark; Levine, Robert; Hung, Judy] Cambridge Polymer Grp Inc, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1196-353
BP A1993
EP A1993
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579102751
ER
PT J
AU Kato, ET
Bonaca, M
Morrow, D
Jarolim, P
Sloan, S
Solomon, S
Braunwald, E
Sabatine, M
AF Kato, Eri Toda
Bonaca, Marc
Morrow, David
Jarolim, Petr
Sloan, Sarah
Solomon, Scott
Braunwald, Eugene
Sabatine, Marc
TI GROWTH DIFFERENTIATION FACTOR-15 (GDF-15) AND THE RISK OF CARDIOVASCULAR
EVENTS IN PATIENTS WITH STABLE ISCHEMIC HEART DISEASE
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 TIMI Study Grp, Boston, MA USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 908-06
BP A1525
EP A1525
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579102283
ER
PT J
AU Kim, J
Al Mheid, I
Malekzadegan, M
Sher, S
Shoop, J
Galante, A
Williams, B
Sperling, L
Weiner, R
Baggish, A
Quyyumi, A
AF Kim, Jonathan
Al Mheid, Ibhar
Malekzadegan, Mohammad
Sher, Salman
Shoop, Jay
Galante, Angelo
Williams, Byron
Sperling, Laurence
Weiner, Rory
Baggish, Aaron
Quyyumi, Arshed
TI ARTERIAL STIFFNESS IN NATIONAL COLLEGIATE ATHLETIC ASSOCIATION DIVISION
I AMERICAN-STYLE FOOTBAL PLAYERS
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Emory Univ, Atlanta, GA 30322 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1132M-366B
BP A1633
EP A1633
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579102391
ER
PT J
AU Kostis, JB
Liu, J
Cabrera, J
Cheng, JQ
Kostis, WJ
AF Kostis, John B.
Liu, Jie
Cabrera, Javier
Cheng, Jerry Q.
Kostis, William J.
TI FACTORS ASSOCIATED WITH MORE WEIGHT LOSS AFTER INTENSIVE DIETARY
INTERVENTION
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Rutgers Robert Wood Johnson Med Sch, New Brunswick, NJ USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
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 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1144-148
BP A1358
EP A1358
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579102116
ER
PT J
AU Kumar, V
Liao, K
Cheng, C
Yu, S
Kartoun, U
Brettman, A
Gainer, V
Cagan, A
Murphy, S
Savova, G
Chen, P
Szolovits, P
Xia, ZQ
Karlson, E
Plenge, R
Ananthakrishnan, A
Churchill, S
Cai, TX
Kohane, I
Shaw, S
AF Kumar, Vishesh
Liao, Katherine
Cheng, Chun
Yu, Sheng
Kartoun, Uri
Brettman, Ari
Gainer, Vivian
Cagan, Andrew
Murphy, Shawn
Savova, Guergana
Chen, Pei
Szolovits, Peter
Xia, Zongqi
Karlson, Elizabeth
Plenge, Robert
Ananthakrishnan, Ashwin
Churchill, Susanne
Cai, Tianxi
Kohane, Isaac
Shaw, Stanley
TI NATURAL LANGUAGE PROCESSING IMPROVES PHENOTYPIC ACCURACY IN AN
ELECTRONIC MEDICAL RECORD COHORT OF TYPE 2 DIABETES AND CARDIOVASCULAR
DISEASE
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 [Kumar, Vishesh; Liao, Katherine; Cheng, Chun; Yu, Sheng; Kartoun, Uri; Brettman, Ari; Gainer, Vivian; Cagan, Andrew; Murphy, Shawn; Savova, Guergana; Chen, Pei; Szolovits, Peter; Xia, Zongqi; Karlson, Elizabeth; Plenge, Robert; Ananthakrishnan, Ashwin; Churchill, Susanne; Cai, Tianxi; Kohane, Isaac; Shaw, Stanley] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
NR 0
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 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1144-149
BP A1359
EP A1359
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579102117
ER
PT J
AU Le, DTE
Wei, KV
Zhao, Y
Nugent, M
Kaul, S
AF Le, Dai-Trang Elizabeth
Wei, Kevin
Zhao, Yan
Nugent, Matthew
Kaul, Sanjiv
TI RANOLAZINE RELIEVES ISCHEMIA BY DECREASING MYOCARDIAL WORK WITHOUT
ALTERING MYOCARDIAL BLOOD FLOW: INSIGHTS FROM AN EXPERIMENTAL MODEL
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Portland VA Med Ctr, Portland, OR USA.
Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97201 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1279M-365A
BP A1519
EP A1519
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579102277
ER
PT J
AU Lo, JC
Ljubicic, S
Leibiger, B
Chatterjee-Bhowmick, D
Kelly, ME
Cohen, P
Leibiger, I
Banks, A
Flier, J
Bluher, M
Danial, N
Berggren, PO
Spiegelman, BM
AF Lo, James C.
Ljubicic, Sanda
Leibiger, Barbara
Chatterjee-Bhowmick, Diti
Kelly, Molly E.
Cohen, Paul
Leibiger, Ingo
Banks, Alexander
Flier, Jeffrey
Bluher, Matthias
Danial, Nika
Berggren, Per-Olof
Spiegelman, Bruce M.
TI ADIPSIN IS AN ADIPOCYTOKINE DYSREGULATED IN OBESITY/METABOLIC SYNDROME
THAT SUSTAINS CARDIOVASCULAR HEALTH
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Farber Canc Inst, Boston, MA USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 918-03
BP A2144
EP A2144
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579103002
ER
PT J
AU Lu, LY
Jackevicius, C
de Leon, N
Warner, A
Chang, D
Mody, F
AF Lu, Lingyun
Jackevicius, Cynthia
de Leon, Noelle
Warner, Alberta
Chang, Donald
Mody, Freny
TI IMPACT OF A MULTI-DISCIPLINARY HEART FAILURE POST-DISCHARGE MANAGEMENT
CLINIC ON MEDICATION ADHERENCE
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 VA Greater Los Angeles HealthCare Syst, Los Angeles, CA USA.
Western Univ Hlth Sci, Pomona, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1186-180
BP A539
EP A539
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579101197
ER
PT J
AU May, EAB
Bonaca, M
Scirica, B
Kuder, J
Murphy, S
Jarolim, P
Sabatine, M
Morrow, D
AF May, Erin Ann Bohula
Bonaca, Marc
Scirica, Benjamin
Kuder, Julia
Murphy, Sabina
Jarolim, Petr
Sabatine, Marc
Morrow, David
TI GROWTH DIFFERENTIATION FACTOR-15 LEVEL PREDICTS RECURRENT CARDIOVASCULAR
EVENTS IN PATIENTS WITH AN ACUTE CORONARY SYNDROME IN MERLIN-TIMI 36
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
TIMI Study Grp, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 900-08
BP A20
EP A20
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579100021
ER
PT J
AU Mehta, HH
Tan, T
Flynn, A
Jansen, K
Cohen, I
Hung, J
Mehrotra, P
AF Mehta, Hetal H.
Tan, Timothy
Flynn, Aidan
Jansen, Katrijn
Cohen, Ira
Hung, Judy
Mehrotra, Praveen
TI GENDER DIFFERENCES IN PATIENTS WITH PRESERVED EJECTION FRACTION,
LOW-FLOW, LOW-GRADIENT SEVERE AORTIC STENOSIS
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1270-349
BP A2023
EP A2023
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579102781
ER
PT J
AU Natarajan, P
Stitziel, N
Ferencik, M
Hildebrand, L
Gupta, N
Gabriel, S
Hoffmann, U
Kathiresan, S
AF Natarajan, Pradeep
Stitziel, Nathan
Ferencik, Maros
Hildebrand, Lindsey
Gupta, Namrata
Gabriel, Stacey
Hoffmann, Udo
Kathiresan, Sekar
TI CORONARY COMPUTED TOMOGRAPHY ANGIOGRAPHY AND WHOLE GENOME SEQUENCING AS
AN APROACH TO DISCOVER THE GENETIC BASIS OF DISEASE IN A FAMILY PRONE TO
MYOCARDIAL INFARCTION
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Broad Inst, Cambridge, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1156-327
BP A1560
EP A1560
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579102318
ER
PT J
AU Niehaus, E
Tabtabai, S
Sarswat, N
Stone, JR
Gilstrap, L
Maurer, M
Witteles, R
Estep, J
Baran, D
Zucker, M
Feltrin, G
Seldin, D
Semigran, M
AF Niehaus, Emily
Tabtabai, Sara
Sarswat, Nitasha
Stone, James R.
Gilstrap, Lauren
Maurer, Mathew
Witteles, Ronald
Estep, Jerry
Baran, David
Zucker, Mark
Feltrin, Guiseppe
Seldin, David
Semigran, Marc
TI NEED FOR RENAL REPLACEMENT THERAPY AFTER CARDIAC TRANSPLANTATION IN
PATIENTS WITH AL AMYLOIDOSIS IS ASOCIATED WITH POOR SURVIVAL
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 [Niehaus, Emily; Tabtabai, Sara; Sarswat, Nitasha; Stone, James R.; Gilstrap, Lauren; Maurer, Mathew; Witteles, Ronald; Estep, Jerry; Baran, David; Zucker, Mark; Feltrin, Guiseppe; Seldin, David; Semigran, Marc] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1221-182
BP A895
EP A895
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579101553
ER
PT J
AU Perl, L
Zemer-Wassercug, N
Rechavia, E
Vaduganathan, M
Orvin, K
Lerman-Shivek, H
Kornowski, R
Lev, E
AF Perl, Leor
Zemer-Wassercug, Noa
Rechavia, Eldad
Vaduganathan, Muthiah
Orvin, Katia
Lerman-Shivek, Hila
Kornowski, Ran
Lev, Eli
TI VARIABILITY IN RESPONSE TO PRASUGREL AND TICAGRELOR OVER TIME IN
PATIENTS WITH ACUTE CORONARY SYNDROME
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Rabin Med Ctr, Petah Tiqwa, Israel.
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 901-04
BP A23
EP A23
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579100024
ER
PT J
AU Pursnani, A
Lee, A
Mayrhofer, T
Ahmed, W
Uthamalingam, S
Ferencik, M
Bamberg, F
Schlett, C
Udelson, J
Hoffmann, U
Ghoshhajra, B
AF Pursnani, Amit
Lee, Ashley
Mayrhofer, Thomas
Ahmed, Waleed
Uthamalingam, Shanmugam
Ferencik, Maros
Bamberg, Fabian
Schlett, Christopher
Udelson, James
Hoffmann, Udo
Ghoshhajra, Brian
TI INCREMENTAL VALUE OF EARLY RESTING MYOCARDIAL CT PERFUSION ASSESSMENT TO
CARDIAC CT ANGIOGRAPHY FOR PREDICTION OF ACUTE CORONARY SYNDROME IN THE
EMERGENCY DEPARTMENT
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 [Pursnani, Amit; Lee, Ashley; Mayrhofer, Thomas; Ahmed, Waleed; Uthamalingam, Shanmugam; Ferencik, Maros; Bamberg, Fabian; Schlett, Christopher; Udelson, James; Hoffmann, Udo; Ghoshhajra, Brian] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
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 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1250-66
BP A1264
EP A1264
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579102022
ER
PT J
AU Russell, DC
Goodfriend, T
Haworth, R
AF Russell, Douglas C.
Goodfriend, Theodore
Haworth, Robert
TI MECHANISM OF ARRHYTHMOGENESIS INDUCED BY FATTY ACIDS: A ROLE OF
MODIFICATION OF MITOCHONDRIAL CREATINE KINASE AND CITRATE SYNTHASE?
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
Univ Wisconsin, Madison, WI USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1180-91
BP A370
EP A370
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579101028
ER
PT J
AU Sarswat, N
Niehaus, E
Tabtabai, S
Stone, J
Gilstrap, L
Maurer, M
Witteles, R
Estep, J
Baran, D
Zucker, M
Seldin, D
Semigran, M
AF Sarswat, Nitasha
Niehaus, Emily
Tabtabai, Sara
Stone, James
Gilstrap, Lauren
Maurer, Matthew
Witteles, Ronald
Estep, Jerry
Baran, David
Zucker, Mark
Seldin, David
Semigran, Marc
TI PRE-TRANSPLANT CHEMOTHERAPY DOES NOT AFFECT POST TRANSPLANT OUTCOME IN
PATIENTS UNDERGOING OHT FOR AL CARDIOMYOPATHY
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 [Sarswat, Nitasha; Niehaus, Emily; Tabtabai, Sara; Stone, James; Gilstrap, Lauren; Maurer, Matthew; Witteles, Ronald; Estep, Jerry; Baran, David; Zucker, Mark; Seldin, David; Semigran, Marc] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1220-171
BP A884
EP A884
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579101542
ER
PT J
AU Schwartzenberg, S
Goland, S
Sagie, A
AF Schwartzenberg, Shmuel
Goland, Sorel
Sagie, Alik
TI AN UNUSUAL CASE OF CARDIAC AMYLOIDOSIS
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Rabin Med Ctr, Petah Tiqwa, Israel.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1172-04
BP A668
EP A668
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579101326
ER
PT J
AU Singh, P
Tawakol, A
Vucic, E
Emami, H
Fayad, Z
Narula, J
Rudd, J
Morss, A
Swanson, J
Fontanez, S
Traves, P
Tejedor, A
Pimentel-Santillana, M
Mojena, M
Fernaandez-Velasco, M
Bosca, L
AF Singh, Parmanand
Tawakol, Ahmed
Vucic, Esad
Emami, Hamed
Fayad, Zahi
Narula, Jagat
Rudd, James
Morss, Alex
Swanson, Jeffrey
Fontanez, Sara
Traves, Paqui
Tejedor, Alberto
Pimentel-Santillana, Maria
Mojena, Marina
Fernandez-Velasco, Maria
Bosca, Lisardo
TI HYPOXIA-INDUCIBLE FACTOR 1-ALPHA REGULATES ATHEROSCLEROSIS VIA
MACROPHAGE ACTIVATION AND METABOLIC PATHWAYS
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 [Singh, Parmanand; Tawakol, Ahmed; Vucic, Esad; Emami, Hamed; Fayad, Zahi; Narula, Jagat; Rudd, James; Morss, Alex; Swanson, Jeffrey; Fontanez, Sara; Traves, Paqui; Tejedor, Alberto; Pimentel-Santillana, Maria; Mojena, Marina; Fernandez-Velasco, Maria; Bosca, Lisardo] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RI Bosca, Lisardo/A-2059-2008
OI Bosca, Lisardo/0000-0002-0253-5469
NR 0
TC 0
Z9 0
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 918-04
BP A2145
EP A2145
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579103003
ER
PT J
AU Soeda, T
Uemura, S
Dauerman, H
Lee, S
Park, SJ
Jang, YS
Itoh, T
Kuramitsu, S
Domei, T
Barlis, P
Yu, B
Jia, HB
Tian, JW
Vergallo, R
Sining, H
Saito, Y
Jang, IK
AF Soeda, Tsunenari
Uemura, Shiro
Dauerman, Harold
Lee, Stephen
Park, Seung-Jung
Jang, Yang-Soo
Itoh, Tomonori
Kuramitsu, Shoichi
Domei, Takenori
Barlis, Peter
Yu, Bo
Jia, Haibo
Tian, Jinwei
Vergallo, Rocco
Sining, Hu
Saito, Yoshihiko
Jang, Ik-Kyung
TI FREQUENCY, PREDICTORS, AND NATURAL HISTORY OF STENT EDGE DISSECTION: AN
OPTICAL COHERENCE TOMOGRAPHY STUDY
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 2103-309
BP A1793
EP A1793
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579102551
ER
PT J
AU Strom, J
Wimmer, N
Wasfy, J
Yeh, R
AF Strom, Jordan
Wimmer, Neil
Wasfy, Jason
Yeh, Robert
TI RE-EXAMINING THE OPERATOR VOLUME-OUTCOMES RELATIONSHIP IN PERCUTANEOUS
CORONARY INTERVENTION: A SYSTEMATIC REVIEW
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 [Strom, Jordan; Wimmer, Neil; Wasfy, Jason; Yeh, Robert] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 2904-04
BP A1700
EP A1700
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579102458
ER
PT J
AU Tabtabai, S
Niehaus, E
Sarswat, N
Stone, JR
Maurer, M
Witteles, R
Estep, J
Baran, D
Zucker, M
Feltrin, G
Seldin, D
Semigran, M
AF Tabtabai, Sara
Niehaus, Emily
Sarswat, Nitasha
Stone, James R.
Maurer, Mathew
Witteles, Ronald
Estep, Jerry
Baran, David
Zucker, Mark
Feltrin, Guiseppe
Seldin, David
Semigran, Marc
TI REDUCED SURVIVAL IN LAMBDA PREDOMINANT CARDIAC AL AMYLOIDOSIS PATIENTS
AWAITING ORTHOTOPIC HEART TRANSPLANT
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 [Tabtabai, Sara; Niehaus, Emily; Sarswat, Nitasha; Stone, James R.; Maurer, Mathew; Witteles, Ronald; Estep, Jerry; Baran, David; Zucker, Mark; Feltrin, Guiseppe; Seldin, David; Semigran, Marc] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1260-167
BP A930
EP A930
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579101588
ER
PT J
AU Tian, JW
Dauerman, H
Toma, C
Samady, H
Itoh, T
Kuramitsu, S
Domei, T
Jia, HB
Vergallo, R
Soeda, T
Hu, SN
Lee, H
Yu, B
Jang, IK
AF Tian, Jinwei
Dauerman, Harold
Toma, Catalin
Samady, Habib
Itoh, Tomonori
Kuramitsu, Shoichi
Domei, Takenori
Jia, Haibo
Vergallo, Rocco
Soeda, Tsunenari
Hu Sining
Lee, Hang
Yu, Bo
Jang, Ik-Kyung
TI PREVALENCE OF THIN-CAP FIBROATHEROMA AND DEGREE OF STENOSIS: AN OPTICAL
COHERENCE TOMOGRAPHY, INTRAVASCULAR ULTRASOUND, AND ANGIOGRAPHIC STUDY
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Harbin Med Univ, Affiliated Hosp 2, Harbin, Peoples R China.
NR 0
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 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1265-252
BP A258
EP A258
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579100259
ER
PT J
AU Tian, JW
Uemura, S
Park, SJ
Jang, Y
Barlis, P
Lee, S
Jia, HB
Vergallo, R
Soeda, T
Hu, SN
Lee, H
Yu, B
Jang, IK
AF Tian, Jinwei
Uemura, Shiro
Park, Seung-Jung
Jang, Yangsoo
Barlis, Peter
Lee, Stephen
Jia, Haibo
Vergallo, Rocco
Soeda, Tsunenari
Hu, Sining
Lee, Hang
Yu, Bo
Jang, Ik-Kyung
TI DETAILED MORPHOLOGICAL CHARACTERISTICS OF PLAQUES WITH EROSION: A
THREE-VESSEL OCT AND IVUS STUDY
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Harbin Med Univ, Affiliated Hosp 2, Harbin, Peoples R China.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1265-242
BP A248
EP A248
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579100249
ER
PT J
AU Tietjens, J
Whooley, M
Schiller, N
Mishra, R
AF Tietjens, Jeremy
Whooley, Mary
Schiller, Nelson
Mishra, Rakesh
TI THE PROGNOSTIC UTILITY OF AN ECHO-ESTIMATED LEFT VENTRICULAR
END-DIASTOLIC PRESSURE-VOLUME RELATIONSHIP IN PATIENTS WITH STABLE
CORONARY ARTERY DISEASE: THE HEART & SOUL STUDY
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Univ Calif San Francisco, San Francisco, CA 94143 USA.
San Francisco VA Med Ctr, San Francisco, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1129M-363C
BP A975
EP A975
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579101633
ER
PT J
AU Truong, QA
Januzzi, J
Szymonifka, J
Thai, WE
Wai, B
Sharma, U
Sandoval, R
Grunau, Z
Basnet, S
Babatunde, A
Ajijola, O
Singh, J
AF Truong, Quynh A.
Januzzi, James
Szymonifka, Jackie
Thai, Wai-ee
Wai, Bryan
Sharma, Umesh
Sandoval, Ryan
Grunau, Zachary
Basnet, Sandeep
Babatunde, Adefolakemi
Ajijola, Olujimi
Singh, Jagmeet
TI SUPERIORITY OF CORONARY SINUS CARDIAC BIOMARKER SAMPLING OVER PERIPHERAL
VENOUS BLOOD FOR PROGNOSTICATION IN CARDIAC RESYNCHRONIZATION THERAPY:
THE BIOCRT STUDY
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Univ Calif Los Angeles, Los Angeles, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1108-104
BP A314
EP A314
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579100315
ER
PT J
AU Udell, JA
Scirica, B
Cavender, MA
Mosenzon, O
Steg, P
Davidson, J
Hirshberg, B
Im, KK
Raz, I
Bhatt, D
AF Udell, Jacob A.
Scirica, Benjamin
Cavender, Matthew A.
Mosenzon, Ofri
Steg, Philippe
Davidson, Jaime
Hirshberg, Boaz
Im, Kyungah (Kelly)
Raz, Itamar
Bhatt, Deepak
TI BASELINE RENAL FUNCTION AND CARDIOVASCULAR RISK IN PATIENTS TREATED WITH
SAXAGLIPTIN: OBSERVATIONS FROM THE SAVOR-TIMI 53 TRIAL
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div, Boston, MA 02115 USA.
Hadassah Univ Hosp, Dept Internal Med, Diabet Unit, IL-91120 Jerusalem, Israel.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 908-04
BP A1523
EP A1523
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579102281
ER
PT J
AU Wang, Z
Jia, HB
Tian, JW
Vergallo, R
Soeda, T
Aguirre, A
Fujimoto, J
Jang, IK
AF Wang, Zhao
Jia, Haibo
Tian, Jinwei
Vergallo, Rocco
Soeda, Tsunenari
Aguirre, Aaron
Fujimoto, James
Jang, Ik-Kyung
TI COMPUTER AIDED IMAGE ANALYSIS TO ENHANCE IN VIVO DIAGNOSIS OF PLAQUE
EROSION BY INTRAVASCULAR OPTICAL COHERENCE TOMOGRAPHY
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 MIT, Cambridge, MA 02139 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1150-222
BP A91
EP A91
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579100092
ER
PT J
AU Wasfy, MM
Weiner, R
Deluca, J
Wang, F
Berkstresser, B
Hutter, A
Picard, M
Baggish, A
AF Wasfy, Meagan Murphy
Weiner, Rory
Deluca, James
Wang, Francis
Berkstresser, Brant
Hutter, Adolph
Picard, Michael
Baggish, Aaron
TI ENDURANCE EXERCISE-INDUCED CARDIAC REMODELING: NOT ALL SPORTS ARE
CREATED EQUAL
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 [Wasfy, Meagan Murphy; Weiner, Rory; Deluca, James; Wang, Francis; Berkstresser, Brant; Hutter, Adolph; Picard, Michael; Baggish, Aaron] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 927-05
BP A1649
EP A1649
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579102407
ER
PT J
AU Weiner, RB
Wang, F
Hutter, A
Stohr, E
Shave, R
Picard, M
Baggish, A
AF Weiner, Rory B.
Wang, Francis
Hutter, Adolph
Stohr, Eric
Shave, Rob
Picard, Michael
Baggish, Aaron
TI ACUTE VERSUS CHRONIC EXERCISE-INDUCED LEFT VENTRICULAR REMODELING: A
PREVIOUSLY UNRECOGNIZED BIPHASIC PHENOMENON
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 [Weiner, Rory B.; Wang, Francis; Hutter, Adolph; Stohr, Eric; Shave, Rob; Picard, Michael; Baggish, Aaron] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1132M-366A
BP A1632
EP A1632
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579102390
ER
PT J
AU Yeh, RW
Mauri, L
Wolf, R
Lovett, A
Romm, I
Normand, SL
AF Yeh, Robert W.
Mauri, Laura
Wolf, Robert
Lovett, Ann
Romm, Iyah
Normand, Sharon-Lise
TI STEEP DECLINES IN POPULATION RATES OF CORONARY REVASCULARIZATION
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 [Yeh, Robert W.; Mauri, Laura; Wolf, Robert; Lovett, Ann; Romm, Iyah; Normand, Sharon-Lise] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
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 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 915-04
BP A1528
EP A1528
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579102286
ER
PT J
AU Zilinski, JL
Contursi, ME
Isaacs, SK
Lewis, G
Hutter, A
Troyanos, C
D'Hemecourt, PA
Dyer, KS
Baggish, A
AF Zilinski, Jodi L.
Contursi, Miranda E.
Isaacs, Stephanie K.
Lewis, Gregory
Hutter, Adolph
Troyanos, Christopher
D'Hemecourt, Pierre A.
Dyer, K. Sophia
Baggish, Aaron
TI CARDIO-METABOLIC ADAPTATIONS TO MARATHON TRAINING
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 [Zilinski, Jodi L.; Contursi, Miranda E.; Isaacs, Stephanie K.; Lewis, Gregory; Hutter, Adolph; Troyanos, Christopher; D'Hemecourt, Pierre A.; Dyer, K. Sophia; Baggish, Aaron] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
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 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 1
PY 2014
VL 63
IS 12
SU S
MA 1197-356
BP A1659
EP A1659
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CP0QC
UT WOS:000359579102417
ER
PT J
AU Corominas, R
Yang, XP
Lin, GN
Kang, SL
Shen, Y
Ghamsari, L
Broly, M
Rodriguez, M
Tam, S
Trigg, SA
Fan, CY
Yi, S
Tasan, M
Lemmens, I
Kuang, XY
Zhao, N
Malhotra, D
Michaelson, JJ
Vacic, V
Calderwood, MA
Roth, FP
Tavernier, J
Horvath, S
Salehi-Ashtiani, K
Korkin, D
Sebat, J
Hill, DE
Hao, T
Vidal, M
Iakoucheva, LM
AF Corominas, Roser
Yang, Xinping
Lin, Guan Ning
Kang, Shuli
Shen, Yun
Ghamsari, Lila
Broly, Martin
Rodriguez, Maria
Tam, Stanley
Trigg, Shelly A.
Fan, Changyu
Yi, Song
Tasan, Murat
Lemmens, Irma
Kuang, Xingyan
Zhao, Nan
Malhotra, Dheeraj
Michaelson, Jacob J.
Vacic, Vladimir
Calderwood, Michael A.
Roth, Frederick P.
Tavernier, Jan
Horvath, Steve
Salehi-Ashtiani, Kourosh
Korkin, Dmitry
Sebat, Jonathan
Hill, David E.
Hao, Tong
Vidal, Marc
Iakoucheva, Lilia M.
TI Protein interaction network of alternatively spliced isoforms from brain
links genetic risk factors for autism
SO NATURE COMMUNICATIONS
LA English
DT Article
ID DE-NOVO MUTATIONS; COPY-NUMBER VARIATION; GENOME-WIDE ANALYSIS; SPECTRUM
DISORDERS; STRUCTURAL VARIATION; MENTAL-RETARDATION; COMMON VARIANTS;
CONFERRING RISK; SCHIZOPHRENIA; DUPLICATIONS
AB Increased risk for autism spectrum disorders (ASD) is attributed to hundreds of genetic loci. The convergence of ASD variants have been investigated using various approaches, including protein interactions extracted from the published literature. However, these datasets are frequently incomplete, carry biases and are limited to interactions of a single splicing isoform, which may not be expressed in the disease-relevant tissue. Here we introduce a new interactome mapping approach by experimentally identifying interactions between brain-expressed alternatively spliced variants of ASD risk factors. The Autism Spliceform Interaction Network reveals that almost half of the detected interactions and about 30% of the newly identified interacting partners represent contribution from splicing variants, emphasizing the importance of isoform networks. Isoform interactions greatly contribute to establishing direct physical connections between proteins from the de novo autism CNVs. Our findings demonstrate the critical role of spliceform networks for translating genetic knowledge into a better understanding of human diseases.
C1 [Corominas, Roser; Lin, Guan Ning; Kang, Shuli; Iakoucheva, Lilia M.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Yang, Xinping; Shen, Yun; Ghamsari, Lila; Broly, Martin; Rodriguez, Maria; Tam, Stanley; Trigg, Shelly A.; Fan, Changyu; Yi, Song; Calderwood, Michael A.; Roth, Frederick P.; Salehi-Ashtiani, Kourosh; Hill, David E.; Hao, Tong; Vidal, Marc] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA.
[Yang, Xinping; Shen, Yun; Ghamsari, Lila; Broly, Martin; Rodriguez, Maria; Tam, Stanley; Trigg, Shelly A.; Fan, Changyu; Yi, Song; Calderwood, Michael A.; Roth, Frederick P.; Salehi-Ashtiani, Kourosh; Hill, David E.; Hao, Tong; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Yang, Xinping; Shen, Yun; Ghamsari, Lila; Broly, Martin; Rodriguez, Maria; Tam, Stanley; Trigg, Shelly A.; Fan, Changyu; Yi, Song; Calderwood, Michael A.; Roth, Frederick P.; Salehi-Ashtiani, Kourosh; Hill, David E.; Hao, Tong; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Tasan, Murat; Roth, Frederick P.] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada.
[Tasan, Murat; Roth, Frederick P.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 3E1, Canada.
[Tasan, Murat; Roth, Frederick P.] Univ Toronto, Dept Comp Sci, Toronto, ON M5S 3E1, Canada.
[Tasan, Murat; Roth, Frederick P.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5S 3E1, Canada.
[Lemmens, Irma; Tavernier, Jan] Univ Ghent VIB, Dept Med Prot Res, B-9000 Ghent, Belgium.
[Lemmens, Irma; Tavernier, Jan] Univ Ghent, Fac Med & Hlth Sci, Dept Biochem, B-9000 Ghent, Belgium.
[Kuang, Xingyan; Zhao, Nan; Korkin, Dmitry] Univ Missouri, Dept Comp Sci, Columbia, MO 65203 USA.
[Kuang, Xingyan; Zhao, Nan; Korkin, Dmitry] Univ Missouri, Inst Informat, Columbia, MO 65203 USA.
[Malhotra, Dheeraj; Michaelson, Jacob J.; Sebat, Jonathan] Univ Calif San Diego, Beyster Ctr Genom Psychiat Dis, La Jolla, CA 92093 USA.
[Malhotra, Dheeraj; Michaelson, Jacob J.; Sebat, Jonathan] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Vacic, Vladimir] New York Genome Ctr, New York, NY 10013 USA.
[Horvath, Steve] Univ Calif Los Angeles, Dept Human Genet & Biostat, Los Angeles, CA 90095 USA.
RP Hao, T (reprint author), Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA.
EM tong_hao@dfci.harvard.edu; marc_vidal@dfci.harvard.edu; lilyak@ucsd.edu
RI Calderwood, Mike/B-2475-2014; Zhao, Nan/K-4015-2015; Corominas,
Roser/H-4163-2016; Roth, Frederick/H-6308-2011
OI Calderwood, Mike/0000-0001-6475-1418; Zhao, Nan/0000-0002-7897-2374;
Corominas, Roser/0000-0001-8888-5402;
FU NICHD [ARRA R01HD065288]; NIMH [R01MH091350]; NHGRI [R01HG001715];
Ellison Foundation, Boston; Dana-Farber Cancer Institute Strategic
Initiative; NIH [MH076431]; Simons Foundation Autism Research Initiative
[275724]; Canadian Institute for Advanced Research Fellowship; Canada
Excellence Research Chairs Program; National Science Foundation
[DBI-0845196, IOS-1126992]; Fonds voor Wetenschappelijk
Onderzoek-Vlaanderen (FWO); Fonds de la Recherche Scientifique
(FRS-FNRS, Wallonia-Brussels Federation, Belgium)
FX We thank all members of the DFCI Center for Cancer Systems Biology
(CCSB) for helpful discussions throughout the course of this project. We
also thank Dr Joseph Gleeson for valuable comments on the manuscript,
the members of Dr Sebat laboratory for helpful discussions and Abhishek
Bhandari, Ashleigh Schaffer and Naiara Akizu for technical assistance.
This work was supported by NIH grants ARRA R01HD065288 from NICHD to L.
M. I and K. S.-A. and by R01MH091350 from NIMH to L. M. I. and T. H.,
R01HG001715 from NHGRI to M. V., D. E. H., F. P. R. and J.T.; by The
Ellison Foundation, Boston, MA to M. V.; by Institute Sponsored Research
funds from the Dana-Farber Cancer Institute Strategic Initiative to M.
V.; by NIH (MH076431) and the Simons Foundation Autism Research
Initiative (275724) to J.S.; by a Canadian Institute for Advanced
Research Fellowship and the Canada Excellence Research Chairs Program to
F. P. R. and by National Science Foundation grants DBI-0845196 and
IOS-1126992 to D. K. I. L. is a postdoctoral fellow with the Fonds voor
Wetenschappelijk Onderzoek-Vlaanderen (FWO). M. V. is a "Chercheur
Qualifie Honoraire'' from the Fonds de la Recherche Scientifique
(FRS-FNRS, Wallonia-Brussels Federation, Belgium).
NR 69
TC 39
Z9 48
U1 3
U2 31
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD APR
PY 2014
VL 5
AR 3650
DI 10.1038/comms4650
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AG2BZ
UT WOS:000335221700005
ER
PT J
AU Schmitz, S
Ang, KK
Vermorken, J
Haddad, R
Suarez, C
Wolf, GT
Hamoir, M
Machiels, JP
AF Schmitz, Sandra
Ang, Kie Kian
Vermorken, Jan
Haddad, Robert
Suarez, Carlos
Wolf, Gregory T.
Hamoir, Marc
Machiels, Jean-Pascal
TI Targeted therapies for squamous cell carcinoma of the head and neck:
Current knowledge and future directions
SO CANCER TREATMENT REVIEWS
LA English
DT Review
DE Head & neck cancer; Squamous cell carcinoma; Targeted therapies;
Treatment; Molecular biology
ID GROWTH-FACTOR RECEPTOR; PHASE-II TRIAL; PLATINUM-BASED CHEMOTHERAPY;
GENE COPY NUMBER; FACTOR-KAPPA-B; HISTONE DEACETYLASE INHIBITOR;
COOPERATIVE-ONCOLOGY-GROUP; LYMPH-NODE METASTASIS; HUMAN-PAPILLOMAVIRUS;
LUNG-CANCER
AB Despite progress in the therapeutic management of patients with squamous cell carcinoma of the head and neck (SCCHN), the mortality rate of patients presenting with advanced disease remains high. One approach to improve treatment efficacy is to add novel molecular targeted agents to the classical treatment regimens.
Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) have shown clinical benefits in palliative and curative settings. However, only a minority of patients presenting with recurrent or metastatic (RIM) SCCHN have meaningful tumor regression with these agents and virtually all who do develop acquired tumor resistance after a few months of treatment. For these reasons, other inhibitors of EGFR or molecules that interfere with known molecular pathways activated in SCCHN are of considerable interest, either as single agents or in combination with other treatment modalities. In this review, we discuss the different molecular therapeutic approaches explored in SCCHN. We also briefly outline new trial designs that could be used to accelerate the investigation of emerging therapeutic agents in this disease. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Schmitz, Sandra; Hamoir, Marc; Machiels, Jean-Pascal] Catholic Univ Louvain, Dept Med Oncol & Head & Neck Surg, Clin Univ St Luc, Ctr Canc, B-1200 Brussels, Belgium.
[Schmitz, Sandra; Hamoir, Marc; Machiels, Jean-Pascal] Catholic Univ Louvain, Inst Rech Clin & Expt Pole MIRO, B-1200 Brussels, Belgium.
[Ang, Kie Kian] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA.
[Vermorken, Jan] Univ Antwerp Hosp, Dept Med Oncol, B-2650 Edegem, Belgium.
[Haddad, Robert] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Head & Neck Oncol Program, Boston, MA 02215 USA.
[Suarez, Carlos] Hosp Univ Cent Asturias Oviedo, Dept Otolaryngol, Oviedo 33006, Asturias, Spain.
[Wolf, Gregory T.] Univ Michigan Hlth Syst, Dept Otolaryngol Head & Neck Surg, Ann Arbor, MI 48109 USA.
RP Machiels, JP (reprint author), Catholic Univ Louvain, Dept Med Oncol & Head & Neck Surg, Clin Univ St Luc, Ctr Canc, Ave Hippocrate 10, B-1200 Brussels, Belgium.
EM Sandra.schmitz@uclouvain.be; kianang@mdanderson.org;
jan.b.vermorken@uza.be; robert_haddad@dfci.harvard.edu;
csuarezn@hcas.sespa.es; gregwolf@umich.edu; marc.hamoir@uclouvain.be;
jean-pascal.machiels@uclouvain.be
OI Hamoir, Marc/0000-0001-8547-2768
NR 184
TC 28
Z9 28
U1 2
U2 19
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0305-7372
EI 1532-1967
J9 CANCER TREAT REV
JI Cancer Treat. Rev.
PD APR
PY 2014
VL 40
IS 3
BP 390
EP 404
DI 10.1016/j.ctrv.2013.09.007
PG 15
WC Oncology
SC Oncology
GA AB3JT
UT WOS:000331687800006
PM 24176789
ER
PT J
AU Gershman, B
Shui, IM
Stampfer, M
Platz, EA
Gann, PH
Sesso, HL
DuPre, N
Giovannucci, E
Mucci, LA
AF Gershman, Boris
Shui, Irene M.
Stampfer, Meir
Platz, Elizabeth A.
Gann, Peter H.
Sesso, Howard L.
DuPre, Natalie
Giovannucci, Edward
Mucci, Lorelei A.
TI Prediagnostic Circulating Sex Hormones Are Not Associated with Mortality
for Men with Prostate Cancer
SO EUROPEAN UROLOGY
LA English
DT Article
DE Prostate cancer; Testosterone; Androgens; Sex hormones; Mortality
ID SERUM TESTOSTERONE LEVELS; RADICAL PROSTATECTOMY; INDEPENDENT PREDICTOR;
PATHOLOGICAL STAGE; BINDING GLOBULIN; RISK; LEVEL; HYPOGONADISM; MARKER;
INDEX
AB Background: Sex hormones play an important role in the growth and development of the prostate, and low androgen levels have been suggested to carry an adverse prognosis for men with prostate cancer (PCa).
Objective: To examine the association between prediagnostic circulating sex hormones and lethal PCa in two prospective cohort studies, the Physicians' Health Study (PHS) and the Health Professionals Follow-up Study (HPFS).
Design, setting, and participants: We included 963 PCa cases (700 HPFS; 263 PHS) that provided prediagnostic blood samples, in 1982 for PHS and in 1993-1995 for HPFS, in which circulating sex hormone levels were assayed.
Outcome measures and statistical analysis: The primary end point was lethal PCa (defined as cancer-specific mortality or development of metastases), and we also assessed total mortality through March 2011. We used Cox proportional hazards models to evaluate the association of prediagnostic sex hormone levels with time from diagnosis to development of lethal PCa or total mortality.
Results and limitations: PCa cases were followed for a mean of 12.0 +/- 4.9 yr after diagnosis. We confirmed 148 cases of lethal PCa and 421 deaths overall. Using Cox proportional hazard models, we found no significant association between quartile of total testosterone, sex hormone binding globulin (SHBG), SHBG-adjusted testosterone, free testosterone, dihydrotestosterone, androstanediol glucuronide, or estradiol and lethal PCa or total mortality. In subset analyses stratified by Gleason score, TNM stage, age, and interval between blood draw and diagnosis, there was also no consistent association between lethal PCa and sex hormone quartile.
Conclusions: We found no overall association between prediagnostic circulating sex hormones and lethal PCa or total mortality. Our null results suggest that reverse causation may be responsible in prior studies that noted adverse outcomes for men with low circulating androgens. (C) 2013 European Association of Urology. Published by Elsevier B. V. All rights reserved.
C1 [Gershman, Boris] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA.
[Shui, Irene M.; Stampfer, Meir; DuPre, Natalie; Giovannucci, Edward; Mucci, Lorelei A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Stampfer, Meir; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Stampfer, Meir; Giovannucci, Edward; Mucci, Lorelei A.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Stampfer, Meir; Sesso, Howard L.; Giovannucci, Edward; Mucci, Lorelei A.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Gann, Peter H.] Univ Illinois, Dept Pathol, Chicago, IL USA.
[Sesso, Howard L.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA.
RP Mucci, LA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
EM lmucci@hsph.harvard.edu
FU National Institutes of Health/National Cancer Institute [RO1 CA136578,
P01 CA055075, R01 CA133891, R01 CA141298]; DF/HCC SPORE in Prostate
Cancer NIH/NCI [P50 CA90381]; National Cancer Institute NRSA [T32
CA09001]; US Army Prostate Cancer Postdoctoral Fellowship
FX This study was funded in part by grants from the National Institutes of
Health/National Cancer Institute (RO1 CA136578 PI: Mucci; P01 CA055075
PI: Willett; R01 CA133891 PI: Giovannucci; R01 CA141298 PI: Stampfer;
DF/HCC SPORE in Prostate Cancer NIH/NCI P50 CA90381 PI: Kantoff).
Lorelei A. Mucci was a Milken Young Investigator of the Prostate Cancer
Foundation. Irene M. Shui is supported by the National Cancer Institute
NRSA T32 CA09001 (PI: Stampfer) and a US Army Prostate Cancer
Postdoctoral Fellowship.
NR 29
TC 11
Z9 11
U1 2
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
EI 1873-7560
J9 EUR UROL
JI Eur. Urol.
PD APR
PY 2014
VL 65
IS 4
BP 683
EP 689
DI 10.1016/j.eururo.2013.01.003
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA AB3UW
UT WOS:000331716700007
PM 23340241
ER
PT J
AU Gershman, B
Shui, IM
Mucci, LA
AF Gershman, Boris
Shui, Irene M.
Mucci, Lorelei A.
TI Reply from Authors re: Andrea Salonia. Androgens and Prostate Cancer: We
Are Still (Almost) Completely Ignorant. Eur Urol 2014;65:690-1 Androgens
and Prostate Cancer: Clinical Implications and Future Directions
SO EUROPEAN UROLOGY
LA English
DT Editorial Material
ID RADICAL PROSTATECTOMY; TESTOSTERONE
C1 [Gershman, Boris] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA.
[Shui, Irene M.; Mucci, Lorelei A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Mucci, Lorelei A.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Mucci, Lorelei A.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Mucci, LA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
EM lmucci@hsph.harvard.edu
NR 9
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
EI 1873-7560
J9 EUR UROL
JI Eur. Urol.
PD APR
PY 2014
VL 65
IS 4
BP 691
EP 692
DI 10.1016/j.eururo.2013.03.028
PG 3
WC Urology & Nephrology
SC Urology & Nephrology
GA AB3UW
UT WOS:000331716700009
ER
PT J
AU Nguyen, PL
AF Nguyen, Paul L.
TI Androgen-deprivation Therapy and Cardiovascular Harm: Let's Not Throw
Out the Baby with the Bathwater
SO EUROPEAN UROLOGY
LA English
DT Editorial Material
ID PROSTATE-CANCER; ASSOCIATION; SUPPRESSION; RADIATION; DISEASE; MEN
C1 Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA.
RP Nguyen, PL (reprint author), Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA.
EM pnguyen@LROC.harvard.edu
NR 10
TC 4
Z9 4
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
EI 1873-7560
J9 EUR UROL
JI Eur. Urol.
PD APR
PY 2014
VL 65
IS 4
BP 710
EP 712
DI 10.1016/j.eururo.2013.03.002
PG 3
WC Urology & Nephrology
SC Urology & Nephrology
GA AB3UW
UT WOS:000331716700013
PM 23498063
ER
PT J
AU Schutz, FAB
Xie, WL
Donskov, F
Sircar, M
McDermott, DF
Rini, BI
Agarwal, N
Pal, SK
Srinivas, S
Kollmannsberger, C
North, SA
Wood, LA
Vaishampayan, U
Tan, MH
Mackenzie, MJ
Lee, JL
Rha, SY
Yuasa, T
Heng, DYC
Choueiri, TK
AF Schutz, Fabio A. B.
Xie, Wanling
Donskov, Frede
Sircar, Monica
McDermott, David F.
Rini, Brian I.
Agarwal, Neeraj
Pal, Sumanta Kumar
Srinivas, Sandy
Kollmannsberger, Christian
North, Scott A.
Wood, Lori A.
Vaishampayan, Ulka
Tan, Min-Han
Mackenzie, Mary J.
Lee, Jae Lyun
Rha, Sun-Young
Yuasa, Takeshi
Heng, Daniel Y. C.
Choueiri, Toni K.
TI The Impact of Low Serum Sodium on Treatment Outcome of Targeted Therapy
in Metastatic Renal Cell Carcinoma: Results from the International
Metastatic Renal Cell Cancer Database Consortium
SO EUROPEAN UROLOGY
LA English
DT Article
DE Hyponatremia; Renal cell cancer; Anti-VEGF; Prognostic factors
ID INAPPROPRIATE SECRETION; PROGNOSTIC-FACTORS; HYPONATREMIA; CIRRHOSIS;
SURVIVAL; MORTALITY; FAILURE; ASCITES
AB Background: Hyponatremia has been associated with poor survival in many solid tumors and more recently found to be of prognostic and predictive value in metastatic renal cell cancer (mRCC) patients treated with immunotherapy.
Objective: To investigate the influence of baseline hyponatremia in mRCC patients treated with targeted therapy in the International Metastatic Renal Cell Carcinoma Database Consortium.
Design, setting, and participants: Data on 1661 patients treated with first-line vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) targeted therapy for mRCC were available from 18 cancer centers to study the impact of hyponatremia (serum sodium level < 135 mmol/l) on clinical outcomes.
Outcome measurements and statistical analysis: The primary objective was overall survival (OS) and secondary end points included time to treatment failure (TTF) and the disease control rate (DCR). The chi-square test was used to compare the DCR in patients with and without hyponatremia. OS and TTF were estimated with the Kaplan-Meier method and differences between groups were examined by the log-rank test. Multivariable logistic regression (for DCR) and Cox regression (for OS and TTF) were undertaken adjusted for prognostic risk factors.
Results and limitations: Median OS after treatment initiation was 18.5 mo (95% confidence interval [CI], 17.5-19.8 mo), with 552 (33.2%) of patients remaining alive on a median follow-up of 22.1 mo. Median baseline serum sodium was 138 mmol/l (range: 122-159 mmol/l), and hyponatremia was found in 14.6% of patients. On univariate analysis, hyponatremia was associated with shorter OS (7.0 vs 20.9 mo), shorter TTF (2.9 vs 7.4 mo), and lower DCR rate (54.9% vs 78.8%) (p < 0.0001 for all comparisons). In multivariate analysis, these effects remain significant (hazard ratios: 1.51 [95% CI, 1.26-1.80] for OS, and 1.57 [95% CI, 1.34-1.83] for TTF; odds ratio: 0.50 [95% CI, 34-0.72] for DCR; adjusted p < 0.001). Results were similar if sodium was analyzed as a continuous variable (adjusted p < 0.0001 for OS, TTF, and DCR).
Conclusions: This is the largest multi-institutional report to show that hyponatremia is independently associated with a worse outcome in mRCC patients treated with VEGF and mTOR-targeted agents. (C) 2013 Published by Elsevier B.V. on behalf of European Association of Urology.
C1 [Schutz, Fabio A. B.; Xie, Wanling; Choueiri, Toni K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Donskov, Frede] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark.
[Sircar, Monica; Choueiri, Toni K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[McDermott, David F.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Rini, Brian I.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA.
[Agarwal, Neeraj] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
[Pal, Sumanta Kumar] City Hope Comprehens Canc Ctr, Duarte, CA USA.
[Srinivas, Sandy] Stanford Med Ctr, Stanford, CA USA.
[Kollmannsberger, Christian] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
[North, Scott A.] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada.
[Wood, Lori A.] Dalhousie Univ, Halifax, NS, Canada.
[Vaishampayan, Ulka] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
[Tan, Min-Han] Natl Canc Ctr Singapore, Singapore, Singapore.
[Mackenzie, Mary J.] London Reg Canc Program, London, ON, Canada.
[Lee, Jae Lyun] Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea.
[Rha, Sun-Young] Yonsei Univ, Coll Med, Yonsei Canc Ctr, Seoul, South Korea.
[Yuasa, Takeshi] Japanese Fdn Canc Res, Canc Inst Hosp, Tokyo, Japan.
[Heng, Daniel Y. C.] Tom Baker Canc Clin, Calgary, AB, Canada.
RP Choueiri, TK (reprint author), 450 Brookline Ave, Boston, MA 02115 USA.
EM toni_choueiri@dfci.harvard.edu
OI Donskov, Frede/0000-0002-8449-863X
FU Novartis; Pfizer; GlaxoSmithKline; Bayer Korea
FX Toni K. Choueiri certifies that all conflicts of interest, including
specific financial interests and relationships and affiliations relevant
to the subject matter or materials discussed in the manuscript (eg,
employment/affiliation, grants or funding, consultancies, honoraria,
stock ownership or options, expert testimony, royalties, or patents
filed, received, or pending), are the following: Daniel Y.C. Heng has
advisory roles at Aveo, Pfizer, Novartis, and Bayer. Mary J. Mackenzie
has advisory roles at Novartis and Pfizer, and has received research
funding from both. Lori A. Wood has advisory roles at Pfizer and
Novartis, and has received research funding from Pfizer, Novartis, and
GlaxoSmithKline. Ulka Vaishampayan has received honoraria and research
funding from Pfizer, Novartis, and GlaxoSmithKline. Sun-Young Rha has
advisory roles at Novartis, Pfizer, and GlaxoSmithKline, and has
received research funding from Novartis and Bayer Korea. Frede Donskov
has received research funding from Novartis. Christian Kollmannsberger
has advisory roles at Pfizer, Novartis, and GlaxoSmithKline, and has
received honoraria and research funding from Pfizer, Novartis, and
GlaxoSmithKline. Brian I. Rini has advisory role at Pfizer,
GlaxoSmithKline, Aveo, Bayer, Onyx, and has received research funding
from GlaxoSmithKline and Pfizer. Sandy Srinivas has advisory roles at
Pfizer, Novartis, and Genentech. Scott A. North has an advisory role
Pfizer, Novartis, Bayer, and GlaxoSmithKline. Toni K. Choueiri has
received research funding from Pfizer and has advisory roles at Aveo,
Pfizer, Novartis, GlaxoSmithKline, Genentech, Bayer, and Onyx. The other
authors declare that they have no conflicts of interest.
NR 28
TC 14
Z9 14
U1 1
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
EI 1873-7560
J9 EUR UROL
JI Eur. Urol.
PD APR
PY 2014
VL 65
IS 4
BP 723
EP 730
DI 10.1016/j.eururo.2013.10.013
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA AB3UW
UT WOS:000331716700016
PM 24184025
ER
PT J
AU Bellmunt, J
Leow, JJ
AF Bellmunt, Joaquim
Leow, Jeffrey J.
TI Hyponatremia Associated with Worse Outcomes in Metastatic Renal Cell
Cancer: A Potential Target for Intervention?
SO EUROPEAN UROLOGY
LA English
DT Editorial Material
ID CARCINOMA; SURVIVAL; VALIDATION
C1 [Bellmunt, Joaquim; Leow, Jeffrey J.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Bladder Canc Ctr, Boston, MA USA.
RP Bellmunt, J (reprint author), Dana Farber Canc Inst, 450 Brookline Ave DANA 1230, Boston, MA 02215 USA.
EM Joaquim_bellmunt@dfci.harvard.edu
NR 10
TC 1
Z9 1
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
EI 1873-7560
J9 EUR UROL
JI Eur. Urol.
PD APR
PY 2014
VL 65
IS 4
BP 731
EP 732
DI 10.1016/j.eururo.2013.10.057
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA AB3UW
UT WOS:000331716700017
PM 24262101
ER
PT J
AU Keating, NL
Liu, PH
O'Malley, AJ
Freedland, SJ
Smith, MR
AF Keating, Nancy L.
Liu, Pang-Hsiang
O'Malley, A. James
Freedland, Stephen J.
Smith, Matthew R.
TI Androgen-deprivation Therapy and Diabetes Control Among Diabetic Men
with Prostate Cancer
SO EUROPEAN UROLOGY
LA English
DT Article
DE Prostate cancer; Androgen-deprivation therapy; Diabetes
ID CARDIOVASCULAR-DISEASE; ARTERIAL STIFFNESS; BODY-COMPOSITION;
ASSOCIATION; RISK; CARE; MANAGEMENT; VETERANS; MELLITUS; INSULIN
AB Background: Androgen-deprivation therapy (ADT) for prostate cancer (PCa) is associated with decreased insulin sensitivity and increased diabetes risk among nondiabetic men. Few data are available about the effects of ADT on diabetes control among men with diabetes.
Objective: We examined care for men who had diabetes at the time of PCa diagnosis to assess the effect of ADT on diabetes control, as measured by hemoglobin A1c (HbA1c) levels and the intensification of diabetes pharmacotherapy.
Design, setting, and participants: This was an observational cohort study using US Department of Veterans Affairs registry data and administrative data to assess HbA1c levels and intensification of diabetes pharmacotherapy among 2237 pairs of propensitymatched men with PCa and diabetes who were or were not treated with ADT.
Outcome measurements and statistical analysis: We calculated the difference in difference of HbA1c levels at baseline and at 1 and 2 yr in the two groups, compared using a paired Student t test. We used a Cox proportional hazards model to estimate time to intensification of diabetes pharmacotherapy.
Results and limitations: The mean HbA1c at baseline was 7.24 (standard error [SE]: 0.05) for the ADT group and 7.24 (SE: 0.04) for the no-ADT group. HbA1c increased at 1 yr for men treated with ADT to 7.38 (SE: 0.04) and decreased among men not treated with ADT to 7.14 (SE: 0.04), for a difference in differences of +0.24 (p = 0.008). Results were similar at 2 yr (p = 0.03). The worsening HbA1c control occurred despite ADT being associated with an increased hazard of addition of diabetes medication (adjusted hazard ratio: 1.20; 95% confidence interval, 1.09-1.32). The limitation of this study was that it was observational and relied on administrative data.
Conclusions: ADT is associated with worsening of diabetes control and increases in HbA1c levels despite the use of additional diabetes medications. (C) 2013 Published by Elsevier B.V. on behalf of European Association of Urology.
C1 [Keating, Nancy L.] Brigham & Womens Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02115 USA.
[Keating, Nancy L.; Liu, Pang-Hsiang; O'Malley, A. James] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Freedland, Stephen J.] Duke Univ, Sch Med, Div Urol, Dept Surg, Durham, NC USA.
[Freedland, Stephen J.] Durham Vet Affairs Med Ctr, Durham, NC USA.
[Smith, Matthew R.] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA.
RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA.
EM keating@hcp.med.harvard.edu
RI Liu, Michael Pang-Hsiang/B-9903-2015
OI Liu, Michael Pang-Hsiang/0000-0001-8842-2264
FU Prostate Cancer Foundation
FX This study was funded by the Prostate Cancer Foundation. The data were
obtained from the US Department of Veterans Affairs (VA) through the
Office of Policy and Planning as part of a larger evaluation of oncology
care. Neither the sponsor nor the VA had any role in the design and
conduct of the study or the collection, management, analysis,
interpretation of the data, preparation of the manuscript, or decision
to submit the manuscript for publication.
NR 29
TC 14
Z9 14
U1 1
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
EI 1873-7560
J9 EUR UROL
JI Eur. Urol.
PD APR
PY 2014
VL 65
IS 4
BP 816
EP 824
DI 10.1016/j.eururo.2013.02.023
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA AB3UW
UT WOS:000331716700027
PM 23453420
ER
PT J
AU Mosse, YP
Deyell, RJ
Berthold, F
Nagakawara, A
Ambros, PF
Monclair, T
Cohn, SL
Pearson, AD
London, WB
Matthay, KK
AF Mosse, Yael P.
Deyell, Rebecca J.
Berthold, Frank
Nagakawara, Akira
Ambros, Peter F.
Monclair, Tom
Cohn, Susan L.
Pearson, Andrew D.
London, Wendy B.
Matthay, Katherine K.
TI Neuroblastoma in Older Children, Adolescents and Young Adults: A Report
From the International Neuroblastoma Risk Group Project
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE adolescents; autologous hematopoietic cell transplant; neuroblastoma;
young adults
ID INDOLENT COURSE; ONCOLOGY-GROUP; N-MYC; AGE; AMPLIFICATION; EXPERIENCE;
DIAGNOSIS; SURVIVAL; CLASSIFICATION; CHEMOTHERAPY
AB BackgroundNeuroblastoma in older children and adolescents has a distinctive, indolent phenotype, but little is known about the clinical and biological characteristics that distinguish this rare subgroup. Our goal was to determine if an optimal age cut-off exists that defines indolent disease and if accepted prognostic factors and treatment approaches are applicable to older children.
ProcedureUsing data from the International Neuroblastoma Risk Group, among patients 18 months old (n=4,027), monthly age cut-offs were tested to determine the effect of age on survival. The prognostic effect of baseline characteristics and autologous hematopoietic cell transplant (AHCT) for advanced disease was assessed within two age cohorts; 5 to <10 years (n=730) and 10 years (n=200).
ResultsOlder age was prognostic of poor survival, with outcome gradually worsening with increasing age at diagnosis, without statistical evidence for an optimal age cut-off beyond 18 months. Among patients 5 years, factors significantly prognostic of lower event-free survival (EFS) and overall survival (OS) in multivariable analyses were INSS stage 4, MYCN amplification and unfavorable INPC histology classification. Among stage 4 patients, AHCT provided a significant EFS and OS benefit. Following relapse, patients in both older cohorts had prolonged OS compared to those 18 months to <5 years (P<0.0001).
ConclusionsDespite indolent disease and infrequent MYCN amplification, older children with advanced disease have poor survival, without evidence for a specific age cut-off. Our data suggest that AHCT may provide a survival benefit in older children with advanced disease. Novel therapeutic approaches are required to more effectively treat these patients. Pediatr Blood Cancer 2014;61:627-635. (c) 2013 Wiley Periodicals, Inc.
C1 [Mosse, Yael P.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
[Mosse, Yael P.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Deyell, Rebecca J.] Univ British Columbia, British Columbia Childrens Hosp, Div Pediat Hematol & Oncol, Vancouver, BC V5Z 1M9, Canada.
[Berthold, Frank] Univ Cologne, Dept Pediat Hematol & Oncol, D-50931 Cologne, Germany.
[Nagakawara, Akira] Chiba Canc Ctr, Res Inst, Chiba 2608717, Japan.
[Ambros, Peter F.] St Anna Childrens Hosp, Childrens Canc Res Inst, Vienna, Austria.
[Monclair, Tom] Univ Oslo, Rikshosp, Natl Hosp, Dept Surg, N-0027 Oslo, Norway.
[Cohn, Susan L.] Univ Chicago, Sch Med, Chicago, IL 60637 USA.
[Pearson, Andrew D.] Royal Marsden Hosp, Inst Canc Res, Sutton, Surrey, England.
[London, Wendy B.] Boston Childrens Hosp, Boston, MA USA.
[London, Wendy B.] Harvard Univ, Sch Med, Dana Farber Harvard Canc Ctr, Boston, MA USA.
[London, Wendy B.] Childrens Oncol Grp Stat & Data Ctr, Boston, MA USA.
[Matthay, Katherine K.] Univ Calif San Francisco, Sch Med, Dept Pediat, San Francisco, CA 94143 USA.
RP Mosse, YP (reprint author), Childrens Hosp Philadelphia, Colket Translat Res Bldg,3501 Civ Ctr Blvd,Off 30, Philadelphia, PA 19104 USA.
EM mosse@email.chop.edu
OI Cohn, Susan/0000-0001-5749-7650; Ambros, Peter F./0000-0002-5507-7211
FU St. Baldrick's Foundation; Carly Hillman Foundation; Little Heroes
Pediatric Cancer Foundation; Forbeck Foundation; Campini, Conner, and
Dougherty Foundation; UBC Clinician Investigator Program
FX Grant sponsor: St. Baldrick's Foundation; Grant sponsor: Carly Hillman
Foundation; Grant sponsor: Little Heroes Pediatric Cancer Foundation;
Grant sponsor: Forbeck Foundation; Grant sponsor: Campini, Conner, and
Dougherty Foundation; Grant sponsor: UBC Clinician Investigator Program
NR 27
TC 12
Z9 14
U1 0
U2 18
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 APR
PY 2014
VL 61
IS 4
BP 627
EP 635
DI 10.1002/pbc.24777
PG 9
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 303OL
UT WOS:000330683700009
PM 24038992
ER
PT J
AU Robison, NJ
Campigotto, F
Chi, SN
Manley, PE
Turner, CD
Zimmerman, MA
Chordas, CA
Werger, AM
Allen, JC
Goldman, S
Rubin, JB
Isakoff, MS
Pan, WJ
Khatib, ZA
Comito, MA
Bendel, AE
Pietrantonio, JB
Kondrat, L
Hubbs, SM
Neuberg, DS
Kieran, MW
AF Robison, Nathan J.
Campigotto, Federico
Chi, Susan N.
Manley, Peter E.
Turner, Christopher D.
Zimmerman, Mary Ann
Chordas, Christine A.
Werger, Annette M.
Allen, Jeffrey C.
Goldman, Stewart
Rubin, Joshua B.
Isakoff, Michael S.
Pan, Wilbur J.
Khatib, Ziad A.
Comito, Melanie A.
Bendel, Anne E.
Pietrantonio, Jay B.
Kondrat, Laura
Hubbs, Shannon M.
Neuberg, Donna S.
Kieran, Mark W.
TI A Phase II Trial of a Multi-Agent Oral Antiangiogenic (Metronomic)
Regimen in Children With Recurrent or Progressive Cancer
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE angiogenesis; drug resistance; pediatric oncology; phase II clinical
trials
ID LOW-GRADE GLIOMA; TUMOR ANGIOGENESIS; CHEMOTHERAPY; THERAPY;
VINBLASTINE; INHIBITION; GROWTH; THROMBOSPONDIN-1; ETOPOSIDE
AB BackgroundPreclinical models show that an antiangiogenic regimen at low-dose daily (metronomic) dosing may be effective against chemotherapy-resistant tumors. We undertook a prospective, open-label, single-arm, multi-institutional phase II study to evaluate the efficacy of a 5-drug oral regimen in children with recurrent or progressive cancer.
ProcedurePatients 21 years old with recurrent or progressive tumors were eligible. Treatment consisted of continuous oral celecoxib, thalidomide, and fenofibrate, with alternating 21-day cycles of low-dose cyclophosphamide and etoposide. Primary endpoint was to assess, within eight disease strata, activity of the 5-drug regimen over 27 weeks. Blood and urine angiogenesis markers were assessed.
ResultsOne hundred one patients were enrolled; 97 began treatment. Median age was 10 years (range: 191 days-21 years); 47 (49%) were female. Disease strata included high-grade glioma (HGG, 21 patients), ependymoma (19), low-grade glioma (LGG, 12), bone tumors (12), medulloblastoma/primitive neuroectodermal tumor (PNET, 8), leukemia (4), neuroblastoma (3), and miscellaneous tumors (18). Treatment was generally well tolerated; most common toxicities were hematologic. Twenty-four (25%) patients completed 27 weeks therapy without progression, including HGG: 1 (5%), ependymoma: 7 (37%), LGG: 7 (58%), medulloblastoma/PNET: 1, neuroblastoma: 1, and miscellaneous tumors: 7 (39%). Best response was complete response (one patient with medulloblastoma), partial response (12), stable disease (36), progressive disease (47), and inevaluable (1). Baseline serum thrombospondin levels were significantly higher in patients successfully completing therapy than in those who progressed (P=0.009).
ConclusionThe 5-drug regimen was well tolerated. Clinical activity was demonstrated in some but not all tumor strata. Pediatric Blood Cancer 2014;61:636-642. (c) 2013 The Authors Pediatric Blood & Cancer Published by Wiley Periodicals, Inc.
C1 [Robison, Nathan J.; Chi, Susan N.; Manley, Peter E.; Turner, Christopher D.; Zimmerman, Mary Ann; Chordas, Christine A.; Werger, Annette M.; Pietrantonio, Jay B.; Kondrat, Laura; Hubbs, Shannon M.; Kieran, Mark W.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA.
[Robison, Nathan J.; Chi, Susan N.; Manley, Peter E.; Turner, Christopher D.; Zimmerman, Mary Ann; Chordas, Christine A.; Werger, Annette M.; Pietrantonio, Jay B.; Kondrat, Laura; Hubbs, Shannon M.; Kieran, Mark W.] Boston Childrens Hosp, Div Pediat Hematol Oncol, Dept Pediat, Boston, MA USA.
[Campigotto, Federico; Neuberg, Donna S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
[Allen, Jeffrey C.] NYU, Langone Med Ctr, New York, NY USA.
[Goldman, Stewart] Northwestern Univ, Feinberg Sch Med, Lurie Childrens Hosp, Chicago, IL 60611 USA.
[Rubin, Joshua B.] Washington Univ, St Louis Childrens Hosp, Sch Med, Dept Pediat, St Louis, MO 63110 USA.
[Isakoff, Michael S.] Connecticut Childrens Med Ctr, Div Hematol Oncol, Hartford, CT USA.
[Pan, Wilbur J.] UMDNJ Robert Wood Johnson Med Sch, New Brunswick, NJ USA.
[Khatib, Ziad A.] Florida Int Univ, Dept Pediat, Miami Childrens Hosp, Miami, FL 33199 USA.
[Comito, Melanie A.] Penn State Hershey Childrens Hosp, Hershey, PA USA.
[Bendel, Anne E.] Childrens Hosp & Clin Minnesota, Minneapolis, MN USA.
[Bendel, Anne E.] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Los Angeles, CA 90033 USA.
RP Kieran, MW (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Pediat Neurooncol Program, 450 Brookline Ave,SW331, Boston, MA 02215 USA.
EM mark_kieran@dfci.harvard.edu
OI Kieran, Mark/0000-0003-2184-7692
FU Alex's Lemonade Stand Foundation for Childhood Cancer; Stop & Shop
Pediatric Brain Tumor Research Fund; Celgene Pharmaceutical Corporation
FX Grant sponsor: Alex's Lemonade Stand Foundation for Childhood Cancer;
Grant sponsor: Stop & Shop Pediatric Brain Tumor Research Fund; Grant
sponsor: Pediatric Brain Tumor Research and Clinical Fund Support for
data management was provided by Celgene Pharmaceutical Corporation
NR 31
TC 26
Z9 26
U1 0
U2 30
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 APR
PY 2014
VL 61
IS 4
BP 636
EP 642
DI 10.1002/pbc.24794
PG 7
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 303OL
UT WOS:000330683700010
PM 24123865
ER
PT J
AU Borinstein, SC
Barkauskas, DA
Bernstein, M
Goorin, A
Gorlick, R
Krailo, M
Schwartz, CL
Wexler, LH
Toretsky, JA
AF Borinstein, Scott C.
Barkauskas, Donald A.
Bernstein, Mark
Goorin, Allen
Gorlick, Richard
Krailo, Mark
Schwartz, Cindy L.
Wexler, Leonard H.
Toretsky, Jeffrey A.
TI Analysis of Serum Insulin Growth Factor-1 Concentrations in Localized
Osteosarcoma: A Children's Oncology Group Study
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE cancer biology; clinical trials; osteosarcoma
ID METASTATIC OSTEOSARCOMA; EWING SARCOMA; CELL-LINES; IGF-I; RECEPTOR;
EXPRESSION; MALIGNANCIES; PATHWAY; CANCER
AB To investigate the role of insulin-like growth factor-1 (IGF-1), in localized osteosarcoma, serum levels of IGF-1, IGFBP-2, and IGFBP-3 were measured in 224 similarly treated, newly diagnosed patients. We demonstrated that younger patients had lower concentrations of IGF-1 and IGFBP-3 compared to older (P<0.001) along with lower IGFBP-3:IGF-1 and IGFBP-2:IGF-1 ratios (P<0.001). IGFBP-2 did not correlate with age (P=0.16), yet IGFBP-2:IGF-1 ratios were higher in the younger population (P<0.001). These findings show that older patients have higher concentrations of free IGF-1. None of IGF-1, IGFBP-2, nor IGFBP-3 concentrations were associated with event-free nor overall survival. Pediatr Blood Cancer 2014;61:749-752. (c) 2013 Wiley Periodicals, Inc.
C1 [Borinstein, Scott C.] Vanderbilt Univ, Dept Pediat, Div Pediat Hematol Oncol, Nashville, TN 37232 USA.
[Barkauskas, Donald A.; Krailo, Mark] Childrens Oncol Grp, Monrovia, CA USA.
[Barkauskas, Donald A.; Krailo, Mark] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA.
[Bernstein, Mark] Dalhousie Univ, Dept Pediat, Div Hematol Oncol, IWK Hlth Ctr, Halifax, NS, Canada.
[Goorin, Allen] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA.
[Gorlick, Richard] Childrens Hosp Montefiore, Dept Pediat, Div Pediat Hematol Oncol, Bronx, NY USA.
[Schwartz, Cindy L.] Brown Univ, Dept Pediat, Div Pediat Hematol Oncol, Providence, RI 02912 USA.
[Wexler, Leonard H.] Cornell Univ, Dept Pediat, Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Toretsky, Jeffrey A.] Georgetown Univ, Dept Oncol, Washington, DC USA.
[Toretsky, Jeffrey A.] Georgetown Univ, Dept Pediat, Washington, DC 20057 USA.
RP Borinstein, SC (reprint author), Vanderbilt Univ, Dept Pediat, Div Pediat Hematol Oncol, 390 PRB,2200 Pierce Ave, Nashville, TN 37232 USA.
EM scott.c.borinstein@vanderbilt.edu
FU Chair's Grant [U10 CA98543]; NCI, NIH, Bethesda, MD, USA [U24 CA114766];
QuadW Foundaton; AFLAC; Children's Cancer Foundation (Baltimore MD);
Go4theGoal; Dani's Foundation; Alex's Lemonade Stand Foundation; Liddy
Shriver Sarcoma Initiative, Burroughs Wellcome Clinical Scientist Award
in Translational Research; NIH [R01CA88004, R01CA133662, R01CA138212,
RC4CA156509]
FX Grant sponsor: Chair's Grant; Grant number: U10 CA98543; Grant sponsor:
NCI, NIH, Bethesda, MD, USA; Grant number: U24 CA114766; Grant sponsor:
QuadW Foundaton; Grant sponsor: AFLAC; Grant sponsor: Children's Cancer
Foundation (Baltimore MD); Grant sponsor: Go4theGoal; Grant sponsor:
Dani's Foundation; Grant sponsor: Alex's Lemonade Stand Foundation;
Grant sponsor: Liddy Shriver Sarcoma Initiative, Burroughs Wellcome
Clinical Scientist Award in Translational Research; Grant sponsor: NIH;
Grant numbers: R01CA88004; R01CA133662; R01CA138212; RC4CA156509
NR 20
TC 3
Z9 5
U1 0
U2 9
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 APR
PY 2014
VL 61
IS 4
BP 749
EP 752
DI 10.1002/pbc.24778
PG 4
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 303OL
UT WOS:000330683700031
PM 24178953
ER
PT J
AU Birdsill, AC
Koscik, RL
Jonaitis, EM
Johnson, SC
Okonkwo, OC
Hermann, BP
Larue, A
Sager, MA
Bendlin, BB
AF Birdsill, Alex C.
Koscik, Rebecca L.
Jonaitis, Erin M.
Johnson, Sterling C.
Okonkwo, Ozioma C.
Hermann, Bruce P.
Larue, Asenath
Sager, Mark A.
Bendlin, Barbara B.
TI Regional white matter hyperintensities: aging, Alzheimer's disease risk,
and cognitive function
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE White matter hyperintensities; Aging; Processing speed; Cognition; MRI
ID EXECUTIVE FUNCTION; EPISODIC MEMORY; OLDER-ADULTS; ROTTERDAM SCAN;
LESIONS; MRI; AGE; BRAIN; APOE; HYPERTENSION
AB White matter hyperintensities (WMH) of presumed vascular origin, as seen on T2-weighted fluid attenuated inversion recovery magnetic resonance imaging, are known to increase with age and are elevated in Alzheimer's disease (AD). The cognitive implications of these common markers are not well understood. Previous research has primarily focused on global measures of WMH burden and broad localizations that contain multiple white matter tracts. The aims of this study were to determine the pattern of WMH accumulation with age, risk for AD, and the relationship with cognitive function utilizing a voxel-wise analysis capable of identifying specific white matter regions. A total of 349 participants underwent T1-weighted and high-resolution T2-weighted fluid attenuated inversion recovery magnetic resonance imaging and neuropsychological testing. Increasing age and lower cognitive speed and flexibility (a component of executive function), were both significantly associated with regional WMH throughout the brain. When age was controlled, lower cognitive speed and flexibility was independently associated with WMH in the superior corona radiata. Apolipoprotein E epsilon 4 and parental family history of AD were not associated with higher burden of WMH. The results contribute to a larger body of literature suggesting that white matter measures are linked with processing speed, and illustrate the utility of voxel-wise analysis in understanding the effect of lesion location on cognitive function. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Birdsill, Alex C.; Johnson, Sterling C.; Okonkwo, Ozioma C.; Bendlin, Barbara B.] William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI USA.
[Birdsill, Alex C.; Johnson, Sterling C.; Okonkwo, Ozioma C.; Sager, Mark A.; Bendlin, Barbara B.] Univ Wisconsin, Wisconsin Alzheimers Dis Res Ctr, Dept Med, Madison, WI 53792 USA.
[Koscik, Rebecca L.; Jonaitis, Erin M.; Hermann, Bruce P.; Larue, Asenath; Sager, Mark A.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Inst, Madison, WI 53792 USA.
RP Bendlin, BB (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Ctr Clin Sci J5 1M, 600 Highland Ave, Madison, WI 53792 USA.
EM bbb@medicine.wisc.edu
OI Bendlin, Barbara/0000-0002-0580-9875
FU Alzheimer's Association [NIRG-09-132626]; National Institute on Aging
[R01 AG027161, ADRC P50 AG033514, R01 AG021155, R01 AG037639]; Veteran's
Administration Merit Review award [I01CX000165]
FX This project was supported by the Alzheimer's Association,
NIRG-09-132626, the National Institute on Aging (R01 AG027161 [MAS],
ADRC P50 AG033514 [SA], R01 AG021155 [SCJ], R01 AG037639 [BBB]), and by
the Veteran's Administration Merit Review award I01CX000165. The project
was also facilitated by the facilities and resources at the Geriatric
Research, Education, and Clinical Center (GRECC) of the William S.
Middleton Memorial Veterans Hospital, Madison, WI, USA. GRECC MS #
2013-03. The authors gratefully acknowledge Nancy Davenport-Sis, Amy
Hawley, Jennifer Bond, Caitlin Cleary, Jennifer Oh, Chuck Illingworth,
and the support of researchers and staff at the Waisman Center,
University of Wisconsin-Madison, for their assistance in recruitment,
data collection, and data analysis. Above all, the authors wish to thank
our dedicated volunteers for their participation in this research.
NR 61
TC 17
Z9 17
U1 1
U2 39
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 APR
PY 2014
VL 35
IS 4
BP 769
EP 776
DI 10.1016/j.neurobiolaging.2013.10.072
PG 8
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 297VN
UT WOS:000330283300007
PM 24199958
ER
PT J
AU Ghosh, SK
Yigit, MV
Uchida, M
Ross, AW
Barteneva, N
Moore, A
Medarova, Z
AF Ghosh, Subrata K.
Yigit, Mehmet V.
Uchida, Masashi
Ross, Alana W.
Barteneva, Natalie
Moore, Anna
Medarova, Zdravka
TI Sequence-dependent combination therapy with doxorubicin and a
survivin-specific small interfering RNA nanodrug demonstrates efficacy
in models of adenocarcinoma
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE small interfering RNA; nanodrug; breast cancer; pancreatic cancer;
doxorubicin
ID BREAST-CANCER CELLS; IN-VIVO; TUMOR RESPONSE; APOPTOSIS; EXPRESSION;
DELIVERY; SIRNA; RESISTANCE; STRATEGY; AGENTS
AB The clinical management of cancer reflects a balance between treatment efficacy and toxicity. While typically, combination therapy improves response rate and time to progression compared with sequential monotherapy, it causes increased toxicity. Consequently, in cases of advanced cancer, emerging guidelines recommend sequential monotherapy, as a means to enhance quality of life. An alternative approach that could overcome nonspecific toxicity while retaining therapeutic efficacy, involves the combination of chemotherapy with targeted therapy. In the current study, we tested the hypothesis that combination therapy targeting survivin (BIRC5) and low-dose doxorubicin (Dox) will show enhanced therapeutic potential in the treatment of cancer, as compared to monotherapy with Dox. We demonstrate in both in vitro and in vivo models of breast cancer that combination therapy with a low dose of Dox and an anti-survivin siRNA nanodrug (MN-siBIRC5) is superior to mono-therapy with either low- or high-dose Dox alone. Importantly, therapeutic efficacy showed prominent sequence dependence. Induction of apoptosis was observed only when the cells were treated with Dox followed by MN-siBIRC5, whereas the reverse sequence abrogated the benefit of the drug combination. In vivo, confirmation of successful sequence dependent combination therapy was demonstrated in a murine xenograft model of breast cancer. Finally, to determine if the observed effect is not limited to breast cancer, we extended our studies to a murine xenograft model of pancreatic adenocarcinoma and found similar outcomes as shown for breast cancer.
What's new? Standard combination chemotherapy can overcome drug resistance and delay cancer progression, but it is also more toxic than the use of single drugs alone. This study suggests, however, that combination therapy involving a chemotherapeutic agent and molecularly targeted therapy may have the ability to both retain therapeutic efficacy and preserve quality of life. In vitro and in vivo experiments reveal that sequence-dependent therapy with low-dose doxorubicin and an anti-survivin siRNA nanodrug can have profound effects on primary tumor growth and circumvent the issues of toxicity and morbidity associated with standard chemotherapy.
C1 [Ghosh, Subrata K.; Yigit, Mehmet V.; Uchida, Masashi; Ross, Alana W.; Moore, Anna; Medarova, Zdravka] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Mol Imaging Lab, MGH HST Athinoula A Martinos Ctr Biomed Imaging,D, Boston, MA USA.
RP Medarova, Z (reprint author), Massachusetts Gen Hosp, Dept Radiol, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Rm 1-424,Bldg 75,13th St, Charlestown, MA 02129 USA.
EM zmedarova@partners.org
FU National Cancer Institute [R00CA129070, R01CA16346101A1]; Breast Cancer
Alliance
FX Grant sponsor: National Cancer Institute; Grant numbers: R00CA129070,
R01CA16346101A1; Grant sponsor: Breast Cancer Alliance
NR 28
TC 10
Z9 11
U1 1
U2 54
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD APR 1
PY 2014
VL 134
IS 7
BP 1758
EP 1766
DI 10.1002/ijc.28499
PG 9
WC Oncology
SC Oncology
GA 287YW
UT WOS:000329579500024
PM 24114765
ER
PT J
AU Shenoy, ES
Paras, ML
Noubary, F
Walensky, RP
Hooper, DC
AF Shenoy, Erica S.
Paras, Molly L.
Noubary, Farzad
Walensky, Rochelle P.
Hooper, David C.
TI Natural history of colonization with methicillin-resistant
Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus
(VRE): a systematic review
SO BMC INFECTIOUS DISEASES
LA English
DT Review
DE MRSA; VRE; Colonization; Carrier; Contact precautions
ID RANDOMIZED CONTROLLED-TRIAL; CHRONIC-HEMODIALYSIS PATIENTS;
POLYMERASE-CHAIN-REACTION; HEALTH-CARE SETTINGS; CONTACT PRECAUTIONS;
RISK-FACTORS; ANTIBIOTIC-THERAPY; UNITED-STATES; NOSOCOMIAL
TRANSMISSION; INTRANASAL MUPIROCIN
AB Background: No published systematic reviews have assessed the natural history of colonization with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE). Time to clearance of colonization has important implications for patient care and infection control policy.
Methods: We performed parallel searches in OVID Medline for studies that reported the time to documented clearance of MRSA and VRE colonization in the absence of treatment, published between January 1990 and July 2012.
Results: For MRSA, we screened 982 articles, identified 16 eligible studies (13 observational studies and 3 randomized controlled trials), for a total of 1,804 non-duplicated subjects. For VRE, we screened 284 articles, identified 13 eligible studies (12 observational studies and 1 randomized controlled trial), for a total of 1,936 non-duplicated subjects. Studies reported varying definitions of clearance of colonization; no study reported time of initial colonization. Studies varied in the frequency of sampling, assays used for sampling, and follow-up period. The median duration of total follow-up was 38 weeks for MRSA and 25 weeks for VRE. Based on pooled analyses, the model-estimated median time to clearance was 88 weeks after documented colonization for MRSA-colonized patients and 26 weeks for VRE-colonized patients. In a secondary analysis, clearance rates for MRSA and VRE were compared by restricting the duration of follow-up for the MRSA studies to the maximum observed time point for VRE studies (43 weeks). With this restriction, the model-fitted median time to documented clearance for MRSA would occur at 41 weeks after documented colonization, demonstrating the sensitivity of the pooled estimate to length of study follow-up.
Conclusions: Few available studies report the natural history of MRSA and VRE colonization. Lack of a consistent definition of clearance, uncertainty regarding the time of initial colonization, variation in frequency of sampling for persistent colonization, assays employed and variation in duration of follow-up are limitations of the existing published literature. The heterogeneity of study characteristics limits interpretation of pooled estimates of time to clearance, however, studies included in this review suggest an increase in documented clearance over time, a result which is sensitive to duration of follow-up.
C1 [Shenoy, Erica S.] Massachusetts Gen Hosp, Div Infect Dis, Infect Control Unit, Boston, MA 02114 USA.
[Shenoy, Erica S.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA.
[Shenoy, Erica S.; Paras, Molly L.; Walensky, Rochelle P.; Hooper, David C.] Harvard Univ, Sch Med, Boston, MA USA.
[Paras, Molly L.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Noubary, Farzad] Tufts Clin & Translat Sci Inst, Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA.
[Noubary, Farzad] Tufts Univ, Boston, MA 02111 USA.
[Walensky, Rochelle P.] Massachusetts Gen & Brigham & Womens Hosp, Div Infect Dis, Boston, MA USA.
[Walensky, Rochelle P.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA.
[Hooper, David C.] Massachusetts Gen Hosp, Infect Control Unit, Div Infect Dis, Boston, MA 02114 USA.
RP Shenoy, ES (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Infect Control Unit, Boston, MA 02114 USA.
EM eshenoy@partners.org
OI Walensky, Rochelle P./0000-0002-8795-379X
FU The Institute for Health Technology Studies; NIH [T32 A107061]; MGH
Clinical Innovation Award; CFAR [NIH P30 AI060354]; Harvard Catalyst \
The Harvard Clinical and Translational Science Center (National Center
for Research Resources, National Institutes of Health) [8UL1TR000170-05,
1 UL1 RR02578]; Harvard Catalyst \ The Harvard Clinical and
Translational Science Center (National Center for Advancing
Translational Sciences, National Institutes of Health) [8UL1TR000170-05,
1 UL1 RR02578]
FX Support for this work provided by: The Institute for Health Technology
Studies; NIH T32 A107061; 2010 MGH Clinical Innovation Award;
Departmental Funds; CFAR (NIH P30 AI060354) and the Harvard Catalyst
vertical bar The Harvard Clinical and Translational Science Center
(National Center for Research Resources and the National Center for
Advancing Translational Sciences, National Institutes of Health Awards
8UL1TR000170-05 and 1 UL1 RR02578). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 56
TC 15
Z9 17
U1 4
U2 24
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2334
J9 BMC INFECT DIS
JI BMC Infect. Dis.
PD MAR 31
PY 2014
VL 14
AR 177
DI 10.1186/1471-2334-14-177
PG 13
WC Infectious Diseases
SC Infectious Diseases
GA AG5PD
UT WOS:000335470000003
PM 24678646
ER
PT J
AU Tache, Y
AF Tache, Yvette
TI HANS SELYE AND THE STRESS RESPONSE: FROM "THE FIRST MEDIATOR" TO THE
IDENTIFICATION OF THE HYPOTHALAMIC CORTICOTROPIN-RELEASING FACTOR
SO IDEGGYOGYASZATI SZEMLE-CLINICAL NEUROSCIENCE
LA English
DT Article
DE corticotropin releasing factor; hypothalamus; Selye; stress
ID RECEPTORS; CRF
AB Selye pioneered the stress concept that is ingrained in the vocabulary of daily life. This was originally build on experimental observations that divers noxious agents can trigger a similar triad of endocrine (adrenal enlargement), immune (involution of thymus) and gut (gastric erosion formation) responses as reported in a letter to Nature in 1936. Subsequently, he articulated the underlying mechanisms and hypothesized the existence of a "first mediator" in the hypothalamus able to orchestrate this bodily changes. However he took two generations to identify this mediator. The Nobel Laureate, Roger Guillemin, alpha former Selye's PhD student, demonstrated in 1955 the existence of a hypothalamic factor that elicited adrenocorticotropic hormone release from the rat pituitary and named it corticotropin releasing factor (CRF). In 1981, Wylie Vale, a former Guillemin's Ph Student, characterized CRF as 41 amino acid and cloned the CRF1 and CRF2 receptors. This paves the way to experimental studies establishing that the activation of the CRF signaling pathways in the brain plays a key role in mediating the stress-related endocrine, behavioral, autonomic and visceral responses. The unraveling of the biochemical coding of stress is rooted in Selye legacy continues to have increasing impact on the scientific community.
C1 [Tache, Yvette] Univ Calif Los Angeles, Dept Med, CURE Digest Dis Res Ctr, Ctr Neurobiol Stress,Digest Dis Div, Los Angeles, CA 90024 USA.
[Tache, Yvette] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA.
RP Tache, Y (reprint author), Univ Calif Los Angeles, Dept Med, CURE Digest Dis Res Ctr, Ctr Neurobiol Stress,Digest Dis Div, Los Angeles, CA 90024 USA.
EM yvette.tache@va.gov
NR 13
TC 0
Z9 0
U1 4
U2 8
PU LITERATURA MEDICA
PI BUDAPEST
PA MARGIT KRT 31-33, BUDAPEST, 1024, HUNGARY
SN 0019-1442
J9 IDEGGYOGY SZEMLE
JI Ideggyogy. Szle.
PD MAR 30
PY 2014
VL 67
IS 3-4
BP 95
EP 98
PG 4
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AX1BU
UT WOS:000346684200007
PM 26118248
ER
PT J
AU Black, AC
McMahon, TJ
Rosenheck, RA
Ball, SA
Ries, RK
Ames, D
Rosen, MI
AF Black, Anne C.
McMahon, Thomas J.
Rosenheck, Robert A.
Ball, Samuel A.
Ries, Richard K.
Ames, Donna
Rosen, Marc I.
TI Development of the Clinician Assessment of Financial Incapability (CAFI)
SO PSYCHIATRY RESEARCH
LA English
DT Article
DE Assessment; Financial capability; Representative payee; Social Security;
Psychiatric; Income
ID REPRESENTATIVE PAYEE PROGRAM; SEVERE MENTAL-ILLNESS; SUBSTANCE USE
DISORDERS; MONEY MANAGEMENT; BENEFICIARIES; ADDICTION; LEVERAGE;
THERAPY; CLIENTS; ADULTS
AB The Social Security Administration (SSA) provides financial support to adults disabled by psychiatric conditions to provide for their basic needs. For beneficiaries identified as incapable of managing their funds, representative payee assignment is mandated: However, studies indicate that the current SSA method of determining capability leads to idiosyncratic payee assignment, with a tendency to under-identify beneficiaries needing payees. Over two phases with data from 78 mental health clinicians treating 134 patient-beneficiaries, we describe the development of a new assessment, the Clinician Assessment of Financial Incapability (CAFI). Item generation, subscale construction, and preliminary assessments of validity are described. We also describe the simultaneous development of a criterion measure of capability, a comprehensive review of all data. Experts identified four subscales mapping to four criteria of incapability; factor analysis provided support for this item structure. Close to one-half of patients were determined to be incapable by review of all data. CAFI and SSA methods correctly classified 73% of cases, but errors with CAFI were more evenly distributed between false negatives and false positives. The implications of classification error are considered, and advantages of CAFI over the SSA method are enumerated. Plans for future instrument revision are briefly described. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
C1 [Black, Anne C.; McMahon, Thomas J.; Rosenheck, Robert A.; Ball, Samuel A.; Rosen, Marc I.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
[Black, Anne C.; Rosen, Marc I.] VA Connecticut Healthcare Syst, West Haven, CT 06516 USA.
[Ries, Richard K.] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA.
[Ames, Donna] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA.
[Ames, Donna] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA.
RP Black, AC (reprint author), VA Connecticut Healthcare Syst, 950 Campbell Ave 116A-4, West Haven, CT 06516 USA.
EM anne.black@yale.edu
FU National Institute on Drug Abuse [R01 DA025613]
FX This study was funded by the National Institute on Drug Abuse R01
DA025613 (MIR).
NR 30
TC 4
Z9 4
U1 3
U2 12
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0165-1781
J9 PSYCHIAT RES
JI Psychiatry Res.
PD MAR 30
PY 2014
VL 215
IS 3
BP 784
EP 789
DI 10.1016/j.psychres.2014.01.021
PG 6
WC Psychiatry
SC Psychiatry
GA AE2AU
UT WOS:000333776500045
PM 24495575
ER
PT J
AU Noel, PH
Parchman, ML
Palmer, RF
Romero, RL
Leykum, LK
Lanham, HJ
Zeber, JE
Bowers, KW
AF Noel, Polly H.
Parchman, Michael L.
Palmer, Ray F.
Romero, Raquel L.
Leykum, Luci K.
Lanham, Holly J.
Zeber, John E.
Bowers, Krista W.
TI Alignment of patient and primary care practice member perspectives of
chronic illness care: a cross-sectional analysis
SO BMC FAMILY PRACTICE
LA English
DT Article
DE Chronic care; Primary care; Patient surveys
ID PREVENTIVE SERVICE DELIVERY; SELF-MANAGEMENT; UNDERSTANDING PRACTICE;
RANDOMIZED-TRIAL; CLINICAL-TRIAL; QUALITY; MODEL; OUTCOMES;
SATISFACTION; BEHAVIORS
AB Background: Little is known as to whether primary care teams' perceptions of how well they have implemented the Chronic Care Model (CCM) corresponds with their patients' own experience of chronic illness care. We examined the extent to which practice members' perceptions of how well they organized to deliver care consistent with the CCM were associated with their patients' perceptions of the chronic illness care they have received.
Methods: Analysis of baseline measures from a cluster randomized controlled trial testing a practice facilitation intervention to implement the CCM in small, community-based primary care practices. All practice "members" (i.e., physician providers, non-physician providers, and staff) completed the Assessment of Chronic Illness Care(ACIC) survey and adult patients with 1 or more chronic illnesses completed the Patient Assessment of Chronic Illness Care (PACIC) questionnaire.
Results: Two sets of hierarchical linear regression models accounting for nesting of practice members (N = 283) and patients (N = 1,769) within 39 practices assessed the association between practice member perspectives of CCM implementation (ACIC scores) and patients' perspectives of CCM (PACIC). ACIC summary score was not significantly associated with PACIC summary score or most of PACIC subscale scores, but four of the ACIC subscales [Self- management Support (p < 0.05); Community Linkages (p < 0.02), Delivery System Design (p < 0.02), and Organizational Support (p < 0.02)] were consistently associated with PACIC summary score and the majority of PACIC subscale scores after controlling for patient characteristics. The magnitude of the coefficients, however, indicates that the level of association is weak.
Conclusions: The ACIC and PACIC scales appear to provide complementary and relatively unique assessments of how well clinical services are aligned with the CCM. Our findings underscore the importance of assessing both patient and practice member perspectives when evaluating quality of chronic illness care.
Trial registration: NCT00482768
C1 [Noel, Polly H.; Leykum, Luci K.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
[Noel, Polly H.; Palmer, Ray F.; Romero, Raquel L.; Leykum, Luci K.; Lanham, Holly J.; Bowers, Krista W.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
[Parchman, Michael L.] MacColl Ctr Healthcare Innovat, Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA 98101 USA.
[Lanham, Holly J.] Univ Texas Austin, McCombs Sch Business, Austin, TX 78712 USA.
[Zeber, John E.] Cent Texas Vet Hlth Care Syst, Temple, TX 76504 USA.
[Zeber, John E.] Scott & White Healthcare Ctr Appl Hlth Res, Temple, TX 76508 USA.
RP Noel, PH (reprint author), South Texas Vet Hlth Care Syst, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA.
EM noelp@uthscsa.edu
OI Parchman, Michael/0000-0001-7129-2889
FU National Institute of Health (NIDDK) [R18DK075692]; Department of
Veterans Affairs, Veterans Health Administration, Health Services
Research and Development Service; South Texas Veterans Health Care
System
FX The research reported here was supported by the National Institute of
Health (NIDDK Grant R18DK075692) and the Department of Veterans Affairs,
Veterans Health Administration, Health Services Research and Development
Service. Investigator salary support was also provided through the South
Texas Veterans Health Care System. The views expressed in this article
are those of the authors and do not necessarily reflect the position or
policy of the Department of Veterans Affairs. The study team would like
to acknowledge technical assistance from Poomachand Veerapaneni, Janet
Hendricks, and Paul Hartman, and the assistance of Amr Mazen Arar,
Brendan Nadeau, and Alan B. Romero in collecting patient surveys, as
well as the primary care practices and their anonymous patients who
participated in the project. We would also like to posthumously
acknowledge the overall contributions of Dr. Nedal H. Arar, who was an
integral member of the study team.
NR 39
TC 5
Z9 5
U1 1
U2 11
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2296
J9 BMC FAM PRACT
JI BMC Fam. Pract.
PD MAR 29
PY 2014
VL 15
AR 57
DI 10.1186/1471-2296-15-57
PG 8
WC Primary Health Care; Medicine, General & Internal
SC General & Internal Medicine
GA AF4TJ
UT WOS:000334706700001
PM 24678983
ER
PT J
AU Jehle, K
Cato, L
Neeb, A
Muhle-Goll, C
Jung, N
Smith, EW
Buzon, V
Carbo, LR
Estebanez-Perpina, E
Schmitz, K
Fruk, L
Luy, B
Chen, Y
Cox, MB
Brase, S
Brown, M
Cato, ACB
AF Jehle, Katja
Cato, Laura
Neeb, Antje
Muhle-Goll, Claudia
Jung, Nicole
Smith, Emmanuel W.
Buzon, Victor
Carbo, Laia R.
Estebanez-Perpina, Eva
Schmitz, Katja
Fruk, Ljiljana
Luy, Burkhard
Chen, Yu
Cox, Marc B.
Braese, Stefan
Brown, Myles
Cato, Andrew C. B.
TI Coregulator Control of Androgen Receptor Action by a Novel Nuclear
Receptor-binding Motif
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Androgen Receptor; Chromatin Immunoprecipitation (ChiP); Gene
Expression; Ligand-binding Protein; Prostate Cancer; Activation
Function-2 (AF-2); Androgen Receptor Ligand-binding Domain (AR-LBD);
Bag-1L; Binding Function-3 (BF-3); Nuclear Receptors
ID RESISTANT PROSTATE-CANCER; HEAT-SHOCK-PROTEIN; VITAMIN-D-RECEPTOR;
LIGAND-BINDING; TRANSACTIVATION FUNCTION; COACTIVATOR INTERACTIONS;
GLUCOCORTICOID-RECEPTOR; NUCLEOTIDE EXCHANGE; GENE-EXPRESSION; IN-VIVO
AB Background: The interaction surface of coactivators and the androgen receptor (AR) is an important target for prostate cancer therapeutics. Results: A new interface formed by binding of the sequence (GARRPR) and the allosteric pocket (BF-3) of the AR has been identified. Conclusion: GARRPR binding modulates AR activity. Significance: The GARRPR/BF-3 interaction is a novel regulatory hub for AR activity.
The androgen receptor (AR) is a ligand-activated transcription factor that is essential for prostate cancer development. It is activated by androgens through its ligand-binding domain (LBD), which consists predominantly of 11 -helices. Upon ligand binding, the last helix is reorganized to an agonist conformation termed activator function-2 (AF-2) for coactivator binding. Several coactivators bind to the AF-2 pocket through conserved LXXLL or FXXLF sequences to enhance the activity of the receptor. Recently, a small compound-binding surface adjacent to AF-2 has been identified as an allosteric modulator of the AF-2 activity and is termed binding function-3 (BF-3). However, the role of BF-3 in vivo is currently unknown, and little is understood about what proteins can bind to it. Here we demonstrate that a duplicated GARRPR motif at the N terminus of the cochaperone Bag-1L functions through the BF-3 pocket. These findings are supported by the fact that a selective BF-3 inhibitor or mutations within the BF-3 pocket abolish the interaction between the GARRPR motif(s) and the BF-3. Conversely, amino acid exchanges in the two GARRPR motifs of Bag-1L can impair the interaction between Bag-1L and AR without altering the ability of Bag-1L to bind to chromatin. Furthermore, the mutant Bag-1L increases androgen-dependent activation of a subset of AR targets in a genome-wide transcriptome analysis, demonstrating a repressive function of the GARRPR/BF-3 interaction. We have therefore identified GARRPR as a novel BF-3 regulatory sequence important for fine-tuning the activity of the AR.
C1 [Jehle, Katja; Neeb, Antje; Braese, Stefan; Cato, Andrew C. B.] Karlsruhe Inst Technol, Inst Toxicol & Genet, D-76344 Eggenstein Leopoldshafen, Germany.
[Cato, Laura; Brown, Myles] Harvard Univ, Sch Med, Div Mol & Cellular Oncol, Dept Med Oncol, Boston, MA 02215 USA.
[Cato, Laura; Brown, Myles] Harvard Univ, Sch Med, Ctr Funct Canc Epigenet, Dana Farber Canc Inst, Boston, MA 02215 USA.
[Muhle-Goll, Claudia; Jung, Nicole; Luy, Burkhard; Braese, Stefan] Karlsruhe Inst Technol, Inst Organ Chem, D-76131 Karlsruhe, Germany.
[Smith, Emmanuel W.; Chen, Yu] Univ S Florida, Coll Med, Dept Mol Med, Tampa, FL 33612 USA.
[Buzon, Victor; Carbo, Laia R.; Estebanez-Perpina, Eva] Univ Barcelona, Inst Biomed, Dept Biochem & Mol Biol, Barcelona 08028, Spain.
[Schmitz, Katja] Tech Univ Darmstadt, Clemens Schopf Inst Organ Chem & Biochem, D-64287 Darmstadt, Germany.
[Fruk, Ljiljana] Karlsruhe Inst Technol, Deutsch Forschungsgemeinschaft Ctr Nanostruct, D-76131 Karlsruhe, Germany.
[Cox, Marc B.] Univ Texas El Paso, Border Biomed Res Ctr, El Paso, TX 79968 USA.
[Cox, Marc B.] Univ Texas El Paso, Dept Biol Sci, El Paso, TX 79968 USA.
RP Cato, ACB (reprint author), Karlsruhe Inst Technol, Inst Toxicol & Genet, D-76344 Eggenstein Leopoldshafen, Germany.
EM andrew.cato@kit.edu
RI Braese, Stefan/B-9057-2008; Cato, Andrew/H-2071-2013; Schmitz,
Katja/B-9342-2008;
OI Braese, Stefan/0000-0003-4845-3191; Cato, Andrew/0000-0001-8508-3834;
Schmitz, Katja/0000-0001-9023-318X; Fruk, Ljiljana/0000-0003-2104-5817;
Brown, Myles/0000-0002-8213-1658
FU National Institutes of Health from the National Center for Research
Resources [5 G12 RR008124]; National Institutes of Health from the
National Institute on Minority Health and Health Disparities [8 G12
MD007592]; National Institutes of Health [1P01CA163227-01A1,
P50CA090381]; KIT start-up funds; Deutsche Krebshilfe [110237]; Cancer
Prevention and Research Institute of Texas [RP110444-P2]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants 5 G12 RR008124 (from the National Center for Research
Resources) and 8 G12 MD007592 (from the National Institute on Minority
Health and Health Disparities) (to M. B. C.) and 1P01CA163227-01A1
(Androgen Receptor Action in Castration Resistant Prostate Cancer) and
P50CA090381 (Prostate Cancer SPORE) (to M. B.). This work was also
supported by grants from the KIT start-up funds and Deutsche Krebshilfe
Grant 110237 (to A. C. B. C.) and Cancer Prevention and Research
Institute of Texas Grant RP110444-P2 (to M. B. C.).
NR 71
TC 18
Z9 18
U1 1
U2 15
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 28
PY 2014
VL 289
IS 13
BP 8839
EP 8851
DI 10.1074/jbc.M113.534859
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AD7UJ
UT WOS:000333472100010
PM 24523409
ER
PT J
AU Baek, JI
Choi, SY
Chacon-Heszele, MF
Zuo, XF
Lipschutz, JH
AF Baek, Jeong-In
Choi, Soo Young
Chacon-Heszele, Maria F.
Zuo, Xiaofeng
Lipschutz, Joshua H.
TI Expression of Drosophila forkhead transcription factors during kidney
development
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Drosophila forkhead; Transcription factor; Nephrogenesis
ID DISRUPTION; FAMILY; BF-2
AB The Drosophila forkhead (Dfkh) family of transcription factors has over 40 family members. One Dfkh family member, BF2 (aka FoxD1), has been shown, by targeted disruption, to be essential for kidney development. In order to determine if other Dfkh family members were involved in kidney development and to search for new members of this family, reverse transcriptase polymerase chain reaction (RT-PCR) was performed using degenerate primers of the consensus sequence of the DNA binding domain of this family and developing rat kidney RNA. The RT-PCR product was used to probe RNA from a developing rat kidney (neonatal), from a 20-day old kidney, and from an adult kidney. The RT-PCR product hybridized only to a developing kidney RNA transcript of similar to 2.3 kb (the size of BF2). A lambda gt10 mouse neonatal kidney library was then screened, using the above-described RT-PCR product as a probe. Three lambda phage clones were isolated that strongly hybridized to the RT-PCR probe. Sequencing of the RT-PCR product and the lambda phage clones isolated from the developing kidney library revealed Dfkh BF2. In summary, only MI6 family member BF2, which has already been shown to be essential for nephrogenesis, was identified in our screen and no other candidate Dfkh family members were identified. Published by Elsevier Inc.
C1 [Baek, Jeong-In; Choi, Soo Young; Chacon-Heszele, Maria F.; Zuo, Xiaofeng; Lipschutz, Joshua H.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Baek, Jeong-In; Choi, Soo Young; Chacon-Heszele, Maria F.; Zuo, Xiaofeng; Lipschutz, Joshua H.] VAMC, Philadelphia, PA 19104 USA.
[Lipschutz, Joshua H.] Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA 19104 USA.
RP Lipschutz, JH (reprint author), Room 405C,Clin Res Bldg,415 Curie Blvd, Philadelphia, PA 19104 USA.
EM jhlipsch@mail.med.upenn.edu
FU Veteran Affairs; NIH [RO1 DK069909, DK047757]; NephHope Foundation
FX This work was supported in part by the Veteran Affairs (Merit Award to
J.H.L.), the NIH (RO1 DK069909 and DK047757 to J.H.L.), and the NephHope
Foundation (Fellowship award to M.F.C.H.).
NR 7
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
EI 1090-2104
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD MAR 28
PY 2014
VL 446
IS 1
BP 15
EP 17
DI 10.1016/j.bbrc.2014.01.135
PG 3
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA AF4AX
UT WOS:000334654900003
PM 24491558
ER
PT J
AU Tjokro, NO
Rocco, CJ
Priyadarshini, R
Davey, ME
Goodman, SD
AF Tjokro, Natalia O.
Rocco, Christopher J.
Priyadarshini, Richa
Davey, Mary E.
Goodman, Steven D.
TI A Biochemical Analysis of the Interaction of Porphyromonas gingivalis HU
PG0121 Protein with DNA
SO PLOS ONE
LA English
DT Article
ID 6 CAPSULAR SEROTYPES; ESCHERICHIA-COLI HU; BINDING PROTEIN; CRUCIFORM
DNA; HIGH-AFFINITY; BACILLUS-SUBTILIS; STRANDED-DNA; TRANSCRIPTION;
GENE; BACTERIA
AB K-antigen capsule, a key virulence determinant of the oral pathogen Porphyromonas gingivalis, is synthesized by proteins encoded in a series of genes transcribed as a large polycistronic message. Previously, we identified a 77-base pair inverted repeat region with the potential to form a large stem-loop structure at the 5' end of this locus. PG0121, one of two genes flanking the capsule operon, was found to be co-transcribed with the operon and to share high similarity to the DNA binding protein HU from Escherichia coli. A null mutation in PG0121 results in down-regulation of transcription of the capsule synthesis genes and production of capsule. Furthermore, we have also shown that PG0121 gene can complement multiple deficiencies in a strain of E. coli that is deficient for both the alpha and beta subunits of HU. Here, we examined the biochemical properties of the interaction of PG0121 to DNA with the emphasis on the kinds of nucleic acid architectures that may be encountered at the 77-bp inverted repeat. We have concluded that although some DNA binding characteristics are shared with E. coli HU, HU PG0121 also shows some distinct characteristics that set it apart from other HU-like proteins tested to date. We discuss our results in the context of how PG0121 may affect the regulation of the K-antigen capsule expression.
C1 [Tjokro, Natalia O.] Univ So Calif, Dept Mol & Computat Biol, Los Angeles, CA USA.
[Priyadarshini, Richa; Davey, Mary E.] Forsyth Inst, Dept Mol Genet, Boston, MA USA.
[Rocco, Christopher J.; Goodman, Steven D.] Nationwide Childrens Hosp, Ctr Microbial Pathogenesis, Res Inst, Columbus, OH USA.
RP Davey, ME (reprint author), Univ Florida, Coll Dent, Dept Oral Biol, Gainesville, FL 32610 USA.
EM mdavey@dental.ufl.edu; steven.goodman@nationwidechildrens.org
RI Goodman, Steven/C-5732-2013
FU National Institutes of Health [5R01DE019117-06]
FX This work was supported by National Institutes of Health grant
5R01DE019117-06 (NIH; www.nih.gov) to MED and SDG. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 62
TC 4
Z9 4
U1 2
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 28
PY 2014
VL 9
IS 3
AR e93266
DI 10.1371/journal.pone.0093266
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE0TC
UT WOS:000333678100037
PM 24681691
ER
PT J
AU Lee, S
Vinegoni, C
Sebas, M
Weissleder, R
AF Lee, Sungon
Vinegoni, Claudio
Sebas, Matthew
Weissleder, Ralph
TI Automated motion artifact removal for intravital microscopy, without a
priori information
SO SCIENTIFIC REPORTS
LA English
DT Article
ID VIVO; RESOLUTION; ANIMALS; HEART
AB Intravital fluorescence microscopy, through extended penetration depth and imaging resolution, provides the ability to image at cellular and subcellular resolution in live animals, presenting an opportunity for new insights into in vivo biology. Unfortunately, physiological induced motion components due to respiration and cardiac activity are major sources of image artifacts and impose severe limitations on the effective imaging resolution that can be ultimately achieved in vivo. Here we present a novel imaging methodology capable of automatically removing motion artifacts during intravital microscopy imaging of organs and orthotopic tumors. The method is universally applicable to different laser scanning modalities including confocal and multiphoton microscopy, and offers artifact free reconstructions independent of the physiological motion source and imaged organ. The methodology, which is based on raw data acquisition followed by image processing, is here demonstrated for both cardiac and respiratory motion compensation in mice heart, kidney, liver, pancreas and dorsal window chamber.
C1 [Lee, Sungon; Vinegoni, Claudio; Sebas, Matthew; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Lee, Sungon; Vinegoni, Claudio; Sebas, Matthew; Weissleder, Ralph] Harvard Univ, Sch Med, Richard B Simches Res Ctr, Boston, MA 02114 USA.
[Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
[Lee, Sungon] Korea Inst Sci & Technol, Interact & Robot Res Ctr, Seoul, South Korea.
RP Vinegoni, C (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA.
EM cvinegoni@mgh.harvard.edu
FU National Heart, Lung, and Blood Institute, National Institutes of
Health, Department of Health and Human Services [HHSN268201000044C];
Institute of Biomedical Engineering [R01EB006432]; NIH HHS/United States
[P01 CA139980/CA/NCI, 1R01CA164448/CA/NCI]; KIST Institutional Program
[2Z04010]
FX This project was funded in part by Federal funds from the National
Heart, Lung, and Blood Institute, National Institutes of Health,
Department of Health and Human Services (under Contract No.
HHSN268201000044C), and from the Institute of Biomedical Engineering
(under R01EB006432), P01 CA139980/CA/NCI NIH HHS/United States,
1R01CA164448/CA/NCI NIH HHS/United States and the KIST Institutional
Program (Project No. 2Z04010).
NR 23
TC 8
Z9 8
U1 2
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD MAR 28
PY 2014
VL 4
AR 4507
DI 10.1038/srep04507
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD8KU
UT WOS:000333515700014
PM 24676021
ER
PT J
AU Hayano, K
Fuentes-Orrego, JM
Sahani, DV
AF Hayano, Koichi
Fuentes-Orrego, Jorge M.
Sahani, Dushyant V.
TI New approaches for precise response evaluation in hepatocellular
carcinoma
SO WORLD JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
DE Hepatocellular carcinoma; World Health Organization criteria; Response
Evaluation Criteria in Solid Tumors; European Association for the Study
of Liver; Computed tomography perfusion; Dynamic
contrast-enhanced-magnetic resonance imaging; Diffusion-weighted
imaging; Positron emission tomography
ID POSITRON-EMISSION-TOMOGRAPHY; APPARENT DIFFUSION-COEFFICIENT;
TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION; RESONANCE-IMAGING BIOMARKERS;
SOLID TUMORS RECIST; CELL LUNG-CANCER; COMPUTED-TOMOGRAPHY; EVALUATION
CRITERIA; LIVER-TUMORS; COLORECTAL-CANCER
AB With the increasing clinical use of cytostatic and novel biologic targeted agents, conventional morphologic tumor burden assessments, including World Health Organization criteria and Response Evaluation Criteria in Solid Tumors, are confronting limitations because of their difficulties in distinguishing viable tumor from necrotic or fibrotic tissue. Therefore, the investigation for reliable quantitative biomarkers of therapeutic response such as metabolic imaging or functional imaging has been desired. In this review, we will discuss the conventional and new approaches to assess tumor burden. Since targeted therapy or locoregional therapies can induce biological changes much earlier than morphological changes, these functional tumor burden analyses are very promising. However, some of them have not gone thorough all steps for standardization and validation. Nevertheless, these new techniques and criteria will play an important role in the cancer management, and provide each patient more tailored therapy. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.
C1 [Hayano, Koichi; Fuentes-Orrego, Jorge M.; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA.
RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA.
EM dsahani@partners.org
OI Fuentes-Orrego, Jorge/0000-0002-9254-0746
NR 80
TC 2
Z9 2
U1 1
U2 6
PU BAISHIDENG PUBL GRP CO LTD
PI WANCHAI
PA ROOM 1701, 17-F, HENAN BUILDING, NO. 90, JAFFE RD, WANCHAI, HONG KONG
100025, PEOPLES R CHINA
SN 1007-9327
EI 2219-2840
J9 WORLD J GASTROENTERO
JI World J. Gastroenterol.
PD MAR 28
PY 2014
VL 20
IS 12
BP 3059
EP 3068
DI 10.3748/wjg.v20.i12.3059
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AE0PH
UT WOS:000333667700001
PM 24696594
ER
PT J
AU Bhagwat, N
Koppikar, P
Keller, M
Marubayashi, S
Shank, K
Rampal, R
Qi, J
Kleppe, M
Patel, HJ
Shah, SK
Taldone, T
Bradner, JE
Chiosis, G
Levine, RL
AF Bhagwat, Neha
Koppikar, Priya
Keller, Matthew
Marubayashi, Sachie
Shank, Kaitlyn
Rampal, Raajit
Qi, Jun
Kleppe, Maria
Patel, Hardik J.
Shah, Smit K.
Taldone, Tony
Bradner, James E.
Chiosis, Gabriela
Levine, Ross L.
TI Improved targeting of JAK2 leads to increased therapeutic efficacy in
myeloproliferative neoplasms
SO BLOOD
LA English
DT Article
ID TYROSINE KINASE JAK2; ACTIVATING MUTATION; MYELOID METAPLASIA;
POLYCYTHEMIA-VERA; MYELOFIBROSIS; RESISTANCE; INHIBITORS; DISORDERS;
JAK2V617F; DOMAIN
AB The discovery of JAK2/MPL mutations in patients with myeloproliferative neoplasms (MPN) led to clinical development of Janus kinase (JAK) inhibitors for treatment of MPN. These inhibitors improve constitutional symptoms and splenomegaly but do not significantly reduce mutant allele burden in patients. We recently showed that chronic exposure to JAK inhibitors results in inhibitor persistence via JAK2 transactivation and persistent JAK-signal transducer and activator of transcription signaling. We performed genetic and pharmacologic studies to determine whether improved JAK2 inhibition would show increased efficacy in MPN models and primary samples. Jak2 deletion in vivo led to profound reduction in disease burden not seen with JAK inhibitors, and deletion of Jak2 following chronic ruxolitinib therapy markedly reduced mutant allele burden. This demonstrates that JAK2 remains an essential target in MPN cells that survive in the setting of chronic JAK inhibition. Combination therapy with the heat shock protein 90 (HSP90) inhibitor PU-H71 and ruxolitinib reduced total and phospho-JAK2 and achieved more potent inhibition of downstream signaling than ruxolitinib monotherapy. Combination treatment improved blood counts, spleen weights, and reduced bone marrow fibrosis compared with ruxolitinib alone. These data suggest alternate approaches that increase JAK2 targeting, including combination JAK/HSP90 inhibitor therapy, are warranted in the clinical setting.
C1 [Bhagwat, Neha; Koppikar, Priya; Keller, Matthew; Marubayashi, Sachie; Shank, Kaitlyn; Rampal, Raajit; Kleppe, Maria; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
[Bhagwat, Neha; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Gerstner Sloan Kettering Grad Sch Biomed Sci, New York, NY 10065 USA.
[Rampal, Raajit] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
[Qi, Jun; Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Patel, Hardik J.; Shah, Smit K.; Taldone, Tony; Chiosis, Gabriela] Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Chem Program, New York, NY 10065 USA.
[Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Leukemia Serv, New York, NY 10065 USA.
RP Levine, RL (reprint author), Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, 1275 York Ave,Box 20, New York, NY 10065 USA.
EM leviner@mskcc.org
FU Leukemia & Lymphoma Society Translational Research Program grant;
National Cancer Institute at the National Institutes of Health
[1R01CA151949-01]; Geoffrey Beene Cancer Research Center; EMBO
FX This work was supported by a Leukemia & Lymphoma Society Translational
Research Program grant (R. L. L. and G. C.) and by National Cancer
Institute at the National Institutes of Health grants 1R01CA151949-01
(R. L. L.). R. L. L. and R. R. are also supported by grants from the
Geoffrey Beene Cancer Research Center.; M. Kleppe is a fellow of the
Leukemia & Lymphoma Society and was previously supported by an EMBO
Postdoctoral Fellowship. R. L. L. is a Leukemia & Lymphoma Society
Scholar.
NR 22
TC 29
Z9 29
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAR 27
PY 2014
VL 123
IS 13
BP 2075
EP 2083
DI 10.1182/blood-2014-01-547760
PG 9
WC Hematology
SC Hematology
GA AH1AP
UT WOS:000335852200020
PM 24470592
ER
PT J
AU Scadden, DT
AF Scadden, David T.
TI Nice Neighborhood: Emerging Concepts of the Stem Cell Niche
SO CELL
LA English
DT Review
ID BONE-MARROW MICROENVIRONMENT; HEMATOPOIETIC STEM; IN-VIVO; PROGENITOR
CELLS; ENDOTHELIAL-CELLS; MAINTENANCE; REGENERATION; FATE; ENGRAFTMENT;
DROSOPHILA
AB No metazoan cell survives on its own, absent the signals and support of its milieu. For multicellular life with specialized tissues to persist, organization is everything and so defining the association of position with cell state is critical to understanding how tissues function, maintain, and repair. This review focuses specifically on place for progenitor and stem cells. Especially emphasized are hematopoietic cells that balance free movement and stable position and where concepts of regulatory interrelationships have been shown with some precision. It reviews classical and emerging concepts of the niche, particularly considering how niche functions may participate in neoplastic disease.
C1 [Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
RP Scadden, DT (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
EM david_scadden@harvard.edu
FU Gerald and Darlene Jordan Chair; [HL096372]; [CA148180]
FX The contributions of Elizabeth Scadden, Jay Rajagopal, Rushdia Yusuf,
Vionnie Yu, Borja Saez, and Jonathon Hoggatt are gratefully acknowledged
for their thoughtful input, editing, and help with figures. Members of
the Scadden lab have been invaluable in shaping this work and being the
best partners in discovery a lab chief could ever imagine. There is much
outstanding work in the field that is not included in this piece for
reasons of space, and I ask the forbearance of my colleagues for
omissions of their contributions. This work was funded by: HL096372,
CA148180, and the Gerald and Darlene Jordan Chair.
NR 70
TC 79
Z9 82
U1 6
U2 40
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD MAR 27
PY 2014
VL 157
IS 1
BP 41
EP 50
DI 10.1016/j.cell.2014.02.013
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AE4QW
UT WOS:000333968900006
PM 24679525
ER
PT J
AU Rajabi, H
Alam, M
Takahashi, H
Kharbanda, A
Guha, M
Ahmad, R
Kufe, D
AF Rajabi, H.
Alam, M.
Takahashi, H.
Kharbanda, A.
Guha, M.
Ahmad, R.
Kufe, D.
TI MUC1-C oncoprotein activates the ZEB1/miR-200c regulatory loop and
epithelial-mesenchymal transition
SO ONCOGENE
LA English
DT Article
DE MUC1-C; ZEB1; miR-200c; breast cancer; EMT
ID BREAST-CANCER CELLS; FACTOR-KAPPA-B; TRANSCRIPTION FACTOR;
DOWN-REGULATION; FEEDBACK LOOP; STEM-CELLS; E-CADHERIN; ZEB1;
METASTASIS; FAMILY
AB The epithelial-mesenchymal transition (EMT) is activated in cancer cells by ZEB1, a member of the zinc finger/homeodomain family of transcriptional repressors. The mucin 1 (MUC1) heterodimeric protein is aberrantly overexpressed in human carcinoma cells. The present studies in breast cancer cells demonstrate that the oncogenic MUC1-C subunit induces expression of ZEB1 by a NF-kappa B (nuclear factor kappa B) p65-dependent mechanism. MUC1-C occupies the ZEB1 promoter with NF-kappa B p65 and thereby promotes ZEB1 transcription. In turn, ZEB1 associates with MUC1-C and the ZEB1/MUC1-C complex contributes to the transcriptional suppression of miR-200c, an inducer of epithelial differentiation. The co-ordinate upregulation of ZEB1 and suppression of miR-200c has been linked to the induction of EMT. In concert with the effects of MUC1-C on ZEB1 and miR-200c, we show that MUC1-C induces EMT and cellular invasion by a ZEB1-mediated mechanism. These findings indicate that (i) MUC1-C activates ZEB1 and suppresses miR-200c with the induction of EMT and (ii) targeting MUC1-C could be an effective approach for the treatment of breast and possibly other types of cancers that develop EMT properties.
C1 [Rajabi, H.; Alam, M.; Takahashi, H.; Kharbanda, A.; Guha, M.; Ahmad, R.; Kufe, D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA.
RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave,Dana 830, Boston, MA 02215 USA.
EM donald_kufe@dfci.harvard.edu
FU National Cancer Institute of the National Institutes of Health [CA97098,
CA166480]
FX Research reported in this publication was supported by the National
Cancer Institute of the National Institutes of Health under award
numbers CA97098 and CA166480.
NR 37
TC 21
Z9 22
U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD MAR 27
PY 2014
VL 33
IS 13
BP 1680
EP 1689
DI 10.1038/onc.2013.114
PG 10
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA AE9QY
UT WOS:000334344700008
PM 23584475
ER
PT J
AU Grayson, AR
Walsh, EM
Cameron, MJ
Godec, J
Ashworth, T
Ambrose, JM
Aserlind, AB
Wang, H
Evan, GI
Kluk, MJ
Bradner, JE
Aster, JC
French, CA
AF Grayson, A. R.
Walsh, E. M.
Cameron, M. J.
Godec, J.
Ashworth, T.
Ambrose, J. M.
Aserlind, A. B.
Wang, H.
Evan, G. I.
Kluk, M. J.
Bradner, J. E.
Aster, J. C.
French, C. A.
TI MYC, a downstream target of BRD-NUT, is necessary and sufficient for the
blockade of differentiation in NUT midline carcinoma
SO ONCOGENE
LA English
DT Article
DE BRD4; NUT; MYC; epigenetic; differentiation; fusion oncogene
ID SQUAMOUS-CELL CARCINOMA; SET ENRICHMENT ANALYSIS; C-MYC; POOR-PROGNOSIS;
IN-VIVO; INDUCED APOPTOSIS; BET BROMODOMAINS; STEM-CELLS; GENE;
REARRANGEMENT
AB NUT midline carcinoma (NMC) is an aggressive type of squamous cell carcinoma that is defined by the presence of BRD-NUT fusion oncogenes, which encode chimeric proteins that block differentiation and maintain tumor growth. BRD-NUT oncoproteins contain two bromodomains whose binding to acetylated histones is required for the blockade of differentiation in NMC, but the mechanisms by which BRD-NUT act remain uncertain. Here, we provide evidence that MYC is a key downstream target of BRD4-NUT. Expression profiling of NMCs shows that the set of genes whose expression is maintained by BRD4-NUT is highly enriched for MYC upregulated genes, and MYC and BRD4-NUT protein expression is strongly correlated in primary NMCs. More directly, we find that BRD4-NUT associates with the MYC promoter and is required to maintain MYC expression in NMC cell lines. Moreover, both siRNA knockdown of MYC and a dominant-negative form of MYC, omomyc, induce differentiation of NMC cells. Conversely, differentiation of NMC cells induced by knockdown of BRD4-NUT is abrogated by enforced expression of MYC. Together, these findings suggest that MYC is a downstream target of BRD4-NUT that is required for maintenance of NMC cells in an undifferentiated, proliferative state. Our findings support a model in which dysregulation of MYC by BRD-NUT fusion proteins has a central role in the pathogenesis of NMC.
C1 [Grayson, A. R.; Walsh, E. M.; Cameron, M. J.; Ashworth, T.; Ambrose, J. M.; Aserlind, A. B.; Wang, H.; Kluk, M. J.; Aster, J. C.; French, C. A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Grayson, A. R.; Walsh, E. M.; Cameron, M. J.; Ashworth, T.; Ambrose, J. M.; Aserlind, A. B.; Wang, H.; Kluk, M. J.; Bradner, J. E.; Aster, J. C.; French, C. A.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Godec, J.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
[Godec, J.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Evan, G. I.] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England.
[Bradner, J. E.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
RP French, CA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
EM cfrench@partners.org
FU Samuel Waxman Cancer Research Foundation; US National Institutes of
Health [1R01CA124633]; Adolescent and Young Adult Gap Fund; American
Association for Cancer Research [10-20-03-FREN]
FX This work was supported by the Samuel Waxman Cancer Research Foundation
(CAF and JEB), the US National Institutes of Health grant 1R01CA124633
(CAF), the Adolescent and Young Adult Gap Fund (CAF and JEB), and the
American Association for Cancer Research grant 10-20-03-FREN. We would
like to thank Dr Nicholas Haining for assistance with GSEA. Many thanks
to Dr Paola Dal Cin for providing fluorescent in situ hybridization
probes, and to Mr Dan Shea for his assistance with fluorescent in situ
hybridization photomicrographs. High-throughput siRNA assays were
performed at the Institute of Chemistry and Cell Biology, Longwood
Campus (ICCB-L, http://iccb.med.harvard.edu/).
NR 45
TC 30
Z9 30
U1 2
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD MAR 27
PY 2014
VL 33
IS 13
BP 1736
EP 1742
DI 10.1038/onc.2013.126
PG 7
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA AE9QY
UT WOS:000334344700013
PM 23604113
ER
PT J
AU Cranmer, HH
Biddinger, PD
AF Cranmer, Hilarie H.
Biddinger, Paul D.
TI Typhoon Haiyan and the Professionalization of Disaster Response
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
AB When international medical response teams landed in the Philippines after Typhoon Haiyan, they had to act as professional humanitarian responders. Medical responders to disasters can help best when they are well prepared and function as part of a coordinated effort. When international medical response teams landed in the Philippines last November in the days and weeks after Super Typhoon Haiyan hit, it was immediately apparent that they needed to act as professional humanitarian responders. The top priority was not that they deploy their medical skills but that they support the plans that were already in place. Although there were posters directing foreign medical response teams to register with the Philippine government, the trucks loaded with bags of rice from the World Food Program being delivered to the Department of Social Welfare and Development should have tipped off the response teams ...
C1 [Cranmer, Hilarie H.; Biddinger, Paul D.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Cranmer, Hilarie H.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA.
[Biddinger, Paul D.] Harvard Univ, Sch Publ Hlth, Div Policy Translat & Leadership Dev, Boston, MA 02115 USA.
RP Cranmer, HH (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
NR 4
TC 6
Z9 6
U1 4
U2 25
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 27
PY 2014
VL 370
IS 13
BP 1185
EP 1187
DI 10.1056/NEJMp1401820
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA AD7EW
UT WOS:000333426000005
PM 24552286
ER
PT J
AU Shaw, AT
Kim, DW
Mehra, R
Tan, DSW
Felip, E
Chow, LQM
Camidge, DR
Vansteenkiste, J
Sharma, S
De Pas, T
Riely, GJ
Solomon, BJ
Wolf, J
Thomas, M
Schuler, M
Liu, G
Santoro, A
Lau, YY
Goldwasser, M
Boral, AL
Engelman, JA
AF Shaw, Alice T.
Kim, Dong-Wan
Mehra, Ranee
Tan, Daniel S. W.
Felip, Enriqueta
Chow, Laura Q. M.
Camidge, D. Ross
Vansteenkiste, Johan
Sharma, Sunil
De Pas, Tommaso
Riely, Gregory J.
Solomon, Benjamin J.
Wolf, Juergen
Thomas, Michael
Schuler, Martin
Liu, Geoffrey
Santoro, Armando
Lau, Yvonne Y.
Goldwasser, Meredith
Boral, Anthony L.
Engelman, Jeffrey A.
TI Ceritinib in ALK-Rearranged Non-Small-Cell Lung Cancer
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID EML4-ALK FUSION GENE; KINASE INHIBITOR; ACQUIRED-RESISTANCE; CLINICAL
RESISTANCE; MUTATION; EGFR; CRIZOTINIB; GEFITINIB; STI-571; TRIALS
AB BackgroundNon-small-cell lung cancer (NSCLC) harboring the anaplastic lymphoma kinase gene (ALK) rearrangement is sensitive to the ALK inhibitor crizotinib, but resistance invariably develops. Ceritinib (LDK378) is a new ALK inhibitor that has shown greater antitumor potency than crizotinib in preclinical studies.
MethodsIn this phase 1 study, we administered oral ceritinib in doses of 50 to 750 mg once daily to patients with advanced cancers harboring genetic alterations in ALK. In an expansion phase of the study, patients received the maximum tolerated dose. Patients were assessed to determine the safety, pharmacokinetic properties, and antitumor activity of ceritinib. Tumor biopsies were performed before ceritinib treatment to identify resistance mutations in ALK in a group of patients with NSCLC who had had disease progression during treatment with crizotinib.
ResultsA total of 59 patients were enrolled in the dose-escalation phase. The maximum tolerated dose of ceritinib was 750 mg once daily; dose-limiting toxic events included diarrhea, vomiting, dehydration, elevated aminotransferase levels, and hypophosphatemia. This phase was followed by an expansion phase, in which an additional 71 patients were treated, for a total of 130 patients overall. Among 114 patients with NSCLC who received at least 400 mg of ceritinib per day, the overall response rate was 58% (95% confidence interval [CI], 48 to 67). Among 80 patients who had received crizotinib previously, the response rate was 56% (95% CI, 45 to 67). Responses were observed in patients with various resistance mutations in ALK and in patients without detectable mutations. Among patients with NSCLC who received at least 400 mg of ceritinib per day, the median progression-free survival was 7.0 months (95% CI, 5.6 to 9.5).
ConclusionsCeritinib was highly active in patients with advanced, ALK-rearranged NSCLC, including those who had had disease progression during crizotinib treatment, regardless of the presence of resistance mutations in ALK. (Funded by Novartis Pharmaceuticals and others; ClinicalTrials.gov number, NCT01283516.)
Ceritinib is 20 times as potent as crizotinib at inhibiting anaplastic lymphoma kinase (ALK) in vitro. In patients, ceritinib produced antitumor responses in 56% of those who had resistance to crizotinib. Genetic alterations in the anaplastic lymphoma kinase gene (ALK) are implicated in the pathogenesis of several human cancers.(1) ALK can be aberrantly activated by mutation, gene amplification, or chromosomal rearrangement, leading to the expression of a potent oncogenic driver. In non-small-cell lung cancer (NSCLC), ALK rearrangement occurs in approximately 5% of cases.(2)-(8)ALK-rearranged tumors depend on ALK for growth and survival and show marked sensitivity to ALK inhibitors such as crizotinib. Among patients with advanced, ALK-rearranged NSCLC, crizotinib has been associated with response rates of approximately 60% across multiple studies and a median progression-free survival ...
C1 [Shaw, Alice T.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Kim, Dong-Wan] Seoul Natl Univ Hosp, Seoul 110744, South Korea.
[Mehra, Ranee] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Tan, Daniel S. W.] Natl Canc Ctr, Singapore, Singapore.
[Tan, Daniel S. W.] Genome Inst Singapore, Singapore, Singapore.
[Felip, Enriqueta] Vall dHebron Univ, Barcelona, Spain.
[Chow, Laura Q. M.] Univ Washington, Seattle, WA 98195 USA.
[Camidge, D. Ross] Univ Colorado, Denver, CO 80202 USA.
[Vansteenkiste, Johan] Univ Hosp KU Leuven, Louvain, Belgium.
[Sharma, Sunil] Huntsman Canc Inst, Salt Lake City, UT USA.
[De Pas, Tommaso] Ist Europeo Oncol, Milan, Italy.
[Santoro, Armando] Ist Clin Humanitas, Ist Ricovero & Cura Carattere Sci, Milan, Italy.
[Riely, Gregory J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Solomon, Benjamin J.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.
[Wolf, Juergen] Univ Hosp Cologne, Ctr Integrated Oncol, Cologne, Germany.
[Thomas, Michael] Heidelberg Univ, Thoraxklin, Translat Lung Res Ctr Heidelberg, German Ctr Lung Res, Heidelberg, Germany.
[Schuler, Martin] German Canc Consortium, Heidelberg, Germany.
[Schuler, Martin] Univ Duisburg Essen, Essen, Germany.
[Liu, Geoffrey] Princess Margaret Canc Ctr, Toronto, ON, Canada.
[Lau, Yvonne Y.; Goldwasser, Meredith; Boral, Anthony L.] Novartis Inst BioMed Res, Cambridge, MA USA.
RP Shaw, AT (reprint author), Massachusetts Gen Hosp, Ctr Canc, Yawkey 7B,32 Fruit St, Boston, MA 02114 USA.
EM ashaw1@mgh.harvard.edu
FU Novartis Pharmaceuticals; National Cancer Institute [5R01CA164273]; V
Foundation Translational Research Grant; Be a Piece of the Solution;
Evan Spirito Memorial Foundation
FX Supported by Novartis Pharmaceuticals, by a grant from the National
Cancer Institute (5R01CA164273, to Drs. Shaw and Engelman), by a V
Foundation Translational Research Grant (to Drs. Shaw and Engelman), by
Be a Piece of the Solution, and by the Evan Spirito Memorial Foundation.
NR 28
TC 462
Z9 494
U1 8
U2 95
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 27
PY 2014
VL 370
IS 13
BP 1189
EP 1197
DI 10.1056/NEJMoa1311107
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA AD7EW
UT WOS:000333426000006
PM 24670165
ER
PT J
AU Chiappa, V
Chang, CY
Sellas, MI
Pierce, VM
Kradin, RL
AF Chiappa, Victor
Chang, Connie Y.
Sellas, Monique I.
Pierce, Virginia M.
Kradin, Richard L.
TI Case 10-2014: A 45-Year- Old Man with a Rash
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
AB A 45-year-old man was admitted to the hospital because of diffuse, purple, blanching livedo and signs of severe sepsis. Three days earlier, he had been bitten by a dog. A diagnostic test result was received. Presentation of CaseDr. Douglas S. Micalizzi (Medicine): A 45-year-old man was admitted to this hospital because of a new rash. The patient had been well until 2 p.m. on the day before admission, when nausea, epigastric pain, and vomiting developed. The next morning, he was seen at another hospital, where he reported increasing asthma and right-sided back pain, which he rated at 10 on a scale of 0 to 10 (with 10 indicating the most severe pain). On examination, he was in moderate distress. The temperature was 36.5 degrees C, the blood pressure 112/69 mm Hg, the pulse 125 beats per ...
C1 [Chiappa, Victor] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Chang, Connie Y.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Sellas, Monique I.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Pierce, Virginia M.; Kradin, Richard L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Chiappa, Victor] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Chang, Connie Y.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Sellas, Monique I.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
[Pierce, Virginia M.; Kradin, Richard L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Chiappa, V (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
NR 4
TC 4
Z9 4
U1 0
U2 6
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 27
PY 2014
VL 370
IS 13
BP 1238
EP 1248
DI 10.1056/NEJMcpc1304162
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA AD7EW
UT WOS:000333426000012
PM 24670171
ER
PT J
AU Greka, A
Weins, A
Mundel, P
AF Greka, Anna
Weins, Astrid
Mundel, Peter
TI Abatacept in B7-1-Positive Proteinuric Kidney Disease Reply
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Greka, Anna; Mundel, Peter] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Weins, Astrid] Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Greka, A (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM mundel.peter@mgh.harvard.edu
FU NHLBI NIH HHS [R01 HL109582]; NIDDK NIH HHS [R01 DK062472, K01 DK068253,
K08 DK083511, K08 DK093783, P30 DK057521, R01 DK057683, R01 DK090316,
R01 DK095045, R01 DK099465, R56 DK093746]
NR 1
TC 2
Z9 2
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 27
PY 2014
VL 370
IS 13
BP 1263
EP 1266
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA AD7EW
UT WOS:000333426000021
PM 24670178
ER
PT J
AU Salado, IG
Redondo, M
Bello, ML
Perez, C
Liachko, NF
Kraemer, BC
Miguel, L
Lecourtois, M
Gil, C
Martinez, A
Perez, DI
AF Salado, Irene G.
Redondo, Miriam
Bello, Murilo L.
Perez, Concepcion
Liachko, Nicole F.
Kraemer, Brian C.
Miguel, Laetitia
Lecourtois, Magalie
Gil, Carmen
Martinez, Ana
Perez, Daniel I.
TI Protein Kinase CK-1 Inhibitors As New Potential Drugs for Amyotrophic
Lateral Sclerosis
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID FRONTOTEMPORAL LOBAR DEGENERATION; BLOOD-BRAIN-BARRIER; TDP-43
PROTEINOPATHIES; HEXANUCLEOTIDE REPEAT; MUTATIONS; ALS; PHOSPHORYLATION;
MODEL; OPTIMIZATION; EXPRESSION
AB Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease where motor neurons in cortex, brain stem, and spinal cord die progressively, resulting in muscle wasting, paralysis, and death. Currently, effective therapies for ALS are lacking; however, identification of pathological TAR DNA-binding protein 43 (TDP-43) as the hallmark lesion in sporadic ALS suggests new therapeutic targets for pharmacological intervention. Pathological TDP-43 phosphorylation appears to drive the onset and progression of ALS and may result from upregulation of the protein kinase CK-1 in affected neurons, resulting in postranslational TDP-43 modification. Consequently, brain penetrant specific CK-1 inhibitors may provide a new therapeutic strategy for treating ALS and other TDP-43 proteinopathies. Using a chemical genetic approach, we report the discovery and further optimization of a number of potent CK-1 delta inhibitors. Moreover, these small heterocyclic molecules are able to prevent TDP-43 phosphorylation in cell cultures, to increase Drosophila lifespan by reduction of TDP-43 neurotoxicity, and are predicted to cross the blood brain barrier. Thus, N-(benzothiazolyl)-2-phenyl-acetamides are valuable drug candidates for further studies and may be a new therapeutic approach for ALS and others pathologies in which TDP-43 is involved.
C1 [Salado, Irene G.; Redondo, Miriam; Bello, Murilo L.; Perez, Concepcion; Gil, Carmen; Martinez, Ana; Perez, Daniel I.] CSIC, Inst Quim Med, E-28006 Madrid, Spain.
[Bello, Murilo L.] Univ Fed Rio de Janeiro, Fac Farm, BR-21949900 Rio De Janeiro, Brazil.
[Liachko, Nicole F.; Kraemer, Brian C.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA.
[Liachko, Nicole F.; Kraemer, Brian C.] Univ Washington, Gerontol Div, Dept Med, Seattle, WA 98104 USA.
[Kraemer, Brian C.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Miguel, Laetitia; Lecourtois, Magalie] INSERM, U1079, F-76183 Rouen, France.
[Miguel, Laetitia; Lecourtois, Magalie] Univ Rouen, Normandie Univ, IRIB, F-76183 Rouen, France.
RP Martinez, A (reprint author), CSIC, Inst Quim Med, Juan Cierva 3, E-28006 Madrid, Spain.
EM amartinez@iqm.csic.es; dperez@iqm.csic.es
RI Gil, Carmen/J-8932-2014; Perez Fernandez, Daniel Ignacio/L-6245-2014;
Martinez, Ana/L-6414-2014; Perez, Concepcion/K-3684-2014
OI Gil, Carmen/0000-0002-3882-6081; Perez Fernandez, Daniel
Ignacio/0000-0003-1774-4471; Martinez, Ana/0000-0002-2707-8110;
FU MINECO [SAF2012-37979-C03-01]; Association Francaise contre les
Myopathies [AFM-16169]; Department of Veterans Affairs [1147891]; CDA2
[I01BX007080]; Ligue Europeenne Contre la Maladie d'Alzheimer (LECMA);
National Institutes of Health [R01NS064131]; MICINN (FPI program); CSIC
(JAE program); Coordenacao de Aperfeicoamento de Pessoal de Nivel
Superior (CAPES)
FX This work was supported by grants from MINECO (SAF2012-37979-C03-01 to
A.M.), Association Francaise contre les Myopathies (AFM-16169 to
D.I.P.), the Department of Veterans Affairs (Merit Review grant no.
1147891 to B.K.) and CDA2 no. I01BX007080 to N.L.), Ligue Europeenne
Contre la Maladie d'Alzheimer (LECMA to M.L.), and National Institutes
of Health (R01NS064131 to B.K.). I.G.S. and D.I.P. acknowledge a pre-
and postdoctoral fellowship from MICINN (FPI program) and CSIC (JAE
program), respectively. M.L.B. acknowledges a travel grant from
Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES). We
thank Elaine Loomis for outstanding technical assistance with
immunoblotting
NR 48
TC 9
Z9 9
U1 0
U2 18
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD MAR 27
PY 2014
VL 57
IS 6
BP 2755
EP 2772
DI 10.1021/jm500065f
PG 18
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA AD9IK
UT WOS:000333578400046
PM 24592867
ER
PT J
AU Lu, T
Aron, L
Zullo, J
Pan, Y
Kim, H
Chen, YW
Yang, TH
Kim, HM
Drake, D
Liu, XS
Bennett, DA
Colaiacovo, MP
Yankner, BA
AF Lu, Tao
Aron, Liviu
Zullo, Joseph
Pan, Ying
Kim, Haeyoung
Chen, Yiwen
Yang, Tun-Hsiang
Kim, Hyun-Min
Drake, Derek
Liu, X. Shirley
Bennett, David A.
Colaiacovo, Monica P.
Yankner, Bruce A.
TI REST and stress resistance in ageing and Alzheimer's disease
SO NATURE
LA English
DT Article
ID MILD COGNITIVE IMPAIRMENT; GENOME-WIDE ANALYSIS; CAENORHABDITIS-ELEGANS;
SEL-12 PRESENILIN; C. ELEGANS; LIFE-SPAN; PROTEIN; REPRESSOR; CHROMATIN;
NEURONS
AB Human neurons are functional over an entire lifetime, yet the mechanisms that preserve function and protect against neurodegeneration during ageing are unknown. Here we show that induction of the repressor element 1-silencing transcription factor (REST; also known as neuron-restrictive silencer factor, NRSF) is a universal feature of normal ageing in human cortical and hippocampal neurons. REST is lost, however, in mild cognitive impairment and Alzheimer's disease. Chromatin immunoprecipitation with deep sequencing and expression analysis show that REST represses genes that promote cell death and Alzheimer's disease pathology, and induces the expression of stress response genes. Moreover, REST potently protects neurons from oxidative stress and amyloid beta-protein toxicity, and conditional deletion of REST in the mouse brain leads to age-related neurodegeneration. A functional orthologue of REST, Caenorhabditis elegans SPR-4, also protects against oxidative stress and amyloid beta-protein toxicity. During normal ageing, REST is induced in part by cell non-autonomous Wnt signalling. However, in Alzheimer's disease, frontotemporal dementia and dementia with Lewy bodies, REST is lost from the nucleus and appears in autophagosomes together with pathological misfolded proteins. Finally, REST levels during ageing are closely correlated with cognitive preservation and longevity. Thus, the activation state of REST may distinguish neuroprotection from neurodegeneration in the ageing brain.
C1 [Lu, Tao; Aron, Liviu; Zullo, Joseph; Pan, Ying; Kim, Haeyoung; Yang, Tun-Hsiang; Kim, Hyun-Min; Drake, Derek; Colaiacovo, Monica P.; Yankner, Bruce A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Chen, Yiwen; Liu, X. Shirley] Dana Faber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Kim, Haeyoung; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.
RP Yankner, BA (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
EM Bruce_Yankner@hms.harvard.edu
RI Kim, Haeyoung/C-3069-2008
FU NIH [DP1OD006849, PO1AG27916, RO1AG26651, RO1GM072551, P30AG10161,
R01AG15819, R01AG17917]; Glenn Foundation for Medical Research
FX We thank members of the Yankner laboratory for suggestions and
discussion, Monlan Yuan, Allison Harwick, Kelly Dakin and Gregory Klein
for assistance, and Cheng Li and Dana Gabuzda for helpful discussion. We
also acknowledge the Rush Alzheimer's Disease Center, the Brigham and
Women's Hospital Brain Bank, the Massachusetts General Hospital ADRC
Brain Bank, and the Kathleen Price Bryan Brain Bank at Duke University
for providing tissue samples. This work was supported by an NIH
Director's Pioneer Award (DP1OD006849) and NIH grants PO1AG27916 and
RO1AG26651 to B.A.Y., RO1GM072551 to M. P. C., P30AG10161, R01AG15819
and R01AG17917 to D. A. B., and a grant from the Glenn Foundation for
Medical Research to B.A.Y. J.Z. is a Molecular Biology of
Neurodegeneration fellow at Harvard Medical School.
NR 55
TC 140
Z9 144
U1 19
U2 159
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 27
PY 2014
VL 507
IS 7493
BP 448
EP +
DI 10.1038/nature13163
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6WN
UT WOS:000333402000031
PM 24670762
ER
PT J
AU Forrest, ARR
Kawaji, H
Rehli, M
Baillie, JK
de Hoon, MJL
Haberle, V
Lassmann, T
Kulakovskiy, IV
Lizio, M
Itoh, M
Andersson, R
Mungall, CJ
Meehan, TF
Schmeier, S
Bertin, N
Jorgensen, M
Dimont, E
Arner, E
Schmidl, C
Schaefer, U
Medvedeva, YA
Plessy, C
Vitezic, M
Severin, J
Semple, CA
Ishizu, Y
Young, RS
Francescatto, M
Alam, I
Albanese, D
Altschuler, GM
Arakawa, T
Archer, JAC
Arner, P
Babina, M
Rennie, S
Balwierz, PJ
Beckhouse, AG
Pradhan-Bhatt, S
Blake, JA
Blumenthal, A
Bodega, B
Bonetti, A
Briggs, J
Brombacher, F
Burroughs, AM
Califano, A
Cannistraci, CV
Carbajo, D
Chen, Y
Chierici, M
Ciani, Y
Clevers, HC
Dalla, E
Davis, CA
Detmar, M
Diehl, AD
Dohi, T
Drablos, F
Edge, ASB
Edinger, M
Ekwall, K
Endoh, M
Enomoto, H
Fagiolini, M
Fairbairn, L
Fang, H
Farach-Carson, MC
Faulkner, GJ
Favorov, AV
Fisher, ME
Frith, MC
Fujita, R
Fukuda, S
Furlanello, C
Furuno, M
Furusawa, J
Geijtenbeek, TB
Gibson, AP
Gingeras, T
Goldowitz, D
Gough, J
Guhl, S
Guler, R
Gustincich, S
Ha, TJ
Hamaguchi, M
Hara, M
Harbers, M
Harshbarger, J
Hasegawa, A
Hasegawa, Y
Hashimoto, T
Herlyn, M
Hitchens, KJ
Sui, SJH
Hofmann, OM
Hoof, I
Hori, F
Huminiecki, L
Iida, K
Ikawa, T
Jankovic, BR
Jia, H
Joshi, A
Jurman, G
Kaczkowski, B
Kai, C
Kaida, K
Kaiho, A
Kajiyama, K
Kanamori-Katayama, M
Kasianov, A
Kasukawa, T
Katayama, S
Kato, S
Kawaguchi, S
Kawamoto, H
Kawamura, YI
Kawashima, T
Kempfle, JS
Kenna, TJ
Kere, J
Khachigian, LM
Kitamura, T
Klinken, SP
Knox, AJ
Kojima, M
Kojima, S
Kondo, N
Koseki, H
Koyasu, S
Krampitz, S
Kubosaki, A
Kwon, AT
Laros, JFJ
Lee, W
Lennartsson, A
Li, K
Lilje, B
Lipovich, L
Mackay-sim, A
Manabe, R
Mar, JC
Marchand, B
Mathelier, A
Mejhert, N
Meynert, A
Mizuno, Y
Morais, DAD
Morikawa, H
Morimoto, M
Moro, K
Motakis, E
Motohashi, H
Mummery, CL
Murata, M
Nagao-Sato, S
Nakachi, Y
Nakahara, F
Nakamura, T
Nakamura, Y
Nakazato, K
Van Nimwegen, E
Ninomiya, N
Nishiyori, H
Noma, S
Nozaki, T
Ogishima, S
Ohkura, N
Ohmiya, H
Ohno, H
Ohshima, M
Okada-Hatakeyama, M
Okazaki, Y
Orlando, V
Ovchinnikov, DA
Pain, A
Passier, R
Patrikakis, M
Persson, H
Piazza, S
Prendergast, JGD
Rackham, OJL
Ramilowski, JA
Rashid, M
Ravasi, T
Rizzu, P
Roncador, M
Roy, S
Rye, MB
Saijyo, E
Sajantila, A
Saka, A
Sakaguchi, S
Sakai, M
Sato, H
Satoh, H
Savvi, S
Saxena, A
Schneider, C
Schultes, EA
Schulze-Tanzil, GG
Schwegmann, A
Sengstag, T
Sheng, GJ
Shimoji, H
Shimoni, Y
Shin, JW
Simon, C
Sugiyama, D
Sugiyama, T
Suzuki, M
Suzuki, N
Swoboda, RK
't Hoen, PAC
Tagami, M
Takahashi, N
Takai, J
Tanaka, H
Tatsukawa, H
Tatum, Z
Thompson, M
Toyoda, H
Toyoda, T
Valen, E
van de Wetering, M
van den Berg, LM
Verardo, R
Vijayan, D
Vorontsov, IE
Wasserman, WW
Watanabe, S
Wells, CA
Winteringham, LN
Wolvetang, E
Wood, EJ
Yamaguchi, Y
Yamamoto, M
Yoneda, M
Yonekura, Y
Yoshida, S
Zabierowski, SE
Zhang, PG
Zhao, XB
Zucchelli, S
Summers, KM
Suzuki, H
Daub, CO
Kawai, J
Heutink, P
Hide, W
Freeman, TC
Lenhard, B
Bajic, VB
Taylor, MS
Makeev, VJ
Sandelin, A
Hume, DA
Carninci, P
Hayashizaki, Y
AF Forrest, Alistair R. R.
Kawaji, Hideya
Rehli, Michael
Baillie, J. Kenneth
de Hoon, Michiel J. L.
Haberle, Vanja
Lassmann, Timo
Kulakovskiy, Ivan V.
Lizio, Marina
Itoh, Masayoshi
Andersson, Robin
Mungall, Christopher J.
Meehan, Terrence F.
Schmeier, Sebastian
Bertin, Nicolas
Jorgensen, Mette
Dimont, Emmanuel
Arner, Erik
Schmidl, Christian
Schaefer, Ulf
Medvedeva, Yulia A.
Plessy, Charles
Vitezic, Morana
Severin, Jessica
Semple, Colin A.
Ishizu, Yuri
Young, Robert S.
Francescatto, Margherita
Alam, Intikhab
Albanese, Davide
Altschuler, Gabriel M.
Arakawa, Takahiro
Archer, John A. C.
Arner, Peter
Babina, Magda
Rennie, Sarah
Balwierz, Piotr J.
Beckhouse, Anthony G.
Pradhan-Bhatt, Swati
Blake, Judith A.
Blumenthal, Antje
Bodega, Beatrice
Bonetti, Alessandro
Briggs, James
Brombacher, Frank
Burroughs, A. Maxwell
Califano, Andrea
Cannistraci, Carlo V.
Carbajo, Daniel
Chen, Yun
Chierici, Marco
Ciani, Yari
Clevers, Hans C.
Dalla, Emiliano
Davis, Carrie A.
Detmar, Michael
Diehl, Alexander D.
Dohi, Taeko
Drablos, Finn
Edge, Albert S. B.
Edinger, Matthias
Ekwall, Karl
Endoh, Mitsuhiro
Enomoto, Hideki
Fagiolini, Michela
Fairbairn, Lynsey
Fang, Hai
Farach-Carson, Mary C.
Faulkner, Geoffrey J.
Favorov, Alexander V.
Fisher, Malcolm E.
Frith, Martin C.
Fujita, Rie
Fukuda, Shiro
Furlanello, Cesare
Furuno, Masaaki
Furusawa, Jun-ichi
Geijtenbeek, Teunis B.
Gibson, Andrew P.
Gingeras, Thomas
Goldowitz, Daniel
Gough, Julian
Guhl, Sven
Guler, Reto
Gustincich, Stefano
Ha, Thomas J.
Hamaguchi, Masahide
Hara, Mitsuko
Harbers, Matthias
Harshbarger, Jayson
Hasegawa, Akira
Hasegawa, Yuki
Hashimoto, Takehiro
Herlyn, Meenhard
Hitchens, Kelly J.
Sui, Shannan J. Ho
Hofmann, Oliver M.
Hoof, Ilka
Hori, Fumi
Huminiecki, Lukasz
Iida, Kei
Ikawa, Tomokatsu
Jankovic, Boris R.
Jia, Hui
Joshi, Anagha
Jurman, Giuseppe
Kaczkowski, Bogumil
Kai, Chieko
Kaida, Kaoru
Kaiho, Ai
Kajiyama, Kazuhiro
Kanamori-Katayama, Mutsumi
Kasianov, ArtemS.
Kasukawa, Takeya
Katayama, Shintaro
Kato, Sachi
Kawaguchi, Shuji
Kawamoto, Hiroshi
Kawamura, Yuki I.
Kawashima, Tsugumi
Kempfle, Judith S.
Kenna, Tony J.
Kere, Juha
Khachigian, Levon M.
Kitamura, Toshio
Klinken, S. Peter
Knox, Alan J.
Kojima, Miki
Kojima, Soichi
Kondo, Naoto
Koseki, Haruhiko
Koyasu, Shigeo
Krampitz, Sarah
Kubosaki, Atsutaka
Kwon, Andrew T.
Laros, Jeroen F. J.
Lee, Weonju
Lennartsson, Andreas
Li, Kang
Lilje, Berit
Lipovich, Leonard
Mackay-sim, Alan
Manabe, Ri-ichiroh
Mar, Jessica C.
Marchand, Benoit
Mathelier, Anthony
Mejhert, Niklas
Meynert, Alison
Mizuno, Yosuke
Morais, David A. de Lima
Morikawa, Hiromasa
Morimoto, Mitsuru
Moro, Kazuyo
Motakis, Efthymios
Motohashi, Hozumi
Mummery, Christine L.
Murata, Mitsuyoshi
Nagao-Sato, Sayaka
Nakachi, Yutaka
Nakahara, Fumio
Nakamura, Toshiyuki
Nakamura, Yukio
Nakazato, Kenichi
Van Nimwegen, Erik
Ninomiya, Noriko
Nishiyori, Hiromi
Noma, Shohei
Nozaki, Tadasuke
Ogishima, Soichi
Ohkura, Naganari
Ohmiya, Hiroko
Ohno, Hiroshi
Ohshima, Mitsuhiro
Okada-Hatakeyama, Mariko
Okazaki, Yasushi
Orlando, Valerio
Ovchinnikov, Dmitry A.
Pain, Arnab
Passier, Robert
Patrikakis, Margaret
Persson, Helena
Piazza, Silvano
Prendergast, James G. D.
Rackham, Owen J. L.
Ramilowski, Jordan A.
Rashid, Mamoon
Ravasi, Timothy
Rizzu, Patrizia
Roncador, Marco
Roy, Sugata
Rye, Morten B.
Saijyo, Eri
Sajantila, Antti
Saka, Akiko
Sakaguchi, Shimon
Sakai, Mizuho
Sato, Hiroki
Satoh, Hironori
Savvi, Suzana
Saxena, Alka
Schneider, Claudio
Schultes, Erik A.
Schulze-Tanzil, Gundula G.
Schwegmann, Anita
Sengstag, Thierry
Sheng, Guojun
Shimoji, Hisashi
Shimoni, Yishai
Shin, Jay W.
Simon, Christophe
Sugiyama, Daisuke
Sugiyama, Takaaki
Suzuki, Masanori
Suzuki, Naoko
Swoboda, Rolf K.
't Hoen, Peter A. C.
Tagami, Michihira
Takahashi, Naoko
Takai, Jun
Tanaka, Hiroshi
Tatsukawa, Hideki
Tatum, Zuotian
Thompson, Mark
Toyoda, Hiroo
Toyoda, Tetsuro
Valen, Eivind
van de Wetering, Marc
van den Berg, Linda M.
Verardo, Roberto
Vijayan, Dipti
Vorontsov, Ilya E.
Wasserman, Wyeth W.
Watanabe, Shoko
Wells, Christine A.
Winteringham, Louise N.
Wolvetang, Ernst
Wood, Emily J.
Yamaguchi, Yoko
Yamamoto, Masayuki
Yoneda, Misako
Yonekura, Yohei
Yoshida, Shigehiro
Zabierowski, Susan E.
Zhang, Peter G.
Zhao, Xiaobei
Zucchelli, Silvia
Summers, Kim M.
Suzuki, Harukazu
Daub, Carsten O.
Kawai, Jun
Heutink, Peter
Hide, Winston
Freeman, Tom C.
Lenhard, Boris
Bajic, Vladimir B.
Taylor, Martin S.
Makeev, Vsevolod J.
Sandelin, Albin
Hume, David A.
Carninci, Piero
Hayashizaki, Yoshihide
CA FANTOM Consortium
RIKEN PMI CLST DGT
TI A promoter-level mammalian expression atlas
SO NATURE
LA English
DT Article
ID HUMAN TRANSCRIPTION FACTORS; GENE-EXPRESSION; HOMEOBOX GENE; MICE
LACKING; HUMAN GENOME; INNER-EAR; DIFFERENTIATION; EVOLUTION; ONTOLOGY;
CELLS
AB Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly 'housekeeping', whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis revealskey transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.
C1 [Forrest, Alistair R. R.; Kawaji, Hideya; de Hoon, Michiel J. L.; Lassmann, Timo; Lizio, Marina; Itoh, Masayoshi; Bertin, Nicolas; Arner, Erik; Plessy, Charles; Vitezic, Morana; Severin, Jessica; Ishizu, Yuri; Arakawa, Takahiro; Bonetti, Alessandro; Burroughs, A. Maxwell; Fukuda, Shiro; Furuno, Masaaki; Harbers, Matthias; Harshbarger, Jayson; Hasegawa, Akira; Hasegawa, Yuki; Hashimoto, Takehiro; Hori, Fumi; Kaczkowski, Bogumil; Kaida, Kaoru; Kaiho, Ai; Kajiyama, Kazuhiro; Kanamori-Katayama, Mutsumi; Katayama, Shintaro; Kato, Sachi; Kawashima, Tsugumi; Kojima, Miki; Kondo, Naoto; Kubosaki, Atsutaka; Kwon, Andrew T.; Manabe, Ri-ichiroh; Motakis, Efthymios; Murata, Mitsuyoshi; Nagao-Sato, Sayaka; Nakazato, Kenichi; Ninomiya, Noriko; Nishiyori, Hiromi; Noma, Shohei; Ohmiya, Hiroko; Ramilowski, Jordan A.; Roy, Sugata; Saijyo, Eri; Saka, Akiko; Sakai, Mizuho; Saxena, Alka; Sengstag, Thierry; Shimoji, Hisashi; Shin, Jay W.; Simon, Christophe; Suzuki, Masanori; Suzuki, Naoko; Tagami, Michihira; Takahashi, Naoko; Watanabe, Shoko; Yoshida, Shigehiro; Suzuki, Harukazu; Daub, Carsten O.; Kawai, Jun; Carninci, Piero; Hayashizaki, Yoshihide] RIKEN, OSC, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
[Forrest, Alistair R. R.; Kawaji, Hideya; de Hoon, Michiel J. L.; Lassmann, Timo; Lizio, Marina; Itoh, Masayoshi; Bertin, Nicolas; Arner, Erik; Plessy, Charles; Severin, Jessica; Ishizu, Yuri; Arakawa, Takahiro; Bonetti, Alessandro; Furuno, Masaaki; Harshbarger, Jayson; Hasegawa, Akira; Hasegawa, Yuki; Hori, Fumi; Kaczkowski, Bogumil; Kaida, Kaoru; Kajiyama, Kazuhiro; Kasukawa, Takeya; Kato, Sachi; Kawashima, Tsugumi; Kojima, Miki; Kondo, Naoto; Kwon, Andrew T.; Manabe, Ri-ichiroh; Motakis, Efthymios; Murata, Mitsuyoshi; Nishiyori, Hiromi; Noma, Shohei; Ohmiya, Hiroko; Ramilowski, Jordan A.; Roy, Sugata; Sakai, Mizuho; Shin, Jay W.; Simon, Christophe; Suzuki, Naoko; Tagami, Michihira; Takahashi, Naoko; Yoshida, Shigehiro; Suzuki, Harukazu; Carninci, Piero] RIKEN, CLST, DGT, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
[Kawaji, Hideya; Itoh, Masayoshi; Kawai, Jun; Hayashizaki, Yoshihide] RIKEN, Prevent Med & Diag Innovat Program PMI, Wako, Saitama 3510198, Japan.
[Rehli, Michael; Schmidl, Christian; Edinger, Matthias] Univ Hosp Regensburg, Dept Internal Med 3, D-93042 Regensburg, Germany.
[Rehli, Michael; Edinger, Matthias] Regensburg Ctr Intervent Immunol RCI, D-93042 Regensburg, Germany.
[Baillie, J. Kenneth; Fairbairn, Lynsey; Fisher, Malcolm E.; Joshi, Anagha; Summers, Kim M.; Freeman, Tom C.; Hume, David A.] Univ Edinburgh, Roslin Inst, Edinburgh EH25 9RG, Midlothian, Scotland.
[Baillie, J. Kenneth; Fairbairn, Lynsey; Fisher, Malcolm E.; Joshi, Anagha; Summers, Kim M.; Freeman, Tom C.; Hume, David A.] Univ Edinburgh, Royal Dick Sch Vet Studies, Edinburgh EH25 9RG, Midlothian, Scotland.
[Haberle, Vanja] Univ Bergen, Dept Biol, NO-5006 Bergen, Norway.
[Haberle, Vanja; Lenhard, Boris] Univ London Imperial Coll Sci Technol & Med, Fac Med, Inst Clin Sci, MRC Clin Sci Ctr, London W12 0NN, England.
[Kulakovskiy, Ivan V.; Makeev, Vsevolod J.] Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow 119991, Russia.
[Kulakovskiy, Ivan V.; Medvedeva, Yulia A.; Favorov, Alexander V.; Kasianov, ArtemS.; Vorontsov, Ilya E.; Makeev, Vsevolod J.] Russian Acad Sci, Vavilov Inst Gen Genet, Moscow 119991, Russia.
[Andersson, Robin; Jorgensen, Mette; Chen, Yun; Hoof, Ilka; Li, Kang; Lilje, Berit; Zhao, Xiaobei; Sandelin, Albin] Univ Copenhagen, Bioinformat Ctr, Dept Biol, DK-2200 Copenhagen, Denmark.
[Andersson, Robin; Jorgensen, Mette; Chen, Yun; Hoof, Ilka; Li, Kang; Lilje, Berit; Zhao, Xiaobei; Sandelin, Albin] Univ Copenhagen, BRIC, DK-2200 Copenhagen, Denmark.
[Mungall, Christopher J.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Genom Div, Berkeley, CA 94720 USA.
[Meehan, Terrence F.] European Bioinformat Inst, European Mol Biol Lab, Cambridge CB10 1SD, England.
[Schmeier, Sebastian; Schaefer, Ulf; Medvedeva, Yulia A.; Alam, Intikhab; Archer, John A. C.; Jankovic, Boris R.; Marchand, Benoit; Pain, Arnab; Rashid, Mamoon; Bajic, Vladimir B.] KAUST, Computat Biosci Res Ctr, Thuwal 239556900, Saudi Arabia.
[Schmeier, Sebastian] Massey Univ, North Shore Mail Ctr, Inst Nat & Math Sci, Auckland 0745, New Zealand.
[Dimont, Emmanuel; Altschuler, Gabriel M.; Sui, Shannan J. Ho; Hofmann, Oliver M.; Hide, Winston] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Vitezic, Morana; Huminiecki, Lukasz] Karolinska Inst, Dept Cell & Mol Biol, SE-17177 Stockholm, Sweden.
[Semple, Colin A.; Young, Robert S.; Rennie, Sarah; Meynert, Alison; Prendergast, James G. D.; Taylor, Martin S.] Univ Edinburgh, Western Gen Hosp, MRC Human Genet Unit, MRC IGMM, Edinburgh EH4 2XU, Midlothian, Scotland.
[Francescatto, Margherita; Rizzu, Patrizia; Heutink, Peter] Vrije Univ Amsterdam, Dept Clin Genet, Med Ctr Amsterdam, NL-1081 BT Amsterdam, Netherlands.
[Francescatto, Margherita] Univ Porto, Grad Program Areas Basic & Appl Biol, Abel Salazar Biomed Sci Inst, P-4050313 Oporto, Portugal.
[Albanese, Davide; Chierici, Marco; Furlanello, Cesare; Jurman, Giuseppe; Roncador, Marco] Fdn Bruno Kessler, I-38123 Trento, Italy.
[Arner, Peter; Mejhert, Niklas] Karolinska Inst, Dept Med, Karolinska Univ Hosp, SE-14186 Huddinge, Sweden.
[Babina, Magda; Guhl, Sven] Univ Med Berlin, Dept Dermatol & Allergy, D-10117 Berlin, Germany.
[Balwierz, Piotr J.; Van Nimwegen, Erik] Univ Basel, Biozentrum, CH-4056 Basel, Switzerland.
[Beckhouse, Anthony G.; Briggs, James; Hitchens, Kelly J.; Ovchinnikov, Dmitry A.; Vijayan, Dipti; Wells, Christine A.; Wolvetang, Ernst] Univ Queensland, AIBN, St Lucia, Qld 4072, Australia.
[Beckhouse, Anthony G.; Blumenthal, Antje; Hitchens, Kelly J.; Vijayan, Dipti; Wells, Christine A.] Univ Queensland, Australian Infect Dis Res Ctr AID, St Lucia, Qld 4072, Australia.
[Pradhan-Bhatt, Swati] Univ Delaware, Dept Biol Sci, Newark, DE 19713 USA.
[Blake, Judith A.] Jackson Lab, Bar Harbor, ME 04609 USA.
[Blumenthal, Antje; Kenna, Tony J.] Univ Queensland, Diamantina Inst, St Lucia, Qld 4072, Australia.
[Bodega, Beatrice; Orlando, Valerio] IRCCS Fdn Santa Lucia, I-00143 Rome, Italy.
[Brombacher, Frank; Guler, Reto; Savvi, Suzana; Schwegmann, Anita] Int Ctr Genet Engn & Biotechnol ICGEB Cape Town C, ZA-7925 Cape Town, South Africa.
[Brombacher, Frank; Guler, Reto; Savvi, Suzana; Schwegmann, Anita] Univ Cape Town, Div Immunol, Inst Infect Dis & Mol Med IDM, ZA-7925 Cape Town, South Africa.
[Califano, Andrea] Columbia Univ, Med Ctr, Dept Syst Biol, New York, NY 10032 USA.
[Califano, Andrea] Columbia Univ, Med Ctr, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
[Califano, Andrea] Columbia Univ, Med Ctr, Dept Biomed Informat, New York, NY 10032 USA.
[Califano, Andrea; Shimoni, Yishai] Columbia Univ, Med Ctr, Herbert Irving Comprehens Canc Ctr, Inst Canc Genet, New York, NY 10032 USA.
[Cannistraci, Carlo V.; Orlando, Valerio; Pain, Arnab; Rashid, Mamoon; Ravasi, Timothy] KAUST, Biol & Environm Sci & Engn Div, Thuwal 239556900, Saudi Arabia.
[Cannistraci, Carlo V.; Ravasi, Timothy] KAUST, Appl Math & Computat Sci Program, Thuwal 239556900, Saudi Arabia.
[Carbajo, Daniel; Mar, Jessica C.] Albert Einstein Coll Med, Dept Syst & Computat Biol, Bronx, NY 10461 USA.
[Ciani, Yari; Dalla, Emiliano; Piazza, Silvano; Schneider, Claudio; Verardo, Roberto] LNCIB, I-34149 Trieste, Italy.
[Clevers, Hans C.; van de Wetering, Marc] Hubrecht Inst, NL-3584 CT Utrecht, Netherlands.
[Clevers, Hans C.] Royal Netherlands Acad Arts & Sci, NL-1000 GC Amsterdam, Netherlands.
[Clevers, Hans C.] Univ Med Ctr Utrecht, NL-3508 GA Utrecht, Netherlands.
[Davis, Carrie A.; Gingeras, Thomas] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11797 USA.
[Detmar, Michael; Krampitz, Sarah] ETH, Inst Pharmaceut Sci, CH-8093 Zurich, Switzerland.
[Diehl, Alexander D.] SUNY Buffalo, Dept Neurol, Sch Med & Biomed Sci, New York State Ctr Excellence Bioinformat & Life, Buffalo, NY 14203 USA.
[Dohi, Taeko; Kawamura, Yuki I.] Natl Ctr Global Hlth & Med, Res Ctr Hepatitis & Immunol Res Inst, Ichikawa, Chiba 2728516, Japan.
[Drablos, Finn; Rye, Morten B.] Norwegian Univ Sci & Technol NTNU, Dept Canc Res & Mol Med, NO-7491 Trondheim, Norway.
[Edge, Albert S. B.; Kempfle, Judith S.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA.
[Ekwall, Karl; Kere, Juha; Lennartsson, Andreas; Persson, Helena] Karolinska Inst, Dept Biosci & Nutr, Ctr Biosci, SE-14183 Huddinge, Sweden.
[Endoh, Mitsuhiro; Furusawa, Jun-ichi; Ikawa, Tomokatsu; Kawamoto, Hiroshi; Koseki, Haruhiko; Koyasu, Shigeo; Moro, Kazuyo; Ohno, Hiroshi; Okada-Hatakeyama, Mariko] RIKEN, RCAI, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
[Endoh, Mitsuhiro; Furusawa, Jun-ichi; Ikawa, Tomokatsu; Koseki, Haruhiko; Koyasu, Shigeo; Moro, Kazuyo; Ohno, Hiroshi; Okada-Hatakeyama, Mariko] RIKEN, Ctr Integrat Med Sci, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
[Enomoto, Hideki; Morimoto, Mitsuru; Sheng, Guojun; Yonekura, Yohei] RIKEN, CDB, Chuo Ku, Kobe, Hyogo 6500047, Japan.
[Fagiolini, Michela] Harvard Univ, Sch Med, FM Kirby Neurobiol Ctr, Childrens Hosp Boston, Boston, MA 02115 USA.
[Fang, Hai; Gough, Julian; Rackham, Owen J. L.] Univ Bristol, Dept Comp Sci, Bristol BS8 1UB, Avon, England.
[Farach-Carson, Mary C.] Rice Univ, Dept Biochem & Cell Biol, Houston, TX 77251 USA.
[Faulkner, Geoffrey J.] Mater Med Res Inst, Cancer Biol Program, South Brisbane, Qld 4101, Australia.
[Favorov, Alexander V.] Johns Hopkins Univ, Sch Med, Dept Oncol, Div Oncol Biostat & Bioinformat, Baltimore, MD 21205 USA.
[Favorov, Alexander V.] State Res Inst Genet & Select Ind Microorganisms, Moscow 117545, Russia.
[Frith, Martin C.] Natl Inst Adv Ind Sci & Technol, Computat Biol Res Ctr, Koto Ku, Tokyo 1350064, Japan.
[Fujita, Rie; Satoh, Hironori; Takai, Jun; Yamamoto, Masayuki] Tohoku Univ, Dept Med Biochem, Grad Sch Med, Aoba Ku, Sendai, Miyagi 9808575, Japan.
[Furusawa, Jun-ichi; Koyasu, Shigeo; Moro, Kazuyo] Keio Univ, Sch Med, Dept Microbiol & Immunol, Shinjuku Ku, Tokyo 1608582, Japan.
[Geijtenbeek, Teunis B.; van den Berg, Linda M.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands.
[Gibson, Andrew P.; Laros, Jeroen F. J.; Schultes, Erik A.; 't Hoen, Peter A. C.; Tatum, Zuotian; Thompson, Mark] Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 ZC Leiden, Netherlands.
[Goldowitz, Daniel; Ha, Thomas J.; Mathelier, Anthony; Wasserman, Wyeth W.; Zhang, Peter G.] Univ British Columbia, Dept Med Genet, Ctr Mol Med & Therapeut, Child & Family Res Inst, Vancouver, BC V5Z 4H4, Canada.
[Gustincich, Stefano; Zucchelli, Silvia] SISSA, I-34136 Trieste, Italy.
[Hamaguchi, Masahide; Morikawa, Hiromasa; Ohkura, Naganari; Sakaguchi, Shimon] Osaka Univ, Immunol Frontier Res Ctr, Suita, Osaka 5650871, Japan.
[Hara, Mitsuko; Kojima, Soichi] RIKEN, ASI, Wako, Saitama 3510198, Japan.
[Herlyn, Meenhard; Swoboda, Rolf K.; Zabierowski, Susan E.] Wistar Inst Anat & Biol, Melanoma Res Ctr, Philadelphia, PA 19104 USA.
[Iida, Kei; Kawaguchi, Shuji; Toyoda, Tetsuro] RIKEN, Bioinformat & Syst Engn Div BASE, Yokohama, Kanagawa 2300045, Japan.
[Jia, Hui; Lipovich, Leonard; Wood, Emily J.] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
[Kai, Chieko; Nakamura, Toshiyuki; Sato, Hiroki; Sugiyama, Takaaki; Yoneda, Misako] Univ Tokyo, Lab Anim Res Ctr, Inst Med Sci, Minato Ku, Tokyo 1088639, Japan.
[Kere, Juha] Sci Life Lab, SE-17121 Solna, Sweden.
[Khachigian, Levon M.; Patrikakis, Margaret] Univ New S Wales, Ctr Vasc Res, Sydney, NSW 2052, Australia.
[Kitamura, Toshio; Nakahara, Fumio] Univ Tokyo, Div Cellular Therapy, Inst Med Sci, Tokyo 1088639, Japan.
[Kitamura, Toshio; Nakahara, Fumio] Univ Tokyo, Div Stem Cell Signaling, Inst Med Sci, Tokyo 1088639, Japan.
[Klinken, S. Peter; Winteringham, Louise N.] Univ Western Australia, Harry Perkins Inst Med Res, QEII Med Ctr, Perth, WA 6009, Australia.
[Klinken, S. Peter; Winteringham, Louise N.] Univ Western Australia, Med Res Ctr, QEII Med Ctr, Perth, WA 6009, Australia.
[Knox, Alan J.] Univ Nottingham, City Hosp, Nottingham NG5 1PB, England.
[Lee, Weonju] Kyungpook Natl Univ, Sch Med, Dept Dermatol, Taegu 700721, South Korea.
[Mackay-sim, Alan] Griffith Univ, Natl Ctr Adult Stem Cell Res, Eskitis Inst Cell & Mol Therapies, Brisbane, Qld 4111, Australia.
[Mizuno, Yosuke; Nakachi, Yutaka; Okazaki, Yasushi] Saitama Med Univ, Div Funct Genom & Syst Med, Res Ctr Genom Med, Hidaka, Saitama 3501241, Japan.
[Morais, David A. de Lima] Univ Bristol, Fac Engn, Clifton BS81UB, England.
[Moro, Kazuyo] Japanese Sci & Technol Agcy JST, PRESTO, Tokyo 1020076, Japan.
[Motohashi, Hozumi] Tohoku Univ, Ctr Radioisotope Sci, Grad Sch Med, Aoba Ku, Sendai, Miyagi 9808575, Japan.
[Mummery, Christine L.; Passier, Robert] Leiden Univ, Med Ctr, NL-2300 RC Leiden, Netherlands.
[Nakachi, Yutaka; Okazaki, Yasushi] Saitama Med Univ, Div Translat Res, Res Ctr Genom Med, Hidaka, Saitama 3501241, Japan.
[Nakamura, Yukio] RIKEN, BioResource Ctr BRC, Tsukuba, Ibaraki 3050074, Japan.
[Nozaki, Tadasuke; Toyoda, Hiroo] Tokyo Univ Pharm & Life Sci, Dept Clin Mol Genet, Sch Pharm, Hachioji, Tokyo 1920392, Japan.
[Ogishima, Soichi; Tanaka, Hiroshi] Tokyo Med & Dent Univ, Dept Bioinformat, Med Res Inst, Bunkyo Ku, Tokyo 1138510, Japan.
[Ohshima, Mitsuhiro] Ohu Univ, Dept Biochem, Sch Pharmaceut Sci, Koriyama, Fukushima 9638611, Japan.
[Sajantila, Antti] Univ Helsinki, Dept Forens Med, Hjelt Inst, Helsinki 003000, Finland.
[Schneider, Claudio] Univ Udine, DSMB, I-33100 Udine, Italy.
[Schulze-Tanzil, Gundula G.] Charite, Dept Orthoped Trauma & Reconstruct Surg, D-14195 Berlin, Germany.
[Sugiyama, Daisuke] Kyushu Univ Hosp, Ctr Clin & Translat Reseach, Higashi Ku, Fukuoka 8128582, Japan.
[Tatsukawa, Hideki] Nagoya Univ, Grad Sch Pharmaceut Sci, Chikusa Ku, Nagoya, Aichi 4648601, Japan.
[Valen, Eivind] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
[Yamaguchi, Yoko] Nihon Univ, Dept Biochem, Sch Dent, Chiyoda Ku, Tokyo 1018310, Japan.
[Lenhard, Boris] Univ Bergen, Dept Informat, NO-5008 Bergen, Norway.
[Makeev, Vsevolod J.] MIPT, Dept Biol & Med Phys, Dolgoprudnyi 141700, Moscow Region, Russia.
RP Forrest, ARR (reprint author), RIKEN, OSC, Tsurumi Ku, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan.
EM alistair.forrest@gmail.com; carninci@riken.jp; yosihide@gsc.riken.jp
RI Daub, Carsten/A-7436-2010; Lassmann, Timo/A-8271-2008; Carninci,
Piero/K-1568-2014; Sandelin, Albin/G-2881-2011; Kere, Juha/A-9179-2008;
Sakaguchi, Shimon/C-9535-2009; Hide, Winston Hide/C-7217-2009; Kenna,
Tony/A-6035-2011; Cannistraci, Carlo Vittorio/G-1710-2014; Zhao,
Xiaobei/G-3567-2014; Sheng, Guojun/G-4116-2014; Andersson,
Robin/B-5311-2009; Koseki, Haruhiko/I-3825-2014; de Hoon,
Michiel/N-8006-2015; Suzuki, Harukazu/N-9553-2015; Kojima,
Soichi/N-7104-2015; Nakamura, Yukio/A-5263-2016; KONDO,
NAOTO/A-5829-2016; Moro, Kazuyo/A-5987-2016; Kawai, Jun/A-6451-2016;
Koyasu, Shigeo/J-5583-2015; Semple, Colin/A-5613-2009; U-ID,
Kyushu/C-5291-2016; Vorontsov, Ilya/C-6333-2014; Diehl,
Alexander/G-9883-2016; Mackay-Sim, Alan/C-3431-2008; Ovchinnikov,
Dmitry/J-7963-2014; Vitezic, Morana/A-6165-2013; Ravasi,
Timothy/B-8777-2008; Rehli, Michael/E-9093-2011; Ohno,
Hiroshi/L-7899-2014; Wasserman, Wyeth/I-4866-2015; Sheng,
Guojun/I-4900-2015; Pain, Arnab/L-5766-2015; Beckhouse,
Anthony/A-2601-2010; Summers, Kim/M-4086-2015; Arner, Erik/A-1895-2010;
Kasukawa, Takeya/N-5070-2015; Plessy, Charles/N-5054-2015; Itoh,
Masayoshi/N-5363-2015; Schmeier, Sebastian/D-4731-2011; Kawaji,
Hideya/N-5116-2015; Wolvetang, Ernst/D-6644-2017; Kwon,
Andrew/D-4625-2017; Kaczkowski, Bogumil/D-5336-2017; Bertin,
Nicolas/C-3025-2008; Archer, John/D-5200-2012; Bajic,
Vladimir/D-2810-2009; Katayama, Shintaro/F-2958-2010;
OI Daub, Carsten/0000-0002-3295-8729; Lassmann, Timo/0000-0002-0138-2691;
Carninci, Piero/0000-0001-7202-7243; Sandelin,
Albin/0000-0002-7109-7378; Kere, Juha/0000-0003-1974-0271; Hide, Winston
Hide/0000-0002-8621-3271; Cannistraci, Carlo
Vittorio/0000-0003-0100-8410; Zhao, Xiaobei/0000-0002-5277-0846;
Andersson, Robin/0000-0003-1516-879X; Koseki,
Haruhiko/0000-0001-8424-5854; Suzuki, Harukazu/0000-0002-8087-0836;
Kojima, Soichi/0000-0002-5252-1612; KONDO, NAOTO/0000-0001-9576-7615;
Koyasu, Shigeo/0000-0001-9585-3038; Semple, Colin/0000-0003-1765-4118;
Vorontsov, Ilya/0000-0001-8888-0804; Diehl,
Alexander/0000-0001-9990-8331; Mackay-Sim, Alan/0000-0003-4446-5371;
Ovchinnikov, Dmitry/0000-0001-9603-8385; Vitezic,
Morana/0000-0002-7994-9600; Rehli, Michael/0000-0003-3992-932X; Ohno,
Hiroshi/0000-0001-8776-9661; Pain, Arnab/0000-0002-1755-2819; Beckhouse,
Anthony/0000-0002-5141-8250; Summers, Kim/0000-0002-7084-4386; Arner,
Erik/0000-0003-1225-4908; Kasukawa, Takeya/0000-0001-5085-0802; Plessy,
Charles/0000-0001-7410-6295; Itoh, Masayoshi/0000-0002-1772-318X;
Schmeier, Sebastian/0000-0002-3947-8226; Kawaji,
Hideya/0000-0002-0575-0308; Kwon, Andrew/0000-0001-5019-8156;
Kaczkowski, Bogumil/0000-0001-6554-5608; Bertin,
Nicolas/0000-0002-9835-9606; Bajic, Vladimir/0000-0001-5435-4750;
Katayama, Shintaro/0000-0001-7581-5157; Harbers,
Matthias/0000-0002-5613-7220; Kenna, Tony/0000-0001-6844-3463; Gingeras,
Thomas/0000-0001-9106-3573; Alam, Intikhab/0000-0001-5306-847X; Taylor,
Martin/0000-0001-7656-330X; Chierici, Marco/0000-0001-9791-9301;
Persson, Helena/0000-0002-5187-6446; van Nimwegen,
Erik/0000-0001-6338-1312; Fang, Hai/0000-0003-3961-8572; Morikawa,
Hiromasa/0000-0002-6793-5885; Hamaguchi, Masahide/0000-0002-8651-4445;
Ravasi, Timothy/0000-0002-9950-465X; Lenhard, Boris/0000-0002-1114-1509;
Lennartsson, Andreas/0000-0002-3272-2505; Rackham,
Owen/0000-0002-4390-0872; Furlanello, Cesare/0000-0002-5384-3605;
Hofmann, Oliver/0000-0002-7738-1513; Fisher,
Malcolm/0000-0003-1074-8103; Frith, Martin/0000-0003-0998-2859; Rashid,
Mamoon/0000-0003-4851-4994; Jurman, Giuseppe/0000-0002-2705-5728; Valen,
Eivind/0000-0003-1840-6108; Meehan, Terrence/0000-0003-1980-3228;
Prendergast, James/0000-0001-8916-018X; Wells,
Christine/0000-0003-3133-3628; Forrest, Alistair/0000-0003-4543-1675;
Ciani, Yari/0000-0002-9635-2830
FU MEXT; MEXT, Japan; Research Grants for RIKEN Preventive Medicine and
Diagnosis Innovation Program(RIKEN PMI); RIKEN Centre for Life Science
Technologies, Division of Genomic Technologies (RIKEN CLST (DGT)) from
the MEXT, Japan
FX FANTOM5 was made possible by a Research Grant for RIKEN Omics Science
Center from MEXT to Y. Hayashizaki and a grant of the Innovative Cell
Biology by Innovative Technology (Cell Innovation Program) from the
MEXT, Japan to Y. Hayashizaki. It was also supported by Research Grants
for RIKEN Preventive Medicine and Diagnosis Innovation Program(RIKEN
PMI) to Y. Hayashizaki and RIKEN Centre for Life Science Technologies,
Division of Genomic Technologies (RIKEN CLST (DGT)) from the MEXT,
Japan. Extended acknowledgements are provided in the Supplementary
Information.
NR 54
TC 313
Z9 315
U1 16
U2 140
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 27
PY 2014
VL 507
IS 7493
BP 462
EP +
DI 10.1038/nature13182
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6WN
UT WOS:000333402000033
ER
PT J
AU Liu, HP
Moynihan, KD
Zheng, YR
Szeto, GL
Li, AV
Huang, B
Van Egeren, DS
Park, C
Irvine, DJ
AF Liu, Haipeng
Moynihan, Kelly D.
Zheng, Yiran
Szeto, Gregory L.
Li, Adrienne V.
Huang, Bonnie
Van Egeren, Debra S.
Park, Clara
Irvine, Darrell J.
TI Structure-based programming of lymph-node targeting in molecular
vaccines
SO NATURE
LA English
DT Article
ID IMMUNE-RESPONSE; DELIVERY; CELLS; OLIGONUCLEOTIDES; VACCINATION; ANTIGEN
AB In cancer patients, visual identification of sentinel lymph nodes (LNs) is achieved by the injection of dyes that bind avidly to endogenous albumin, targeting these compounds to LNs, where they are efficiently filtered by resident phagocytes(1,2). Here we translate this 'albumin hitchhiking' approach to molecular vaccines, through the synthesis of amphiphiles (amph-vaccines) comprising an antigen or adjuvant cargo linked to a lipophilic albumin-binding tail by a solubility-promoting polar polymer chain. Administration of structurally optimized CpG-DNA/peptide amph-vaccines in mice resulted in marked increases in LN accumulation and decreased systemic dissemination relative to their parent compounds, leading to 30-fold increases in T-cell priming and enhanced anti-tumour efficacy while greatly reducing systemic toxicity. Amph-vaccines provide a simple, broadly applicable strategy to simultaneously increase the potency and safety of subunit vaccines.
C1 [Liu, Haipeng; Irvine, Darrell J.] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA.
[Liu, Haipeng; Moynihan, Kelly D.; Zheng, Yiran; Szeto, Gregory L.; Li, Adrienne V.; Huang, Bonnie; Park, Clara; Irvine, Darrell J.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA.
[Liu, Haipeng; Moynihan, Kelly D.; Zheng, Yiran; Szeto, Gregory L.; Li, Adrienne V.; Huang, Bonnie; Irvine, Darrell J.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
[Van Egeren, Debra S.] MIT, Dept Biol, Cambridge, MA 02139 USA.
[Irvine, Darrell J.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA 02139 USA.
[Irvine, Darrell J.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
RP Irvine, DJ (reprint author), MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA.
EM djirvine@mit.edu
OI Van Egeren, Debra/0000-0002-4017-0413; Szeto,
Gregory/0000-0001-7604-1333
FU Koch Institute from the National Cancer Institute [P30-CA14051];
National Institutes of Health [AI091693, AI104715, AI095109]; Department
of Defense [W911NF-13-D-0001, W911NF-07-D-0004, T.O. 8]; Ragon Institute
of Massachusetts General Hospital; Massachusetts Institute of Technology
and Harvard
FX This work was supported in part by the Koch Institute Support (core)
grant P30-CA14051 from the National Cancer Institute, the National
Institutes of Health (grants AI091693, AI104715 and AI095109), the
Department of Defense (W911NF-13-D-0001 and W911NF-07-D-0004, T.O. 8)
and the Ragon Institute of Massachusetts General Hospital, the
Massachusetts Institute of Technology and Harvard. D.J.I. is an
investigator of the Howard Hughes Medical Institute. We thank T. C. Wu
for kindly providing the TC-1 tumour cells. We thank the Koch Institute
Swanson Biotechnology Center for technical support, specifically the
applied therapeutics and whole animal imaging core facility, histology
and flow cytometry core facility. The authors acknowledge the service to
the MIT community of the late Sean Collier.
NR 28
TC 113
Z9 114
U1 8
U2 125
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 27
PY 2014
VL 507
IS 7493
BP 519
EP +
DI 10.1038/nature12978
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6WN
UT WOS:000333402000045
PM 24531764
ER
PT J
AU Liu, S
An, J
Lin, JH
Liu, YL
Bao, LD
Zhang, W
Zhao, JJ
AF Liu, Shuang
An, Jie
Lin, Jianhong
Liu, Yanli
Bao, Lidao
Zhang, Wen
Zhao, Jian-Jun
TI Single Nucleotide Polymorphisms of MicroRNA Processing Machinery Genes
and Outcome of Hepatocellular Carcinoma
SO PLOS ONE
LA English
DT Article
ID NUCLEAR EXPORT; CANCER; EPIDEMIOLOGY; PRECURSORS; CHINA; RISK
AB MicroRNA (miRNA)-related single nucleotide polymorphisms (miR-SNPs) can affect cancer development, treatment efficacy and patients prognosis. We examined 6 miR-SNPs in miRNA processing machinery genes including exportin 5 (XPO5) (rs11077), Ran-GTPase (RAN) (rs14035), Dicer (rs3742330), Trinucleotide Repeat Containing 6B (TNRC6B) (rs9623117), GEMIN3 (rs197412), GEMIN4 (rs2740348) in 108 surgically resected HCC patients and evaluated the impact of these miR-SNPs on HCC outcome. Among the 6 SNPs, only the A/A genotype of rs11077 located in XPO5 3'UTR was identified to associated independently with worse survival in HCC patients by multivariate analysis with relative risk, 0.395; 95% CI, 0.167-0.933; p = 0.034. This is the first study reporting that polymorphisms related to miRSNPs have prognostic value in hepatocellular carcinoma and identify the A/A genotype of rs11077 SNP site located in XPO5 3'UTR can help to predict worse prognosis in patients.
C1 [Liu, Shuang; An, Jie; Liu, Yanli; Zhang, Wen] Bethune Int Peace Hosp, Dept Pathol, Shijiazhuang, Peoples R China.
[Lin, Jianhong; Bao, Lidao; Zhao, Jian-Jun] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Liu, S (reprint author), Bethune Int Peace Hosp, Dept Pathol, Shijiazhuang, Peoples R China.
EM Liu_Shuang11@hotmail.com; Jianjun_zhao@dfci.harvard.edu
FU Bethune International Peace Hospital (BIPH) research grant; SPORE career
development award from Dana-Farber Cancer Institute (DFCI); Multiple
Myeloma Research Foundation (MMRF) award
FX SL is supported by Bethune International Peace Hospital (BIPH) research
grant. JL is supported by SPORE career development award from
Dana-Farber Cancer Institute (DFCI). JJZ is supported by Multiple
Myeloma Research Foundation (MMRF) award. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 23
TC 15
Z9 17
U1 0
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 27
PY 2014
VL 9
IS 3
AR e92791
DI 10.1371/journal.pone.0092791
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE0SW
UT WOS:000333677500039
PM 24676133
ER
PT J
AU Sharma, RK
Makino, CL
Hicks, D
Duda, T
AF Sharma, Rameshwar K.
Makino, Clint L.
Hicks, David
Duda, Teresa
TI ROS-GC interlocked Ca2+-sensor S100B protein signaling in cone
photoreceptors: review
SO FRONTIERS IN MOLECULAR NEUROSCIENCE
LA English
DT Review
DE ROS-GC guanylate cyclase; cyclic GMP; phototransduction; cones; S100B
ID MEMBRANE GUANYLATE-CYCLASE; NATRIURETIC-FACTOR RECEPTOR; OUTER SEGMENT;
ACTIVATING PROTEIN; FUNCTIONAL-CHARACTERIZATION; CA2+ SENSOR; MOLECULAR
CHARACTERIZATION; PEPTIDE RECEPTOR; RHODOPSIN KINASE; WILD-TYPE
AB Photoreceptor rod outer segment membrane guanylate cyclase (ROS-GC) is central to visual transduction; it generates cyclic GMP the second messenger of the photon signal. Photoexcited rhodopsin initiates a biochemical cascade that leads to a drop in the intracellular level of cyclic GMP and closure of cyclic nucleotide gated ion channels. Recovery of the photoresponse requires resynthesis of cyclic GMP typically by a pair of ROS-GCs, 1 and 2. In rods, ROS-GCs exist as complexes with guanylate cyclase activating proteins (GCAPs), which are Ca2+-sensing elements. There is a light-induced fall in intracellular Ca2+. As Ca2+ dissociates from GCAPs in the 20-200 nM range, ROS-GC activity rises to quicken the photoresponse recovery. GCAPs then progressively turn down ROS-GC activity as Ca2+ and cyclic G MP levels return to baseline. To date, GCAPs mediate the only known mechanism of ROS-GC regulation in the photoreceptors. However, in mammalian cone outer segments, cone synapses and ON bipolar cells, another Ca2+ sensor protein, S100B, complexes with ROS-GC1 and senses the Ca2+ signal with a K-1/2 of 400 nM. Unlike GCAPs, S100B stimulates ROS-GC activity when Ca2+ is bound. Thus, the ROS-GC system in cones functions as a Ca2+ bimodal switch; with rising intracellular Ca2+, its activity is first turned down by GCAPs and then turned up by S100B. This presentation provides a historical perspective on the role of S100B in the photoreceptors, offers a pictorial model for the "bimodal" operation of the ROS-GC switch and projects future tasks that are needed to understand its operation. Some accounts of this review have been adopted from the original publications of these authors.
C1 [Sharma, Rameshwar K.; Duda, Teresa] Salus Univ, Res Div Biochem & Mol Biol, Unit Regulatory & Mol Biol, Elkins Pk, PA 19207 USA.
[Makino, Clint L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA.
[Hicks, David] CNRS, Inst Cellular & Integrat Neurosci, Dept Neurobiol Rhythms, CNRSUPR3212, Strasbourg, France.
RP Sharma, RK (reprint author), Salus Univ, Res Div Biochem & Mol Biol, Unit Regulatory & Mol Biol, 8360 Old York Rd, Elkins Pk, PA 19207 USA.
EM rsharma@salus.edu; Clint_Makino@meei.harvard.edu; tduda@salus.edu
OI Makino, Clint/0000-0002-6005-9069
FU National Institutes of Health; National Science Foundation; Damon Runyon
Walter Winchell Cancer Fund; Howe Laboratory Endowment of the
Massachusetts Eye and Ear Infirmary
FX The authors gratefuily acknowledge the continuous past support by the
numerous USPHS award from the National Institutes of Health, the
beginning award from the National Science Foundation and the Damon
Runyon Walter Winchell Cancer Fund and the Howe Laboratory Endowment of
the Massachusetts Eye and Ear Infirmary.
NR 66
TC 7
Z9 7
U1 0
U2 3
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5099
J9 FRONT MOL NEUROSCI
JI Front. Molec. Neurosci.
PD MAR 26
PY 2014
VL 7
AR 21
DI 10.3389/fnmol.2014.00021
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA AZ0WT
UT WOS:000347963500001
PM 24723847
ER
PT J
AU Bang, A
Bellad, R
Gisore, P
Hibberd, P
Patel, A
Goudar, S
Esamai, F
Goco, N
Meleth, S
Derman, RJ
Liechty, EA
McClure, E
Carlo, WA
Wright, LL
AF Bang, Akash
Bellad, Roopa
Gisore, Peter
Hibberd, Patricia
Patel, Archana
Goudar, Shivaprasad
Esamai, Fabian
Goco, Norman
Meleth, Sreelatha
Derman, Richard J.
Liechty, Edward A.
McClure, Elizabeth
Carlo, Waldemar A.
Wright, Linda L.
TI Implementation and evaluation of the Helping Babies Breathe curriculum
in three resource limited settings: does Helping Babies Breathe save
lives? A study protocol
SO BMC PREGNANCY AND CHILDBIRTH
LA English
DT Article
DE Neonatal mortality; Perinatal mortality; Asphyxia; Stillbirth; Helping
Babies Breathe; Resuscitation; Bag and mask ventilation; >= 1500 grams
ID NEONATAL RESUSCITATION; PERINATAL-MORTALITY; DEVELOPING-COUNTRY
AB Background: Neonatal deaths account for over 40% of all under-5 year deaths; their reduction is increasingly critical for achieving Millennium Development Goal 4. An estimated 3 million newborns die annually during their first month of life; half of these deaths occur during delivery or within 24 hours. Every year, 6 million babies require help to breathe immediately after birth. Resuscitation training to help babies breathe and prevent/manage birth asphyxia is not routine in low-middle income facility settings. Helping Babies Breathe (HBB), a simulation-training program for babies wherever they are born, was developed for use in low-middle income countries. We evaluated whether HBB training of facility birth attendants reduces perinatal mortality in the Eunice Kennedy Shriver National Institute of Child Health and Human Development's Global Network research sites.
Methods/design: We hypothesize that a two-year prospective pre-post study to evaluate the impact of a facility-based training package, including HBB and essential newborn care, will reduce all perinatal mortality (fresh stillbirth or neonatal death prior to 7 days) among the Global Network's Maternal Neonatal Health Registry births >= 1500 grams in the study clusters served by the facilities. We will also evaluate the effectiveness of the HBB training program changing on facility-based perinatal mortality and resuscitation practices. Seventy-one health facilities serving 52 geographically-defined study clusters in Belgaum and Nagpur, India, and Eldoret, Kenya, and 30,000 women will be included. Primary outcome data will be collected by staff not involved in the HBB intervention. Additional data on resuscitations, resuscitation debriefings, death audits, quality monitoring and improvement will be collected. HBB training will include training of MTs, facility level birth attendants, and quality monitoring and improvement activities.
Discussion: Our study will evaluate the effect of a HBB/ENC training and quality monitoring and improvement package on perinatal mortality using a large multicenter design and approach in 71 resource-limited health facilities, leveraging an existing birth registry to provide neonatal outcomes through day 7. The study will provide the evidence base, lessons learned, and best practices that will be essential to guiding future policy and investment in neonatal resuscitation.
C1 [Bang, Akash] Mahatma Gandhi Inst Med Sci, Sevagram, India.
[Bellad, Roopa; Goudar, Shivaprasad] KLEs Jawaharlal Nehru Med Coll, Belgaum, India.
[Gisore, Peter; Esamai, Fabian] Moi Univ, Eldoret, Kenya.
[Hibberd, Patricia] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Patel, Archana] Lata Med Res Fdn, Nagpur, Maharashtra, India.
[Goco, Norman; Meleth, Sreelatha; McClure, Elizabeth] RTI Int, Durham, NC USA.
[Derman, Richard J.] Christiana Care, Newark, DE USA.
[Liechty, Edward A.] Indiana Univ, Indianapolis, IN 46204 USA.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Birmingham, AL USA.
[Wright, Linda L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Bang, A (reprint author), Mahatma Gandhi Inst Med Sci, Sevagram, India.
EM drakashbang@gmail.com
OI GOUDAR, SHIVAPRASAD/0000-0002-8680-7053
FU Laerdal Foundation; Norad; NICHD [U01 HD040636, U01 HD058322, U01
HD042372, U01 HD058326]
FX We thank the Scientific Advisory Board members, Alan H Jobe, MD, PhD;
William J Keenan, MD and Petter Andreas Steen, MD for their oversight
and guidance. This study was funded with grants from the Laerdal
Foundation, Norad, and the NICHD (grant numbers U01 HD040636; U01
HD058322; U01 HD042372; U01 HD058326).
NR 18
TC 18
Z9 18
U1 2
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2393
J9 BMC PREGNANCY CHILDB
JI BMC Pregnancy Childbirth
PD MAR 26
PY 2014
VL 14
AR 116
DI 10.1186/1471-2393-14-116
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA AF8CK
UT WOS:000334942700001
PM 24670013
ER
PT J
AU Pitroda, SP
Pashtan, IM
Logan, HL
Budke, B
Darga, TE
Weichselbaum, RR
Connell, PP
AF Pitroda, Sean P.
Pashtan, Itai M.
Logan, Hillary L.
Budke, Brian
Darga, Thomas E.
Weichselbaum, Ralph R.
Connell, Philip P.
TI DNA Repair Pathway Gene Expression Score Correlates with Repair
Proficiency and Tumor Sensitivity to Chemotherapy
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID STRAND BREAK REPAIR; CELL LUNG-CANCER; HOMOLOGOUS RECOMBINATION;
MAMMALIAN-CELLS; ADJUVANT CHEMOTHERAPY; END RESECTION; RAD51;
OVEREXPRESSION; INSTABILITY; PROTEIN
AB Mutagenesis is a hallmark of malignancy, and many oncologic treatments function by generating additional DNA damage. Therefore, DNA damage repair is centrally important in both carcinogenesis and cancer treatment. Homologous recombination (HR) and nonhomologous end joining are alternative pathways of double-strand DNA break repair. We developed a method to quantify the efficiency of DNA repair pathways in the context of cancer therapy. The recombination proficiency score (RPS) is based on the expression levels for four genes involved in DNA repair pathway preference (Rif1, PARI, RAD51, and Ku80), such that high expression of these genes yields a low RPS. Carcinoma cells with low RPS exhibit HR suppression and frequent DNA copy number alterations, which are characteristic of error-prone repair processes that arise in HR-deficient backgrounds. The RPS system was clinically validated in patients with breast or non-small cell lung carcinomas (NSCLCs). Tumors with low RPS were associated with greater mutagenesis, adverse clinical features, and inferior patient survival rates, suggesting that HR suppression contributes to the genomic instability that fuels malignant progression. This adverse prognosis associated with low RPS was diminished if NSCLC patients received adjuvant chemotherapy, suggesting that HR suppression and associated sensitivity to platinum-based drugs counteract the adverse prognosis associated with low RPS. Therefore, RPS may help oncologists select which therapies will be effective for individual patients, thereby enabling more personalized care.
C1 [Pitroda, Sean P.; Logan, Hillary L.; Budke, Brian; Darga, Thomas E.; Weichselbaum, Ralph R.; Connell, Philip P.] Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60647 USA.
[Pashtan, Itai M.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA.
[Pashtan, Itai M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02215 USA.
[Weichselbaum, Ralph R.] Univ Chicago, Ludwig Ctr Metastasis Res, Chicago, IL 60647 USA.
RP Connell, PP (reprint author), Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60647 USA.
EM pconnell@radonc.uchicago.edu
OI Darga, Thomas/0000-0002-8968-6701
FU NIH [CA142642-02]; Ludwig Foundation for Cancer Research; Lung Cancer
Research Foundation
FX Funding: This work was supported by funding from the NIH (CA142642-02
2010-2015 to P. P. C.), Ludwig Foundation for Cancer Research (to R. R.
W.), and the Lung Cancer Research Foundation (to R.R.W.).
NR 61
TC 13
Z9 13
U1 0
U2 5
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD MAR 26
PY 2014
VL 6
IS 229
AR 229ra42
DI 10.1126/scitranslmed.3008291
PG 10
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA AE3UR
UT WOS:000333904300007
PM 24670686
ER
PT J
AU Hiraki, LT
Joshi, AD
Ng, K
Fuchs, CS
Ma, J
Hazra, A
Peters, U
Karlson, EW
Giovannucci, E
Kraft, P
Chan, AT
AF Hiraki, Linda T.
Joshi, Amit D.
Ng, Kimmie
Fuchs, Charles S.
Ma, Jing
Hazra, Aditi
Peters, Ulrike
Karlson, Elizabeth W.
Giovannucci, Edward
Kraft, Peter
Chan, Andrew T.
TI Joint Effects of Colorectal Cancer Susceptibility Loci, Circulating
25-Hydroxyvitamin D Risk of Colorectal Cancer
SO PLOS ONE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; VITAMIN-D; COLON-CANCER; PHYSICIANS HEALTH;
METAANALYSIS; WOMEN; CALCIUM; DISEASE; MEN; SCAN
AB Background: Genome wide association studies (GWAS) have identified several SNPs associated with colorectal cancer (CRC) susceptibility. Vitamin D is also inversely associated with CRC risk.
Methods: We examined main and joint effects of previously GWAS identified genetic markers of CRC and plasma 25-hydroxyvitamin D (25(OH)D) on CRC risk in three prospective cohorts: the Nurses' Health Study (NHS), the Health Professionals Follow-up Study (HPFS), and the Physicians' Health Study (PHS). We included 1895 CRC cases and 2806 controls with genomic DNA. We calculated odds ratios and 95% confidence intervals for CRC associated with additive genetic risk scores (GRSs) comprised of all CRC SNPs and subsets of these SNPs based on proximity to regions of increased vitamin D receptor binding to vitamin D response elements (VDREs), based on published ChiP-seq data. Among a subset of subjects with additional prediagnostic 25(OH)D we tested multiplicative interactions between plasma 25(OH)D and GRS's. We used fixed effects models to meta-analyze the three cohorts.
Results: The per allele multivariate OR was 1.12 (95% CI, 1.06-1.19) for GRS-proximalVDRE; and 1.10 (95% Cl, 1.06-1.14) for GRS-nonproxVDRE. The lowest quartile of plasma 25(OH)D compared with the highest, had a multivariate OR of 0.63 (95% Cl, 0.48-0.82) for CRC. We did not observe any significant interactions between any GRSs and plasma 25(OH)D.
Conclusions: We did not observe evidence for the modification of genetic susceptibility for CRC according to vitamin D status, or evidence that the effect of common CRC risk alleles differed according to their proximity to putative VDR binding sites.
C1 [Hiraki, Linda T.; Joshi, Amit D.; Hazra, Aditi; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Ng, Kimmie; Fuchs, Charles S.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Fuchs, Charles S.; Ma, Jing; Hazra, Aditi; Giovannucci, Edward; Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Fuchs, Charles S.; Ma, Jing; Hazra, Aditi; Karlson, Elizabeth W.; Giovannucci, Edward; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA.
[Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Karlson, Elizabeth W.] Brigham & Womens Hosp, Dept Med, Div Rheumatol, Boston, MA 02115 USA.
[Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Chan, Andrew T.] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA.
RP Chan, AT (reprint author), Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
EM ACHAN@partners.org
FU National Cancer Institute, National Institutes of Health, U.S.
Department of Health and Human Services [U01 CA137088, R01 CA059045, RO1
CA137178, K24 DK098311]; Canadian Institute of Health Research (CIHR)
Fellowship Award; NIH [5K07CA148894]
FX Support was provided by National Cancer Institute, National Institutes
of Health, U.S. Department of Health and Human Services (U01 CA137088;
R01 CA059045; RO1 CA137178; K24 DK098311). Dr. Hiraki was supported by a
Canadian Institute of Health Research (CIHR) Fellowship Award, Dr. Ng
was supported by an NIH 5K07CA148894 award. Dr. Chan is a Damon Runyon
Clinical Investigator. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 38
TC 3
Z9 3
U1 1
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 26
PY 2014
VL 9
IS 3
AR e92212
DI 10.1371/journal.pone.0092212
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE0SR
UT WOS:000333677000036
PM 24670869
ER
PT J
AU Muller, LPD
Sargoy, A
Rodriguez, AR
Brecha, NC
AF Mueller, Luis Perez de Sevilla
Sargoy, Allison
Rodriguez, Allen R.
Brecha, Nicholas C.
TI Melanopsin Ganglion Cells Are the Most Resistant Retinal Ganglion Cell
Type to Axonal Injury in the Rat Retina
SO PLOS ONE
LA English
DT Article
ID OPTIC-NERVE SECTION; MOUSE RETINA; ADULT-RATS; SURVIVAL; PROTEIN;
NEURONS; MICE; AKT; MORPHOLOGY; APOPTOSIS
AB We report that the most common retinal ganglion cell type that remains after optic nerve transection is the M1 melanopsin ganglion cell. M1 ganglion cells are members of the intrinsically photosensitive retinal ganglion cell population that mediates non-image-forming vision, comprising similar to 2.5% of all ganglion cells in the rat retina. In the present study, M1 ganglion cells comprised 1.7 +/- 1%, 28 +/- 14%, 55 +/- 13% and 82 +/- 8% of the surviving ganglion cells 7, 14, 21 and 60 days after optic nerve transection, respectively. Average M1 ganglion cell somal diameter and overall morphological appearance remained unchanged in non-injured and injured retinas, suggesting a lack of injury-induced degeneration. Average M1 dendritic field size increased at 7 and 60 days following optic nerve transection, while average dendritic field size remained similar in non-injured retinas and in retinas at 14 and 21 days after optic nerve transection. These findings demonstrate that M1 ganglion cells are more resistant to injury than other ganglion cell types following optic nerve injury, and provide an opportunity to develop pharmacological or genetic therapeutic approaches to mitigate ganglion cell death and save vision following optic nerve injury.
C1 [Mueller, Luis Perez de Sevilla; Sargoy, Allison; Rodriguez, Allen R.; Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA.
[Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Sargoy, Allison; Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA.
[Brecha, Nicholas C.] Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA.
[Brecha, Nicholas C.] Vet Adm Greater Los Angeles Hlth Syst, Los Angeles, CA USA.
RP Muller, LPD (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA.
EM luisperez@mednet.ucla.edu
FU Telemedicine & Advanced Technology Research Center (TATRC), at Fort
Detrick, MD [W81XWH-10-2-0077]; NIH [EY04067]; NIDDK [P30 DK41301]; VA
Merit Review; VA Career Research Scientist
FX This research and development project was conducted by the authors at
the David Geffen School of Medicine at UCLA and is made possible by a
contract agreement that was awarded and administered by the U.S. Army
Medical Research & Materiel Command (USAMRMC) and the Telemedicine &
Advanced Technology Research Center (TATRC), at Fort Detrick, MD under
Contract Number: W81XWH-10-2-0077. Support for these studies also came
from NIH EY04067, NIDDK P30 DK41301 (UCLA Cure Center Core) and a VA
Merit Review (NB). NCB is a VA Career Research Scientist. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 62
TC 17
Z9 17
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 26
PY 2014
VL 9
IS 3
AR e93274
DI 10.1371/journal.pone.0093274
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE0SR
UT WOS:000333677000130
ER
PT J
AU Nettiksimmons, J
Simonsick, EM
Harris, T
Satterfield, S
Rosano, C
Yaffe, K
AF Nettiksimmons, Jasmine
Simonsick, Eleanor M.
Harris, Tamara
Satterfield, Suzanne
Rosano, Caterina
Yaffe, Kristine
CA Hlth ABC Study
TI The Associations between Serum Brain-Derived Neurotrophic Factor,
Potential Confounders, and Cognitive Decline: A Longitudinal Study
SO PLOS ONE
LA English
DT Article
ID BDNF MESSENGER-RNA; ALZHEIMERS-DISEASE; CARDIORESPIRATORY FITNESS;
DECREASED-LEVELS; BLOOD-BRAIN; IMPAIRMENT; DEPRESSION; SURVIVAL;
NEURONS; MEN
AB Brain-derived neurotrophic factor (BDNF) plays a role in the maintenance and function of neurons. Although persons with Alzheimer's disease have lower cortical levels of BDNF, evidence regarding the association between circulating BDNF and cognitive function is conflicting. We sought to determine the correlates of BDNF level and whether BDNF level was prospectively associated with cognitive decline in healthy older adults. We measured serum BDNF near baseline in 912 individuals. Cognitive status was assessed repeatedly with the modified Mini-Mental Status Examination and the Digit Symbol Substitution test over the next 10 years. We evaluated the association between BDNF and cognitive decline with longitudinal models. We also assessed the association between BDNF level and demographics, comorbidities and health behaviors. We found an association between serum BDNF and several characteristics that are also associated with dementia (race and depression), suggesting that future studies should control for these potential confounders. We did not find evidence of a longitudinal association between serum BDNF and subsequent cognitive test trajectories in older adults, although we did identify a potential trend toward a cross-sectional association. Our results suggest that serum BDNF may have limited utility as a biomarker of prospective cognitive decline.
C1 [Nettiksimmons, Jasmine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
[Simonsick, Eleanor M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Harris, Tamara] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
[Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
[Rosano, Caterina] Univ Pittsburgh, Dept Epidemiol, Ctr Aging & Populat Hlth, Pittsburgh, PA 15261 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA.
RP Nettiksimmons, J (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
EM Jasmine.nettiksimmons@ucsf.edu
OI Rosano, Caterina/0000-0002-0909-1506; Rosano,
Caterina/0000-0002-4271-6010
FU NIA [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; NINR
[R01-NR012459]; Intramural Research Program of the NIH, National
Institute of Aging; American Health Assistance Foundation [A201-0029];
National Institute of Aging [K24AG031155]
FX This research was supported by the following: NIA contract numbers:
N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106; NIA grant numbers:
R01-AG028050, NINR grant R01-NR012459. This research was supported in
part by the Intramural Research Program of the NIH, National Institute
of Aging and by a grant from the American Health Assistance Foundation,
grant number A201-0029. Dr. Yaffe is supported in part by a National
Institute of Aging Grant (K24AG031155). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 35
TC 16
Z9 17
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 26
PY 2014
VL 9
IS 3
AR e91339
DI 10.1371/journal.pone.0091339
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE0SR
UT WOS:000333677000018
PM 24670553
ER
PT J
AU Wang, J
Land, D
Ono, K
Galvez, J
Zhao, W
Vempati, P
Steele, JW
Cheng, A
Yamada, M
Levine, S
Mazzola, P
Pasinetti, GM
AF Wang, Jun
Land, David
Ono, Kenjiro
Galvez, Jorge
Zhao, Wei
Vempati, Prashant
Steele, John W.
Cheng, Alice
Yamada, Masahito
Levine, Samara
Mazzola, Paolo
Pasinetti, Giulio M.
TI Molecular Topology as Novel Strategy for Discovery of Drugs with A beta
Lowering and Anti-Aggregation Dual Activities for Alzheimer's Disease
SO PLOS ONE
LA English
DT Article
ID MOUSE MODEL; PROTEIN; OLIGOMERS; NEUROPATHOLOGY; TOXICITY; PATHWAY;
DESIGN; MEMORY
AB Background and Purpose: In this study, we demonstrate the use of Molecular topology (MT) in an Alzheimer's disease (AD) drug discovery program. MT uses and expands upon the principles governing the molecular connectivity theory of numerically characterizing molecular structures, in the present case, active anti-AD drugs/agents, using topological descriptors to build models. Topological characterization has been shown to embody sufficient molecular information to provide strong correlation to therapeutic efficacy.
Experimental Approach: We used MT to include multiple bioactive properties that allows for the identification of multifunctional single agent compounds, in this case, the dual functions of beta-amyloid (A beta) -lowering and anti-oligomerization. Using this technology, we identified and designed novel compounds in chemical classes unrelated to current anti-AD agents that exert dual A beta lowering and anti-A beta oligomerization activities in animal models of AD. AD is a multifaceted disease with different pathological features.
Conclusion and Implications: Our study, for the first time, demonstrated that MT can provide novel strategy for discovering drugs with A beta lowering and anti-aggregation dual activities for AD.
C1 [Wang, Jun; Zhao, Wei; Vempati, Prashant; Steele, John W.; Cheng, Alice; Levine, Samara; Mazzola, Paolo; Pasinetti, Giulio M.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA.
[Land, David] Medisyn Technol Inc, Minnetonka, MN USA.
[Ono, Kenjiro; Yamada, Masahito] Kanazawa Univ, Dept Neurol & Neurobiol Aging, Kanazawa, Ishikawa, Japan.
[Galvez, Jorge] Univ Valencia, Mol Topol & Drug Design Unit, Valencia, Spain.
[Wang, Jun; Pasinetti, Giulio M.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA.
RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA.
EM giulio.pasinetti@mssm.edu
FU Altschul Foundation; Icahn School of Medicine at Mount Sinai
FX This study is supported in part by the Altschul Foundation and by
Discretionary Funds to Giulio Maria Pasinetti from the Icahn School of
Medicine at Mount Sinai.
NR 33
TC 0
Z9 0
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 26
PY 2014
VL 9
IS 3
AR e92750
DI 10.1371/journal.pone.0092750
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE0SR
UT WOS:000333677000072
PM 24671215
ER
PT J
AU Goldberg, DS
French, B
Forde, KA
Groeneveld, PW
Bittermann, T
Backus, L
Halpern, SD
Kaplan, DE
AF Goldberg, David S.
French, Benjamin
Forde, Kimberly A.
Groeneveld, Peter W.
Bittermann, Therese
Backus, Lisa
Halpern, Scott D.
Kaplan, David E.
TI Association of Distance From a Transplant Center With Access to Waitlist
Placement, Receipt of Liver Transplantation, and Survival Among US
Veterans
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID HEPATITIS-C VIRUS; BARIATRIC SURGERY; UNITED-STATES; PRIMARY-CARE;
SERVICES; POLICY; MODEL; IMPLEMENTATION; EXCELLENCE; GUIDELINES
AB IMPORTANCE Centralization of specialized health care services such as organ transplantation and bariatric surgery is advocated to improve quality, increase efficiency, and reduce cost. The effect of increased travel on access and outcomes from these services is not fully understood.
OBJECTIVE To evaluate the association between distance from a Veterans Affairs (VA) transplant center (VATC) and access to being waitlisted for liver transplantation, actually having a liver transplant, and mortality.
DESIGN, SETTING, AND PARTICIPANTS Retrospective study of veterans meeting liver transplantation eligibility criteria from January 1, 2003, until December 31, 2010, using data from the Veterans Health Administration's integrated, national, electronic medical record linked to Organ Procurement and Transplantation Network data.
MAIN OUTCOMES AND MEASURES The primary outcome was being waitlisted for transplantation at a VATC. Secondary outcomes included being waitlisted at any transplant center, undergoing a transplantation, and survival.
RESULTS From 2003-2010, 50 637 veterans were classified as potentially eligible for transplant; 2895 (6%) were waitlisted and 1418 of those were waitlisted (49%) at 1 of the 5 VATCs. Of 3417 veterans receiving care at a VA hospital located within 100 miles from a VATC, 244 (7.1%) were waitlisted at a VATC and 372 (10.9%) at any transplant center (VATC and non-VATCs). Of 47 219 veterans receiving care at a VA hospital located more than 100 miles from a VATC, 1174 (2.5%) were waitlisted at a VATC and 2523 (5.3%) at any transplant center (VATC and non-VATCs). In multivariable models, increasing distance to closest VATC was associated with significantly lower odds of being waitlisted at a VATC (odds ratio [OR], 0.91 [95% CI, 0.89-0.93] for each doubling in distance) or any transplant center (OR, 0.94 [95% CI, 0.92-0.96] for each doubling in distance). For example, a veteran living 25 miles from a VATC would have a 7.4%(95% CI, 6.6%-8.1%) adjusted probability of being waitlisted, whereas a veteran 100 miles from a VATC would have a 6.2%(95% CI, 5.7%-6.6%) adjusted probability. In adjusted models, increasing distance from a VATC was associated with significantly lower transplantation rates (subhazard ratio, 0.97; 95% CI, 0.95-0.98 for each doubling in distance). There was significantly increased mortality among waitlisted veterans from the time of first hepatic decompensation event in multivariable survival models (hazard ratio, 1.03; 95% CI, 1.01-1.04 for each doubling in distance). For example, a waitlisted veteran living 25 miles from a VATC would have a 62.9% (95% CI, 59.1%-66.1%) 5-year adjusted probability of survival from first hepatic decompensation event compared with a 59.8%(95% CI, 56.3%-63.1%) 5-year adjusted probability of survival for a veteran living 100 miles from a VATC.
CONCLUSIONS AND RELEVANCE Among VA patients meeting eligibility criteria for liver transplantation, greater distance from a VATC or any transplant center was associated with lower likelihood of being waitlisted, receiving a liver transplant, and greater likelihood of death. The relationship between these findings and centralizing specialized care deserves further investigation.
C1 [Goldberg, David S.; Forde, Kimberly A.; Kaplan, David E.] Univ Penn, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA.
[Goldberg, David S.; French, Benjamin; Forde, Kimberly A.; Halpern, Scott D.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Goldberg, David S.; French, Benjamin; Groeneveld, Peter W.; Halpern, Scott D.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA.
[Groeneveld, Peter W.] Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA.
[Groeneveld, Peter W.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
[Bittermann, Therese] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Backus, Lisa] Dept Vet Affairs, Off Publ Hlth, Philadelphia, PA USA.
[Halpern, Scott D.] Univ Penn, Dept Med, Div Pulm Allergy & Crit Care, Philadelphia, PA 19104 USA.
[Kaplan, David E.] Philadelphia VA Med Ctr, Gastroenterol Sect, Philadelphia, PA USA.
RP Goldberg, DS (reprint author), Hosp Univ Penn, 3400 Civ Ctr Blvd,9 Penn Tower, Philadelphia, PA 19104 USA.
EM david.goldberg@uphs.upenn.edu
FU Health Resources and Services Administration [234-2005-37011C]
FX This work was supported in part by Health Resources and Services
Administration contract 234-2005-37011C.
NR 40
TC 24
Z9 24
U1 3
U2 4
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAR 26
PY 2014
VL 311
IS 12
BP 1234
EP 1243
DI 10.1001/jama.2014.2520
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA AD6CE
UT WOS:000333340500027
PM 24668105
ER
PT J
AU McNulty, EJ
Hung, YY
Almers, LM
Go, AS
Yeh, RW
AF McNulty, Edward J.
Hung, Yun-Yi
Almers, Lucy M.
Go, Alan S.
Yeh, Robert W.
TI Population Trends From 2000-2011 in Nuclear Myocardial Perfusion Imaging
Use
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
ID UNITED-STATES
C1 [McNulty, Edward J.] Kaiser Permanente Med Ctr, Div Cardiol, San Francisco, CA 94115 USA.
[Hung, Yun-Yi; Almers, Lucy M.; Go, Alan S.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Yeh, Robert W.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
RP McNulty, EJ (reprint author), Kaiser Permanente Med Ctr, 2200 OFarrell Blvd, San Francisco, CA 94115 USA.
EM edward.j.mcnulty@kp.org
NR 5
TC 12
Z9 12
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAR 26
PY 2014
VL 311
IS 12
BP 1248
EP 1249
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA AD6CE
UT WOS:000333340500030
PM 24668108
ER
PT J
AU Liberman, MC
Liberman, LD
Maison, SF
AF Liberman, M. Charles
Liberman, Leslie D.
Maison, Stephane F.
TI Efferent Feedback Slows Cochlear Aging
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE auditory neuropathy; feedback; hair cells; hearing conservation
ID AUDITORY-NERVE FIBERS; CROSSED OLIVOCOCHLEAR BUNDLE; GUINEA-PIG COCHLEA;
ELECTRICAL-STIMULATION; MAMMALIAN COCHLEA; ACOUSTIC INJURY;
HEARING-LOSS; BRAIN-STEM; OTOACOUSTIC EMISSIONS; SYNAPTIC RIBBONS
AB The inner ear receives two types of efferent feedback from the brainstem: one pathway provides gain control on outer hair cells' contribution to cochlear amplification, and the other modulates the excitability of the cochlear nerve. Although efferent feedback can protect hair cells from acoustic injury and thereby minimize noise-induced permanent threshold shifts, most prior studies focused on high-intensity exposures (> 100 dB SPL). Here, we show that efferents are essential for long-term maintenance of cochlear function in mice aged 1 year post-de-efferentation without purposeful acoustic overexposure. Cochlear de-efferentation was achieved by surgical lesion of efferent pathways in the brainstem and was assessed by quantitative analysis of immunostained efferent terminals in outer and inner hair cell areas. The resultant loss of efferent feedback accelerated the age-related amplitude reduction in cochlear neural responses, as seen in auditory brainstem responses, and increased the loss of synapses between hair cells and the terminals of cochlear nerve fibers, as seen in confocal analysis of the organ of Corti immunostained for presynaptic and postsynaptic markers. This type of neuropathy, also seen after moderate noise exposure, has been termed "hidden hearing loss", because it does not affect thresholds, but can be seen in the suprathreshold amplitudes of cochlear neural responses, and likely causes problems with hearing in a noisy environment, a classic symptom of age-related hearing loss in humans. Since efferent reflex strength varies among individuals and can be measured noninvasively, a weak reflex may be an important risk factor, and prognostic indicator, for age-related hearing impairment.
C1 [Liberman, M. Charles; Maison, Stephane F.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA.
[Liberman, M. Charles; Liberman, Leslie D.; Maison, Stephane F.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA.
[Liberman, M. Charles; Maison, Stephane F.] Harvard Program Speech & Hearing Biosci & Technol, Boston, MA 02114 USA.
RP Maison, SF (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA.
EM stephane_maison@meei.harvard.edu
FU National Institute on Deafness and Other Communication Disorders [R01 DC
0188, P30 DC 05209]
FX Research was supported by National Institute on Deafness and Other
Communication Disorders Grants R01 DC 0188 and P30 DC 05209.
NR 59
TC 33
Z9 34
U1 2
U2 25
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAR 26
PY 2014
VL 34
IS 13
BP 4599
EP 4607
DI 10.1523/JNEUROSCI.4923-13.2014
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA AE0RP
UT WOS:000333674200016
PM 24672005
ER
PT J
AU Fang, MC
Go, AS
Chang, YC
Borowsky, LH
Pomernacki, NK
Udaltsova, N
Singer, DE
AF Fang, Margaret C.
Go, Alan S.
Chang, Yuchiao
Borowsky, Leila H.
Pomernacki, Niela K.
Udaltsova, Natalia
Singer, Daniel E.
TI Long-term survival after ischemic stroke in patients with atrial
fibrillation
SO NEUROLOGY
LA English
DT Article
ID ANTICOAGULATION THERAPY; ANTITHROMBOTIC THERAPY; RISK-FACTORS;
MORTALITY; WARFARIN; REGISTRY; POPULATION; PREVENTION; SEVERITY; PROJECT
AB Objectives:While the short-term impact of atrial fibrillation-related stroke has been well studied, surprisingly little is known about its long-term effect on survival.Methods:We followed 13,559 patients with atrial fibrillation for a median of 6 years, identifying ischemic strokes through computerized databases and validating 1,025 events. Stroke severity was determined from hospital records. We compared survival of stroke patients with comparator nonstroke patients (matched for age, sex, race, comorbid conditions, and time of entry into the cohort) using proportional hazard models controlling for warfarin use and compared survival by degree of discharge deficit.Results:Median survival after stroke was 1.8 years compared with 5.7 years for matched nonstroke comparators (hazard ratio [HR] 2.8, 95% confidence interval [CI] 2.5-3.2). This increased risk of all-cause death persisted even after restricting the analysis to the 576 stroke patients who survived 6 months after the initial stroke event (HR 2.0, 95% CI 1.7-2.5, adjusting for warfarin use). Risk of death was strongly associated with stroke severity: HR 2.9 (95% CI 2.3-3.5) for strokes resulting in major deficits and HR 8.3 (95% CI 5.2-13.2) for strokes resulting in severe deficits compared with matched comparators without stroke.Conclusions:Ischemic stroke approximately triples the mortality rate in patients with atrial fibrillation. This effect persists well beyond the immediate period poststroke and is strongly associated with disability after stroke. Stroke prevention by anticoagulation has even greater beneficial effects on survival than usually considered when focusing solely on 30-day mortality rates.
C1 [Fang, Margaret C.; Go, Alan S.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Go, Alan S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Go, Alan S.; Pomernacki, Niela K.; Udaltsova, Natalia] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Chang, Yuchiao; Borowsky, Leila H.; Singer, Daniel E.] Massachusetts Gen Hosp, Clin Epidemiol Unit, Div Gen Med, Boston, MA 02114 USA.
RP Fang, MC (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
EM mfang@medicine.ucsf.edu
FU National Institute on Aging [R01 AG15478, K23 AG028978]; National Heart,
Lung, and Blood Institute [U19 HL91179, RC2HL101589]; Eliot B. and Edith
C. Shoolman fund of the Massachusetts General Hospital (Boston)
FX Supported by the National Institute on Aging (R01 AG15478 and K23
AG028978), the National Heart, Lung, and Blood Institute (U19 HL91179
and RC2HL101589), and the Eliot B. and Edith C. Shoolman fund of the
Massachusetts General Hospital (Boston). The funding sources had no role
in study design, data collection, data analysis, data interpretation, or
preparation of the manuscript. Dr. Fang had full access to all of the
data in the study and takes responsibility for the integrity of the data
and the accuracy of the data analysis.
NR 26
TC 8
Z9 8
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD MAR 25
PY 2014
VL 82
IS 12
BP 1033
EP 1037
DI 10.1212/WNL.0000000000000248
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA AH9XW
UT WOS:000336500100010
PM 24532273
ER
PT J
AU James, BD
Leurgans, SE
Hebert, LE
Scherr, PA
Yaffe, K
Bennett, DA
AF James, Bryan D.
Leurgans, Sue E.
Hebert, Liesi E.
Scherr, Paul A.
Yaffe, Kristine
Bennett, David A.
TI Contribution of Alzheimer disease to mortality in the United States
SO NEUROLOGY
LA English
DT Article
ID MILD COGNITIVE IMPAIRMENT; COMMUNITY-BASED COHORT; CLINICAL-DIAGNOSIS;
AGING PROJECT; OLDER PERSONS; RUSH MEMORY; DEMENTIA; SURVIVAL; DEATH;
POPULATION
AB Objective:To assess the burden of mortality attributable to Alzheimer disease (AD) dementia in the United States.Methods:Data came from 2,566 persons aged 65 years and older (mean 78.1 years) without dementia at baseline from 2 cohort studies of aging with identical annual diagnostic assessments of dementia. Because both studies require organ donation, ascertainment of mortality was complete and dates of death accurate. Mortality hazard ratios (HRs) after incident AD dementia were estimated per 10-year age strata from proportional hazards models. Population attributable risk percentage was derived to estimate excess mortality after a diagnosis of AD dementia. The number of excess deaths attributable to AD dementia in the United States was then estimated.Results:Over an average of 8 years, 559 participants (21.8%) without dementia at baseline developed AD dementia and 1,090 (42.4%) died. Median time from AD dementia diagnosis to death was 3.8 years. The mortality HR for AD dementia was 4.30 (confidence interval = 3.33, 5.58) for ages 75-84 years and 2.77 (confidence interval = 2.37, 3.23) for ages 85 years and older (too few deaths after AD dementia in ages 65-74 were available to estimate HR). Population attributable risk percentage was 37.0% for ages 75-84 and 35.8% for ages 85 and older. An estimated 503,400 deaths in Americans aged 75 years and older were attributable to AD dementia in 2010.Conclusions:A larger number of deaths are attributable to AD dementia in the United States each year than the number (<84,000 in 2010) reported on death certificates.
C1 [James, Bryan D.; Leurgans, Sue E.; Bennett, David A.] Rush Univ, Rush Alzheimers Dis Ctr, Med Ctr, Chicago, IL 60612 USA.
[James, Bryan D.] Rush Univ, Dept Internal Med, Med Ctr, Chicago, IL 60612 USA.
[Leurgans, Sue E.; Bennett, David A.] Rush Univ, Dept Neurol Sci, Med Ctr, Chicago, IL 60612 USA.
[Hebert, Liesi E.; Scherr, Paul A.] Rush Univ, Rush Inst Hlth Aging, Med Ctr, Chicago, IL 60612 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA.
[Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA.
RP James, BD (reprint author), Rush Univ, Rush Alzheimers Dis Ctr, Med Ctr, Chicago, IL 60612 USA.
EM Bryan_James@rush.edu
FU National Institute on Aging [P30 AG10161, R01AG15819, R01AG17917,
K24AG031155]; Illinois Department of Public Health [23282007]
FX Directly supported by the National Institute on Aging (P30 AG10161,
R01AG15819, R01AG17917, K24AG031155), and the Illinois Department of
Public Health (contract 23282007).
NR 35
TC 50
Z9 51
U1 1
U2 16
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD MAR 25
PY 2014
VL 82
IS 12
BP 1045
EP 1050
DI 10.1212/WNL.0000000000000240
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA AH9XW
UT WOS:000336500100012
PM 24598707
ER
PT J
AU Lu, L
Barfejani, AH
Qin, T
Dong, Q
Ayata, C
Waeber, C
AF Lu, Lei
Barfejani, Arnavaz Hajizadeh
Qin, Tao
Dong, Qiang
Ayata, Cenk
Waeber, Christian
TI Fingolimod exerts neuroprotective effects in a mouse model of
intracerebral hemorrhage
SO BRAIN RESEARCH
LA English
DT Article
DE Intracerebral hemorrhage; Stroke; FTY720; Sphingosine 1-phosphate;
Neuroprotection
ID CEREBRAL-ARTERY OCCLUSION; SPHINGOSINE 1-PHOSPHATE RECEPTOR-1; TRAUMATIC
BRAIN-INJURY; MULTIPLE-SCLEROSIS; FTY720 FINGOLIMOD; IN-VIVO; RATS;
STROKE; REMYELINATION; APOPTOSIS
AB Recent studies have shown that fingolimod (FTY720) is neuroprotective in CNS injury models of cerebral ischemia and spinal cord injury. The purpose of the study was to examine the effect of fingolimod in a mouse model of intracerebral hemorrhage. ICH was produced in adult CD1 mice by injecting collagenase VII-S (0.5 mu L, 0.06 U) into the basal ganglia. Fingolimod (or saline) was given 30 min after surgery and once daily for two days. Three days after intracerebral hemorrhage, brain edema, hematoma volume and the number of apoptotic cells were quantified. In another cohort of mice, brain atrophy was evaluated two weeks following intracerebral hemorrhage. Neurobehavioral tests were performed on the 3rd, the 7th and the 14th day. Fingolimod significantly decreased edema, apoptosis and brain atrophy. More importantly, fingolimod enhanced neurobehavioral recovery. Preliminary experiments showed no difference in the number of inflammatory (CD68-positive) cells between the two groups. In conclusion, fingolimod exerts protective effects in a mouse model of intracerebral hemorrhage; the mechanisms underlying these neuroprotective effects deserve further study. (c) 2014 Elsevier B.V. All rights reserved.
C1 [Lu, Lei; Barfejani, Arnavaz Hajizadeh; Qin, Tao; Waeber, Christian] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA.
[Barfejani, Arnavaz Hajizadeh] Northeastern Univ, Sch Pharm, Bouve Coll Hlth Sci, Boston, MA 02115 USA.
[Dong, Qiang] Fudan Univ, Huashan Hosp, Dept Neurol, State Key Lab Med Neurobiol, Shanghai 200040, Peoples R China.
[Ayata, Cenk] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA.
RP Waeber, C (reprint author), Natl Univ Ireland Univ Coll Cork, Sch Pharm, Cavanagh Bldg,Room 1-26,Coll Rd, Cork, Ireland.
EM c.waeber@ucc.ie
RI Waeber, Christian/A-8333-2009
OI Waeber, Christian/0000-0001-6078-0027
FU NIH [NS049263, NS055104]; Boehringer Ingelheim Pharma GmbH Co. KG
FX Funding for this study was provided by NIH Grant nos. (NS049263 and
NS055104 to Dr. Christian Waeber). We thank Prof. Wolfgang Eisert and
Boehringer Ingelheim Pharma GmbH & Co. KG for providing the BI Stroke
Award fellowship to Dr. Lei Lu. We thank Prof. Eng H. Lo for his
critical advice and support during the study.
NR 40
TC 18
Z9 18
U1 1
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
EI 1872-6240
J9 BRAIN RES
JI Brain Res.
PD MAR 25
PY 2014
VL 1555
BP 89
EP 96
DI 10.1016/j.brainres.2014.01.048
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA AF1LS
UT WOS:000334476000009
PM 24502984
ER
PT J
AU Brown, ST
Tate, JP
Kyriakides, TC
Kirkwood, KA
Holodniy, M
Goulet, JL
Angus, BJ
Cameron, DW
Justice, AC
AF Brown, Sheldon T.
Tate, Janet P.
Kyriakides, Tassos C.
Kirkwood, Katherine A.
Holodniy, Mark
Goulet, Joseph L.
Angus, Brian J.
Cameron, D. William
Justice, Amy C.
CA OPTIMA Team
TI The VACS Index Accurately Predicts Mortality and Treatment Response
among Multi-Drug Resistant HIV Infected Patients Participating in the
Options in Management with Antiretrovirals (OPTIMA) Study
SO PLOS ONE
LA English
DT Article
ID VETERANS AGING COHORT; NON-AIDS EVENTS; NONFATAL AIDS; RISK; THERAPY;
PROGRESSION; EFFICACY; DISEASE; TRIALS; SAFETY
AB Objectives: The VACS Index is highly predictive of all-cause mortality among HIV infected individuals within the first few years of combination antiretroviral therapy (cART). However, its accuracy among highly treatment experienced individuals and its responsiveness to treatment interventions have yet to be evaluated. We compared the accuracy and responsiveness of the VACS Index with a Restricted Index of age and traditional HIV biomarkers among patients enrolled in the OPTIMA study.
Methods: Using data from 324/339 (96%) patients in OPTIMA, we evaluated associations between indices and mortality using Kaplan-Meier estimates, proportional hazards models, Harrel's C-statistic and net reclassification improvement (NRI). We also determined the association between study interventions and risk scores over time, and change in score and mortality.
Results: Both the Restricted Index (c = 0.70) and VACS Index (c = 0.74) predicted mortality from baseline, but discrimination was improved with the VACS Index (NRI = 23%). Change in score from baseline to 48 weeks was more strongly associated with survival for the VACS Index than the Restricted Index with respective hazard ratios of 0.26 (95% CI 0.14-0.49) and 0.39(95% CI 0.22-0.70) among the 25% most improved scores, and 2.08 (95% CI 1.27-3.38) and 1.51 (95% CI 0.90-2.53) for the 25% least improved scores.
Conclusions: The VACS Index predicts all-cause mortality more accurately among multi-drug resistant, treatment experienced individuals and is more responsive to changes in risk associated with treatment intervention than an index restricted to age and HIV biomarkers. The VACS Index holds promise as an intermediate outcome for intervention research.
C1 [Brown, Sheldon T.] James J Peters VA Med Ctr, Bronx, NY 10468 USA.
[Brown, Sheldon T.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY USA.
[Tate, Janet P.; Goulet, Joseph L.; Justice, Amy C.] VA Connecticut Healthcare Syst, Gen Internal Med Sect, West Haven, CT USA.
[Tate, Janet P.; Goulet, Joseph L.; Justice, Amy C.] Yale Univ, Sch Med, New Haven, CT USA.
[Tate, Janet P.; Goulet, Joseph L.; Justice, Amy C.] Yale Univ, Sch Publ Hlth, New Haven, CT USA.
[Kyriakides, Tassos C.; Kirkwood, Katherine A.] VA Connecticut Healthcare Syst, VA Cooperat Studies Program, Coordinating Ctr, West Haven, CT USA.
[Holodniy, Mark] VA Palo Alto Healthcare Syst, Palo Alto, CA USA.
[Holodniy, Mark] Stanford Univ, Sch Med, Dept Med, Palo Alto, CA 94304 USA.
[Angus, Brian J.] Univ Oxford, Nuffield Dept Med, Oxford, England.
[Cameron, D. William] Univ Ottawa, Ottawa Hosp, Res Inst, Ottawa, ON, Canada.
RP Brown, ST (reprint author), James J Peters VA Med Ctr, Bronx, NY 10468 USA.
EM sheldon.brown@va.gov
OI Cameron, Bill/0000-0002-0090-3539; Goulet, Joseph/0000-0002-0842-804X
FU Office of Research and Development (Cooperative Studies Program), US
Department of Veterans Affairs; US National Institutes of Health,
National Institute on Alcohol Abuse and Alcoholism [U01-13566]; Canadian
Institutes for Health Research; United Kingdom Medical Research Council;
Ontario HIV Treatment Network/Ministry of Health, Canada
FX This work was supported by the Office of Research and Development
(Cooperative Studies Program), US Department of Veterans Affairs; US
National Institutes of Health, National Institute on Alcohol Abuse and
Alcoholism [U01-13566]; Canadian Institutes for Health Research; and
United Kingdom Medical Research Council. DWC is a Career Scientist
supported by the Ontario HIV Treatment Network/Ministry of Health,
Canada. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 25
TC 5
Z9 5
U1 2
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 25
PY 2014
VL 9
IS 3
AR e92606
DI 10.1371/journal.pone.0092606
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE0SD
UT WOS:000333675600053
PM 24667813
ER
PT J
AU Codeluppi, S
Fernandez-Zafra, T
Sandor, K
Kjell, J
Liu, QS
Abrams, M
Olson, L
Gray, NS
Svensson, CI
Uhlen, P
AF Codeluppi, Simone
Fernandez-Zafra, Teresa
Sandor, Katalin
Kjell, Jacob
Liu, Qingsong
Abrams, Mathew
Olson, Lars
Gray, Nathanael S.
Svensson, Camilla I.
Uhlen, Per
TI Interleukin-6 Secretion by Astrocytes Is Dynamically Regulated by
PI3K-mTOR-Calcium Signaling
SO PLOS ONE
LA English
DT Article
ID SPINAL-CORD-INJURY; GENE-EXPRESSION; MESSENGER-RNA; IMMUNE-RESPONSES;
SMOOTH-MUSCLE; CNS REPAIR; GLIAL SCAR; MTOR; REGENERATION; RAPAMYCIN
AB After contusion spinal cord injury (SCI), astrocytes become reactive and form a glial scar. While this reduces spreading of the damage by containing the area of injury, it inhibits regeneration. One strategy to improve the recovery after SCI is therefore to reduce the inhibitory effect of the scar, once the acute phase of the injury has passed. The pleiotropic cytokine interleukin-6 (IL-6) is secreted immediately after injury and regulates scar formation; however, little is known about the role of IL-6 in the sub-acute phases of SCI. Interestingly, IL-6 also promotes axon regeneration, and therefore its induction in reactive astrocytes may improve regeneration after SCI. We found that IL-6 is expressed by astrocytes and neurons one week post-injury and then declines. Using primary cultures of rat astrocytes we delineated the molecular mechanisms that regulate IL-6 expression and secretion. IL-6 expression requires activation of p38 and depends on NF-kappa B transcriptional activity. Activation of these pathways in astrocytes occurs when the PI3K-mTOR-AKT pathway is inhibited. Furthermore, we found that an increase in cytosolic calcium concentration was necessary for IL-6 secretion. To induce IL-6 secretion in astrocytes, we used torin2 and rapamycin to block the PI3K-mTOR pathway and increase cytosolic calcium, respectively. Treating injured animals with torin2 and rapamycin for two weeks, starting two weeks after injury when the scar has been formed, lead to a modest effect on mechanical hypersensitivity, limited to the period of treatment. These data, taken together, suggest that treatment with torin2 and rapamycin induces IL-6 secretion by astrocytes and may contribute to the reduction of mechanical hypersensitivity after SCI.
C1 [Codeluppi, Simone; Fernandez-Zafra, Teresa; Uhlen, Per] Karolinska Inst, Mol Neurobiol Lab, Dept Med Biochem & Biophys, Stockholm, Sweden.
[Sandor, Katalin; Svensson, Camilla I.] Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
[Kjell, Jacob; Abrams, Mathew; Olson, Lars] Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
[Liu, Qingsong; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Liu, Qingsong; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
RP Codeluppi, S (reprint author), Karolinska Inst, Mol Neurobiol Lab, Dept Med Biochem & Biophys, Stockholm, Sweden.
EM simone.codeluppi@ki.se
RI codeluppi, simone/I-4143-2012;
OI codeluppi, simone/0000-0002-7053-0520; Kjell, Jacob/0000-0002-8335-0780;
Uhlen, Per/0000-0003-1446-1062
FU Wenner-Gren foundation; Svenska Sallskapet for Medicinsk Forskning;
Becas Talentia; Hjarnfonden; Swedish Research Council; Linnaeus Center
in Developmental Biology for Regenerative Medicine; Knut and Alice
Wallenberg Foundation; Royal Swedish Academy of Sciences; Wings for
Life; Vinnova; Karolinska Distinguished Professor Award; Karolinska
StratNeuro program
FX This work was supported by: Wenner-Gren foundation (SC, KS), Svenska
Sallskapet for Medicinsk Forskning (SC), Becas Talentia (TFZ),
Hjarnfonden (SC, PU), Swedish Research Council (CS, PU, LO), Linnaeus
Center in Developmental Biology for Regenerative Medicine (PU), the Knut
and Alice Wallenberg Foundation Grant to Center of Live Imaging of Cells
at Karolinska Institutet (PU), the Royal Swedish Academy of Sciences
(PU), Wings for Life (LO, MA), Vinnova (LO), Karolinska Distinguished
Professor Award (LO), Karolinska StratNeuro program (LO). The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 56
TC 3
Z9 5
U1 2
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 25
PY 2014
VL 9
IS 3
AR e92649
DI 10.1371/journal.pone.0092649
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE0SD
UT WOS:000333675600061
PM 24667246
ER
PT J
AU Jamin, Y
Glass, L
Hallsworth, A
George, R
Koh, DM
Pearson, ADJ
Chesler, L
Robinson, SP
AF Jamin, Yann
Glass, Laura
Hallsworth, Albert
George, Rani
Koh, Dow-Mu
Pearson, Andrew D. J.
Chesler, Louis
Robinson, Simon P.
TI Intrinsic Susceptibility MRI Identifies Tumors with ALK(F1174L) Mutation
in Genetically-Engineered Murine Models of High-Risk Neuroblastoma
SO PLOS ONE
LA English
DT Article
ID VASCULAR ARCHITECTURE; ACTIVATING MUTATIONS; ALK KINASE; CANCER; MYCN;
ANGIOGENESIS; HYPOXIA; IMMUNOHISTOCHEMISTRY; AMPLIFICATION; RECRUITMENT
AB The early identification of children presenting ALK(F1174L)-mutated neuroblastoma, which are associated with resistance to the promising ALK inhibitor crizotinib and a marked poorer prognosis, has become a clinical priority. In comparing the radiology of the novel Th-ALK(F1174L)/Th-MYCN and the well-established Th-MYCN genetically-engineered murine models of neuroblastoma using MRI, we have identified a marked ALK(F1174L)-driven vascular phenotype. We demonstrate that quantitation of the transverse relaxation rate R-2* (s(-1)) using intrinsic susceptibility-MRI under baseline conditions and during hyperoxia, can robustly discriminate this differential vascular phenotype, and identify MYCN-driven tumors harboring the ALK(F1174L) mutation with high specificity and selectivity. Intrinsic susceptibility-MRI could thus potentially provide a non-invasive and clinically-exploitable method to help identifying children with MYCN-driven neuroblastoma harboring the ALK(F1174L) mutation at the time of diagnosis.
C1 [Jamin, Yann; Glass, Laura; Koh, Dow-Mu; Chesler, Louis; Robinson, Simon P.] Inst Canc Res, Div Radiotherapy & Imaging, London SW3 6JB, England.
[Jamin, Yann; Glass, Laura; Koh, Dow-Mu; Chesler, Louis; Robinson, Simon P.] Royal Marsden NHS Fdn Trust, London, England.
[Glass, Laura; Hallsworth, Albert; Chesler, Louis] Inst Canc Res, Div Canc Therapeut, London SW3 6JB, England.
[Glass, Laura; Chesler, Louis] Inst Canc Res, Div Mol Pathol, London SW3 6JB, England.
[Glass, Laura; Pearson, Andrew D. J.; Chesler, Louis] Inst Canc Res, Div Clin Studies, London SW3 6JB, England.
[George, Rani] Dana Farber Canc Inst, Dept Pediat Haematol & Oncol, Boston, MA 02115 USA.
[George, Rani] Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA.
RP Jamin, Y (reprint author), Inst Canc Res, Div Radiotherapy & Imaging, London SW3 6JB, England.
EM yann.jamin@icr.ac.uk
FU Institute of Cancer Research CR-UK; EPSRC Cancer Imaging Centre; MRC;
Department of Health (England) [C1060/A10334]; NHS; Cancer Research-UK
project grants [C16412/A6269]; Wellcome Trust [091763Z/10/Z]; Medical
Research Council [G1000391]; Neuroblastoma Society; SPARKS charity;
Medical Research Council NC3R [G1000121/94513]; National Institutes of
Health [R01 CA148688]
FX The authors acknowledge support received for The Institute of Cancer
Research CR-UK (http://www.cancerresearchuk.org/) and EPSRC
(http://www.epsrc.ac.uk) Cancer Imaging Centre, in association with the
MRC (http://www.epsrc.ac.uk) and Department of Health (England)
(https://www.gov.uk/government/organisations/department-of-health) grant
C1060/A10334, and NHS funding to the NIHR Biomedical Research Centre.
This work was supported by Cancer Research-UK project grants
C16412/A6269, The Wellcome Trust (grant #091763Z/10/Z)
(http://www.wellcome.ac.uk), and the Medical Research Council (grant
#G1000391). Pre-clinical development of the TH-ALKF1174L/TH-MYCN model
was funded by grants from The Neuroblastoma Society
(http://www.nsoc.co.uk), the SPARKS charity (http://www.sparks.org.uk),
Medical Research Council NC3R (grant
#G1000121/94513)(http://www.nc3rs.org.uk/), and the National Institutes
of Health (R01 CA148688) (http://www.nih.gov). The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 35
TC 4
Z9 4
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 25
PY 2014
VL 9
IS 3
AR e92886
DI 10.1371/journal.pone.0092886
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE0SD
UT WOS:000333675600099
PM 24667968
ER
PT J
AU Kiwanuka, J
Mulogo, E
Haberer, JE
AF Kiwanuka, Julius
Mulogo, Edgar
Haberer, Jessica E.
TI Caregiver Perceptions and Motivation for Disclosing or Concealing the
Diagnosis of HIV Infection to Children Receiving HIV Care in Mbarara,
Uganda: A Qualitative Study
SO PLOS ONE
LA English
DT Article
ID SCHOOL-AGE-CHILDREN; SOUTH-AFRICA; ADOLESCENTS; HIV/AIDS; MORTALITY;
MOTHERS; HEALTH
AB Background: Disclosure of the diagnosis of HIV to HIV-infected children is challenging for caregivers. Despite current recommendations, data suggest that levels of disclosure of HIV status to HIV-infected children receiving care in resource-limited settings are very low. Few studies describe the disclosure process for children in these settings, particularly the motivators, antecedent goals, and immediate outcomes of disclosure to HIV-infected children. This study examined caregivers' perception of the disclosure concept prior to disclosure, their motivation towards or away from disclosure, and their short-and long-term intentions for disclosure to their HIV-infected children.
Methods: In-depth interviews were conducted with primary caregivers of 40 HIV-infected children (ages 5-15 years) who were receiving HIV care but did not know their HIV status.
Results: Caregivers of HIV-infected children mainly perceived disclosure as a single event rather than a process of gradual delivery of information about the child's illness. They viewed disclosure as potentially beneficial both to children and themselves, as well as an opportunity to explain the parents' role in the transmission of HIV to the children. Caregivers desired to personally conduct the disclosure; however, most reported being over-whelmed with fear of negative outcomes and revealed a lack of self-efficacy towards managing the disclosure process. Consequently, most cope by deception to avoid or delay disclosure until they perceive their own readiness to disclose.
Conclusions: Interventions for HIV disclosure should consider that caregivers may desire to be directly responsible for disclosure to children under their care. They, however, need to be empowered with practical skills to recognize opportunities to initiate the disclosure process early, as well as supported to manage it in a phased, developmentally appropriate manner. The potential role for peer counselors in the disclosure process deserves further study.
C1 [Kiwanuka, Julius] Mbarara Univ Sci & Technol, Dept Paediat & Child Hlth, Mbarara, Uganda.
[Mulogo, Edgar] Mbarara Univ Sci & Technol, Dept Community Hlth, Mbarara, Uganda.
[Haberer, Jessica E.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA.
[Haberer, Jessica E.] Harvard Univ, Sch Med, Boston, MA USA.
RP Kiwanuka, J (reprint author), Mbarara Univ Sci & Technol, Dept Paediat & Child Hlth, Mbarara, Uganda.
EM jpkiwanuka@gmail.com
FU Canada-Africa Prevention Trials (CAPT) Network; US National Institutes
of Health [K23MH087228]
FX The study was funded by a mentorship grant from the Canada-Africa
Prevention Trials (CAPT) Network (captnetwork.org). Dr. Haberer was
supported by the US National Institutes of Health (K23MH087228). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 43
TC 8
Z9 8
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 25
PY 2014
VL 9
IS 3
AR e93276
DI 10.1371/journal.pone.0093276
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE0SD
UT WOS:000333675600161
PM 24667407
ER
PT J
AU Ferraro, A
D'Alise, AM
Raj, T
Asinovski, N
Phillips, R
Ergun, A
Replogle, JM
Bernier, A
Laffel, L
Stranger, BE
De Jager, PL
Mathis, D
Benoist, C
AF Ferraro, Alessandra
D'Alise, Anna Morena
Raj, Towfique
Asinovski, Natasha
Phillips, Roxanne
Ergun, Ayla
Replogle, Joseph M.
Bernier, Angelina
Laffel, Lori
Stranger, Barbara E.
De Jager, Philip L.
Mathis, Diane
Benoist, Christophe
TI Interindividual variation in human T regulatory cells
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE immunoregulation; suppression
ID TRANSCRIPTION FACTOR FOXP3; GENE-EXPRESSION; LINEAGE SPECIFICATION;
IMMUNE SUPPRESSION; FUNCTIONAL DEFECTS; REG CELLS; HOMEOSTASIS;
DIFFERENTIATION; INFLAMMATION; SIGNATURE
AB FOXP3(+) regulatory T (Treg) cells enforce immune self-tolerance and homeostasis, and variation in some aspects of Treg function may contribute to human autoimmune diseases. Here, we analyzed population-level Treg variability by performing genomewide expression profiling of CD4(+) Treg and conventional CD4(+) T (Tconv) cells from 168 donors, healthy or with established type-1 diabetes (T1D) or type-2 diabetes (T2D), in relation to genetic and immunologic screening. There was a range of variability in Treg signature transcripts, some almost invariant, others more variable, with more extensive variability for genes that control effector function (ENTPD1, FCRL1) than for lineage-specification factors like FOXP3 or IKZF2. Network analysis of Treg signature genes identified coregulated clusters that respond similarly to genetic and environmental variation in Treg and Tconv cells, denoting qualitative differences in otherwise shared regulatory circuits whereas other clusters are coregulated in Treg, but not Tconv, cells, suggesting Treg-specific regulation of genes like CTLA4 or DUSP4. Dense genotyping identified 110 local genetic variants (cis-expression quantitative trait loci), some of which are specifically active in Treg, but not Tconv, cells. The Treg signature became sharper with age and with increasing body-mass index, suggesting a tuning of Treg function with repertoire selection and/or chronic inflammation. Some Treg signature transcripts correlated with FOXP3 mRNA and/or protein, suggesting transcriptional or posttranslational regulatory relationships. Although no single transcript showed significant association to diabetes, overall expression of the Treg signature was subtly perturbed in T1D, but not T2D, patients.
C1 [Ferraro, Alessandra; D'Alise, Anna Morena; Asinovski, Natasha; Ergun, Ayla; Mathis, Diane; Benoist, Christophe] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA 02115 USA.
[Raj, Towfique; Replogle, Joseph M.; Stranger, Barbara E.; De Jager, Philip L.] Brigham & Womens Hosp, Program Translat NeuroPsychiat Genom, Dept Neurol, Boston, MA 02115 USA.
[Raj, Towfique; Replogle, Joseph M.; Stranger, Barbara E.; De Jager, Philip L.] Brigham & Womens Hosp, Div Genet, Dept Med, Boston, MA 02115 USA.
[Raj, Towfique; Replogle, Joseph M.; Stranger, Barbara E.; De Jager, Philip L.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Raj, Towfique; Replogle, Joseph M.; Stranger, Barbara E.; De Jager, Philip L.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA.
[Phillips, Roxanne; Bernier, Angelina; Laffel, Lori] Joslin Diabet Ctr, Dept Pediat Immunol, Boston, MA 02215 USA.
[Stranger, Barbara E.] Univ Chicago, Sect Genet Med, Dept Med, Chicago, IL 60637 USA.
RP Mathis, D (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA 02115 USA.
EM cbdm@hms.harvard.edu
OI Replogle, Joseph/0000-0003-1832-919X; Stranger,
Barbara/0000-0001-9021-7331
FU Juvenile Diabetes Research Foundation [4-2007-1057]; National Institutes
of Health [RC2 GM09308]
FX We thank Dr. D. Koller for helpful discussion; Katie Rothamel, Joyce
LaVecchio, and Girijesh Buruzula for help with flow cytometry and RNA
preparations; and Jeff Ericson, Scott Davis, and Henry Paik for help
with bioinformatics analyses. This work was supported by Juvenile
Diabetes Research Foundation Grant 4-2007-1057 (to D. M., C. B., and L.
L.) and National Institutes of Health Grant RC2 GM09308 (to D. M. and C.
B.).
NR 60
TC 26
Z9 26
U1 0
U2 9
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 25
PY 2014
VL 111
IS 12
BP E1111
EP E1120
DI 10.1073/pnas.1401343111
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6CK
UT WOS:000333341100009
PM 24610777
ER
PT J
AU Tao, JJ
Castel, P
Radosevic-Robin, N
Elkabets, M
Auricchio, N
Aceto, N
Weitsman, G
Barber, P
Vojnovic, B
Ellis, H
Morse, N
Viola-Villegas, NT
Bosch, A
Juric, D
Hazra, S
Singh, S
Kim, P
Bergamaschi, A
Maheswaran, S
Ng, T
Penault-Llorca, F
Lewis, JS
Carey, LA
Perou, CM
Baselga, J
Scaltriti, M
AF Tao, Jessica J.
Castel, Pau
Radosevic-Robin, Nina
Elkabets, Moshe
Auricchio, Neil
Aceto, Nicola
Weitsman, Gregory
Barber, Paul
Vojnovic, Borivoj
Ellis, Haley
Morse, Natasha
Viola-Villegas, Nerissa Therese
Bosch, Ana
Juric, Dejan
Hazra, Saswati
Singh, Sharat
Kim, Phillip
Bergamaschi, Anna
Maheswaran, Shyamala
Ng, Tony
Penault-Llorca, Frederique
Lewis, Jason S.
Carey, Lisa A.
Perou, Charles M.
Baselga, Jose
Scaltriti, Maurizio
TI Antagonism of EGFR and HER3 Enhances the Response to Inhibitors of the
PI3K-Akt Pathway in Triple-Negative Breast Cancer
SO SCIENCE SIGNALING
LA English
DT Article
ID CIRCULATING TUMOR-CELLS; INDUCTION CHEMOTHERAPY; TYROSINE KINASE;
THERAPY; COMBINATION; ACTIVATION; CARCINOMA; CETUXIMAB; ONCOLOGY;
SUPERIOR
AB Both abundant epidermal growth factor receptor (EGFR or ErbB1) and high activity of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway are common and therapeutically targeted in triple-negative breast cancer (TNBC). However, activation of another EGFR family member [human epidermal growth factor receptor 3 (HER3) (or ErbB3)] may limit the antitumor effects of these drugs. We found that TNBC cell lines cultured with the EGFR or HER3 ligand EGF or heregulin, respectively, and treated with either an Akt inhibitor (GDC0068) or a PI3K inhibitor (GDC-0941) had increased abundance and phosphorylation of HER3. The phosphorylation of HER3 and EGFR in response to these treatments was reduced by the addition of a dual EGFR and HER3 inhibitor (MEHD7945A). MEHD7945A also decreased the phosphorylation (and activation) of EGFR and HER3 and the phosphorylation of downstream targets that occurred in response to the combination of EGFR ligands and PI3K-Akt pathway inhibitors. In culture, inhibition of the PI3K-Akt pathway combined with either MEHD7945A or knockdown of HER3 decreased cell proliferation compared with inhibition of the PI3K-Akt pathway alone. Combining either GDC-0068 or GDC-0941 with MEHD7945A inhibited the growth of xenografts derived from TNBC cell lines or from TNBC patient tumors, and this combination treatment was also more effective than combining either GDC-0068 or GDC-0941 with cetuximab, an EGFR-targeted antibody. After therapy with EGFR-targeted antibodies, some patients had residual tumors with increased HER3 abundance and EGFR/HER3 dimerization (an activating interaction). Thus, we propose that concomitant blockade of EGFR, HER3, and the PI3K-Akt pathway in TNBC should be investigated in the clinical setting.
C1 [Tao, Jessica J.; Auricchio, Neil; Aceto, Nicola; Juric, Dejan; Maheswaran, Shyamala] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
[Tao, Jessica J.; Auricchio, Neil; Aceto, Nicola; Juric, Dejan; Maheswaran, Shyamala] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Castel, Pau; Elkabets, Moshe; Ellis, Haley; Morse, Natasha; Bosch, Ana; Baselga, Jose; Scaltriti, Maurizio] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
[Radosevic-Robin, Nina; Penault-Llorca, Frederique] Ctr Jean Perrin, Dept Biopathol, F-63011 Clermont Ferrand, France.
[Radosevic-Robin, Nina; Penault-Llorca, Frederique] Univ Auvergne, ERTICA EA4677, F-63000 Clermont Ferrand, France.
[Weitsman, Gregory; Ng, Tony] Kings Coll London, Randall Div Cell & Mol Biophys, Richard Dimbleby Dept Canc Res, London SE1 1UL, England.
[Weitsman, Gregory; Ng, Tony] Kings Coll London, Div Canc Studies, London SE1 1UL, England.
[Barber, Paul; Vojnovic, Borivoj] Univ Oxford, Dept Oncol, Gray Inst Radiat Oncol & Biol, Oxford OX3 7DQ, England.
[Barber, Paul] Kings Coll London, Inst Math & Mol Biomed, London SE1 1UL, England.
[Vojnovic, Borivoj] Kings Coll London, Randall Div Cell & Mol Biophys, London SE1 1UL, England.
[Viola-Villegas, Nerissa Therese; Lewis, Jason S.] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10065 USA.
[Viola-Villegas, Nerissa Therese; Lewis, Jason S.] Mem Sloan Kettering Canc Ctr, Program Mol Pharmacol & Chem, New York, NY 10065 USA.
[Hazra, Saswati; Singh, Sharat; Kim, Phillip] Prometheus Therapeut & Diagnost, San Diego, CA 92121 USA.
[Bergamaschi, Anna] Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA.
[Ng, Tony] UCL, UCL Canc Inst, London WC1E 6DD, England.
[Carey, Lisa A.] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA.
[Perou, Charles M.] Univ N Carolina, Dept Genet, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
RP Baselga, J (reprint author), Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, 1275 York Ave,Box 20, New York, NY 10065 USA.
EM baselgaj@mskcc.org; scaltrim@mskcc.org
RI Aceto, Nicola/O-2484-2014;
OI Vojnovic, Borivoj/0000-0001-9013-3816; Aceto,
Nicola/0000-0001-9579-6918; Castel, Pau/0000-0002-4972-4347; Perou,
Charles/0000-0001-9827-2247
FU Amgen and the Jean Perrin Comprehensive Cancer Center; Susan G. Komen
for the Cure [SAC110046]; Breast Cancer Research Foundation; CRUK;
Engineering and Physical Sciences Research Council in association with
the Medical Research Council and Department of Health (England)
[C1519/A10331]; European Union grant [259881]; Spanish Society of
Medical Oncology (SEOM); National Cancer Institute Breast SPORE
(Specialized Program of Research Excellence) program [P50-CA58223-09A1];
Swiss Foundation; Swiss National Science Foundation
FX The clinical panitumumab study conducted in France was sponsored by
Amgen and the Jean Perrin Comprehensive Cancer Center. Preclinical work
was funded by Susan G. Komen for the Cure (SAC110046) and the Breast
Cancer Research Foundation. King's College London-University College
London Comprehensive Cancer Imaging Centre funding was provided by CRUK
and the Engineering and Physical Sciences Research Council in
association with the Medical Research Council and Department of Health
(England; C1519/A10331) and an FP7-HEALTH-2010 European Union grant
entitled "IMAGINT" (grant number 259881). M.E. is an International
Sephardic Education Foundation postdoctoral fellow; A.B. holds a
Translational Research Fellowship from the Spanish Society of Medical
Oncology (SEOM); C.M.P. is funded by the National Cancer Institute
Breast SPORE (Specialized Program of Research Excellence) program
(P50-CA58223-09A1) and the Breast Cancer Research Foundation; and N.
Aceto is a fellow of the Human Frontiers Science Program, the Swiss
National Science Foundation, and the Swiss Foundation for Grants in
Biology and Medicine.
NR 43
TC 40
Z9 41
U1 2
U2 12
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1945-0877
EI 1937-9145
J9 SCI SIGNAL
JI Sci. Signal.
PD MAR 25
PY 2014
VL 7
IS 318
AR ra29
DI 10.1126/scisignal.2005125
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AD9BD
UT WOS:000333558600004
PM 24667376
ER
PT J
AU Corcoran, C
Rani, S
Breslin, S
Gogarty, M
Ghobrial, IM
Crown, J
O'Driscoll, L
AF Corcoran, Claire
Rani, Sweta
Breslin, Susan
Gogarty, Martina
Ghobrial, Irene M.
Crown, John
O'Driscoll, Lorraine
TI miR-630 targets IGF1R to regulate response to HER-targeting drugs and
overall cancer cell progression in HER2 over-expressing breast cancer
SO MOLECULAR CANCER
LA English
DT Article
DE MicroRNA-630; IGF1R; Biomarker; Breast cancer; Drug resistance; Cancer
cell aggression
ID FACTOR-I RECEPTOR; TYROSINE KINASE INHIBITOR; GROWTH-FACTOR RECEPTOR;
TUMOR-CELLS; EXTRACELLULAR MICRORNAS; TRASTUZUMAB RESISTANCE; LAPATINIB;
LINES; ACTIVATION; INVASION
AB Background: While the treatment of HER2 over-expressing breast cancer with recent HER-targeted drugs has been highly effective for some patients, primary (also known as innate) or acquired resistance limits the success of these drugs. microRNAs have potential as diagnostic, prognostic and predictive biomarkers, as well as replacement therapies. Here we investigated the role of microRNA-630 (miR-630) in breast cancer progression and as a predictive biomarker for response to HER-targeting drugs, ultimately yielding potential as a therapeutic approach to add value to these drugs.
Methods: We investigated the levels of intra-and extracellular miR-630 in cells and conditioned media from breast cancer cell lines with either innate-or acquired-resistance to HER-targeting lapatinib and neratinib, compared to their corresponding drug sensitive cell lines, using qPCR. To support the role of miR-630 in breast cancer, we examined the clinical relevance of this miRNA in breast cancer tumours versus matched peritumours. Transfection of miR-630 mimics and inhibitors was used to manipulate the expression of miR-630 to assess effects on response to HER-targeting drugs (lapatinib, neratinib and afatinib). Other phenotypic changes associated with cellular aggressiveness were evaluated by motility, invasion and anoikis assays. TargetScan prediction software, qPCR, immunoblotting and ELISAs, were used to assess miR-630's regulation of mRNA, proteins and their phosphorylated forms.
Results: We established that introducing miR-630 into cells with innate-or acquired-resistance to HER-drugs significantly restored the efficacy of lapatinib, neratinib and afatinib; through a mechanism which we have determined to, at least partly, involve miR-630's regulation of IGF1R. Conversely, we demonstrated that blocking miR-630 induced resistance/insensitivity to these drugs. Cellular motility, invasion, and anoikis were also observed as significantly altered by miR-630 manipulation, whereby introducing miR-630 into cells reduced cellular aggression while inhibition of miR-630 induced a more aggressive cellular phenotype.
Conclusions: Taken together, our findings suggest miR-630 as a key regulator of cancer cell progression in HER2 over-expressing breast cancer, through targeting of IGF1R. This study supports miR-630 as a diagnostic and a predictive biomarker for response to HER-targeted drugs and indicates that the therapeutic addition of miR-630 may enhance and improve patients' response to HER-targeting drugs.
C1 [Corcoran, Claire; Rani, Sweta; Breslin, Susan; Gogarty, Martina; O'Driscoll, Lorraine] Univ Dublin Trinity Coll, Sch Pharm & Pharmaceut Sci, Dublin 2, Ireland.
[Corcoran, Claire; Rani, Sweta; Breslin, Susan; Gogarty, Martina; O'Driscoll, Lorraine] Univ Dublin Trinity Coll, Trinity Biomed Sci Inst, Dublin 2, Ireland.
[Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Crown, John] St Vincents Univ Hosp, Dept Oncol, Dublin 4, Ireland.
RP O'Driscoll, L (reprint author), Univ Dublin Trinity Coll, Sch Pharm & Pharmaceut Sci, Dublin 2, Ireland.
EM lodrisc@tcd.ie
OI O'Driscoll, Lorraine/0000-0002-9860-8262
FU Science Foundation Ireland's funding of MTCI [08/SRC/B1410]; SFGamma's
Short Term Travel Fellowship [STTGamma-11]; Marie Keating Foundation;
TBSI; Irish Cancer Society; Breast-PREDICT [CCRC13GAL]; Health Research
Board [HRA_ POR/2013/342]; EU COST Action ME-HaD [BM1202]
FX This work was supported by Science Foundation Ireland's funding of MTCI
[08/SRC/B1410]; SF Gamma's Short Term Travel Fellowship [ST Gamma-11];
Marie Keating Foundation; the Higher Education Authority's PRTLI Cycle 5
support of TBSI; Irish Cancer Society's support of Breast-PREDICT
[CCRC13GAL]; and the Health Research Board [HRA_ POR/2013/342]; and EU
COST Action ME-HaD (BM1202).
NR 43
TC 29
Z9 31
U1 1
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-4598
J9 MOL CANCER
JI Mol. Cancer
PD MAR 24
PY 2014
VL 13
AR 71
DI 10.1186/1476-4598-13-71
PG 12
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA AF2NY
UT WOS:000334550000001
PM 24655723
ER
PT J
AU Hajjarian, Z
Nadkarni, SK
AF Hajjarian, Zeinab
Nadkarni, Seemantini K.
TI Correction of optical absorption and scattering variations in laser
speckle rheology measurements
SO OPTICS EXPRESS
LA English
DT Article
ID DIFFUSING-WAVE-SPECTROSCOPY; SPATIAL-FREQUENCY DOMAIN; DYNAMIC
LIGHT-SCATTERING; COMPLEX FLUIDS; VISCOELASTIC MODULI; TISSUE; MIXTURES;
EQUATION; LIMIT; MILK
AB Laser Speckle Rheology (LSR) is an optical technique to evaluate the viscoelastic properties by analyzing the temporal fluctuations of backscattered speckle patterns. Variations of optical absorption and reduced scattering coefficients further modulate speckle fluctuations, posing a critical challenge for quantitative evaluation of viscoelasticity. We compare and contrast two different approaches applicable for correcting and isolating the collective influence of absorption and scattering, to accurately measure mechanical properties. Our results indicate that the numerical approach of Monte-Carlo ray tracing (MCRT) reliably compensates for any arbitrary optical variations. When scattering dominates absorption, yet absorption is non-negligible, diffusing wave spectroscopy (DWS) formalisms perform similar to MCRT, superseding other analytical compensation approaches such as Telegrapher equation. The computational convenience of DWS greatly simplifies the extraction of viscoelastic properties from LSR measurements in a number of chemical, industrial, and biomedical applications. (C) 2014 Optical Society of America
C1 [Hajjarian, Zeinab; Nadkarni, Seemantini K.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Nadkarni, SK (reprint author), Harvard Univ, Sch Med, Wellman Ctr Photomed, Massachusetts Gen Hosp, 40 Blossom St, Boston, MA 02114 USA.
EM snadkarni@partners.org
FU NIH [R21 HL 088306, U54 EB015408-01]; ARRA [R21 HL 088306-02S1]
FX This study was funded by the NIH grant No. R21 HL 088306 (S.N), NIH
grant No. U54 EB015408-01 (S.N), and the ARRA grant No. R21 HL
088306-02S1 (S.N).
NR 37
TC 5
Z9 5
U1 2
U2 14
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 1094-4087
J9 OPT EXPRESS
JI Opt. Express
PD MAR 24
PY 2014
VL 22
IS 6
BP 6349
EP 6361
DI 10.1364/OE.22.006349
PG 13
WC Optics
SC Optics
GA AD9IT
UT WOS:000333579300016
PM 24663983
ER
PT J
AU Baac, HW
Uribe-Patarroyo, N
Bouma, BE
AF Baac, Hyoung Won
Uribe-Patarroyo, Nestor
Bouma, Brett E.
TI High-energy pulsed Raman fiber laser for biological tissue coagulation
SO OPTICS EXPRESS
LA English
DT Article
ID MU-M; POWER; IMPACT; NM
AB We demonstrate a high-energy pulsed Raman fiber laser (RFL) with an emission wavelength of 1.44 mu m, corresponding to an absorption peak of water. Microsecond pulses with > 20 mJ/pulse and > 40 W peak power were generated, well above the threshold for tissue coagulation and ablation. Here, we focus on the optical characterization and optimization of high-energy and high-power RFLs excited by an ytterbium fiber laser, comparing three configurations that use different Raman gain fibers, but all of which were prepared with a one-side opened, free-run mode without output mirrors. We show that the free-run configuration can generate sufficiently high energy without requiring a closed cavity design. Experimental RFL characteristics corresponded well with numerical simulations. We discuss the Stokes beam generation process in our system and loss mechanisms mainly associated with fiber Bragg gratings. (C)2014 Optical Society of America
C1 [Baac, Hyoung Won] Harvard Univ, Sch Med, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
RP Baac, HW (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA.
EM baac.hyoungwon@mgh.harvard.edu
FU National Institutes of Health [P41 EB015903]; NinePoint Medical
FX Research reported in this publication was supported in part by the
National Institutes of Health, grant P41 EB015903 and NinePoint Medical.
The authors thank nLight Photonics for providing access to and technical
support for the ytterbium fiber laser used in this work.
NR 24
TC 7
Z9 7
U1 2
U2 9
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 1094-4087
J9 OPT EXPRESS
JI Opt. Express
PD MAR 24
PY 2014
VL 22
IS 6
BP 7113
EP 7123
DI 10.1364/OE.22.007113
PG 11
WC Optics
SC Optics
GA AD9IT
UT WOS:000333579300090
PM 24664059
ER
PT J
AU Dimant, H
Zhu, LY
Kibuuka, LN
Fan, Z
Hyman, BT
McLean, PJ
AF Dimant, Hemi
Zhu, Liya
Kibuuka, Laura N.
Fan, Zhanyun
Hyman, Bradley T.
McLean, Pamela J.
TI Direct Visualization of CHIP-Mediated Degradation of Alpha-Synuclein In
Vivo: Implications for PD Therapeutics
SO PLOS ONE
LA English
DT Article
ID PARKINSONS-DISEASE; LEWY BODIES; C-TERMINUS; AGGREGATION; OLIGOMERS;
TOXICITY; APOPTOSIS; PROTEINS; TARGETS
AB Parkinson's disease is a neurodegenerative disorder characterized by Lewy bodies, a pathological hallmark comprised mostly of aggregated alpha synuclein. Accumulating evidence demonstrates the association of smaller oligomeric aggregates to disease etiology and many therapeutic approaches are aimed at inhibiting and reducing the aggregation process. Molecular chaperones and co-chaperones play a key role in protein homeostasis and have potential as therapeutics to inhibit alpha synuclein associated toxicity. Here we use a gene therapy approach to evaluate the applicability of the Hsp70 co-chaperone CHIP (C-terminal Hsp70 interacting protein) as a therapeutic candidate and examine its direct effect on alpha synuclein aggregates in vivo. Utilizing a novel viral vector mediated rat model to directly detect alpha synuclein aggregates, we show that CHIP can mediate the degradation of alpha synuclein aggregates in vivo. However, our studies also reveal that CHIP may potentially degrade tyrosine hydroxylase which would compromise the applicability of CHIP as a therapeutic approach for Parkinson's disease.
C1 [Dimant, Hemi; Zhu, Liya; Kibuuka, Laura N.; Fan, Zhanyun; Hyman, Bradley T.; McLean, Pamela J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGeneral Inst Neurodegenerat Dis,Dept Neurol, Charlestown, MA 02129 USA.
[McLean, Pamela J.] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA.
RP McLean, PJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGeneral Inst Neurodegenerat Dis,Dept Neurol, Charlestown, MA 02129 USA.
EM mclean.pamela@mayo.edu
FU NIH [NS063963]; Ruth L. Kirschstein National Research Service Award
(NRSA) Institutional Research Training Grants (T32)
FX PM is supported by NIH NS063963. HD is supported by Ruth L. Kirschstein
National Research Service Award (NRSA) Institutional Research Training
Grants (T32). The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 19
TC 2
Z9 2
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 24
PY 2014
VL 9
IS 3
AR e92098
DI 10.1371/journal.pone.0092098
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD7QO
UT WOS:000333459900040
PM 24664141
ER
PT J
AU Mukherjee, A
Larson, EA
Klein, RF
Rotwein, P
AF Mukherjee, Aditi
Larson, Emily A.
Klein, Robert F.
Rotwein, Peter
TI Distinct Actions of Akt1 on Skeletal Architecture and Function
SO PLOS ONE
LA English
DT Article
ID MICE LACKING; OSTEOBLAST DIFFERENTIATION; CELL-SURVIVAL;
PHOSPHATIDYLINOSITOL 3-KINASE; GLUCOSE-HOMEOSTASIS; BONE; GROWTH;
KINASE; OSTEOPOROSIS; OSTEOCLAST
AB Skeletal integrity is dependent on the coordinated actions of bone-forming osteoblasts and bone-resorbing osteoclasts, which recognize and respond to multiple environmental inputs. Here we have studied the roles in bone development and growth of Akt1 and Akt2, two closely related signaling proteins, by evaluating mice lacking either of these enzymes. Global deficiency of Akt1 but not Akt2 caused a reduction in whole body and femoral bone mineral density, in femoral cortical thickness and volume, and in trabecular thickness in both males and females when measured at 20-weeks of age, which was reflected in diminished femoral resistance to fracture. Haplo-deficiency of Akt1 in male mice also decreased femoral cortical and trabecular skeletal parameters, and reduced bone strength. Cell-based studies showed that genetic Akt1 deficiency diminished the rate of proliferation of osteoblast progenitors and impaired osteoclast differentiation in primary culture but that loss of Akt2 did not. Our results demonstrate differential effects of Akt1 and Akt2 on skeletal maturation and architecture through actions on both osteoblast and osteoclast precursors.
C1 [Mukherjee, Aditi; Rotwein, Peter] Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97201 USA.
[Larson, Emily A.; Klein, Robert F.] Oregon Hlth & Sci Univ, Dept Med, Bone & Mineral Res Unit, Portland, OR 97201 USA.
[Klein, Robert F.] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA.
RP Rotwein, P (reprint author), Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97201 USA.
EM rotweinp@ohsu.edu
FU NIH [R01 DK42748]; VA Medical Research Service; OHSU Medical Research
Foundation
FX These studies were supported in part by NIH grant R01 DK42748 (to P.
R.), by the VA Medical Research Service (R. F. K.), and by an OHSU
Medical Research Foundation new investigator grant (to A. M.). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 50
TC 2
Z9 2
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 24
PY 2014
VL 9
IS 3
AR e93040
DI 10.1371/journal.pone.0093040
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD7QO
UT WOS:000333459900147
PM 24663486
ER
PT J
AU Kahn, SE
Cooper, ME
Del Prato, S
AF Kahn, Steven E.
Cooper, Mark E.
Del Prato, Stefano
TI Pathophysiology and treatment of type 2 diabetes: perspectives on the
past, present, and future
SO LANCET
LA English
DT Review
ID BETA-CELL FUNCTION; GLUCAGON-LIKE PEPTIDE-1; IMPAIRED GLUCOSE-TOLERANCE;
LIFE-STYLE INTERVENTION; TODAY CLINICAL-TRIAL; 11-BETA-HYDROXYSTEROID
DEHYDROGENASE TYPE-1; DIPEPTIDYL PEPTIDASE-4 INHIBITORS; PREVENTION
PROGRAM OUTCOMES; FIBROBLAST GROWTH-FACTORS; INSULIN-TREATED PATIENTS
AB Glucose metabolism is normally regulated by a feedback loop including islet beta cells and insulin-sensitive tissues, in which tissue sensitivity to insulin affects magnitude of beta-cell response. If insulin resistance is present, beta cells maintain normal glucose tolerance by increasing insulin output. Only when beta cells cannot release sufficient insulin in the presence of insulin resistance do glucose concentrations rise. Although beta-cell dysfunction has a clear genetic component, environmental changes play an essential part. Modern research approaches have helped to establish the important role that hexoses, aminoacids, and fatty acids have in insulin resistance and beta-cell dysfunction, and the potential role of changes in the microbiome. Several new approaches for treatment have been developed, but more effective therapies to slow progressive loss of beta-cell function are needed. Recent findings from clinical trials provide important information about methods to prevent and treat type 2 diabetes and some of the adverse effects of these interventions. However, additional long-term studies of drugs and bariatric surgery are needed to identify new ways to prevent and treat type 2 diabetes and thereby reduce the harmful effects of this disease.
C1 [Kahn, Steven E.] Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA.
[Cooper, Mark E.] Baker IDI Heart & Diabet Inst, Diabet Div, Melbourne, Vic, Australia.
[Del Prato, Stefano] Univ Pisa, Sch Med, Dept Clin & Expt Med, I-56100 Pisa, Italy.
RP Kahn, SE (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA.
EM skahn@uw.edu
RI Del Prato, Stefano/K-3405-2016;
OI Del Prato, Stefano/0000-0002-5388-0270; Kahn, Steven/0000-0001-7307-9002
FU US Department of Veterans Affairs; NIH [DK-017047]; National Health and
Medical Research Council of Australia; Italian Ministry of Education and
Research [2010YK7Z5K_006]
FX SEK is supported partly by the US Department of Veterans Affairs and NIH
grant DK-017047. MEC is supported by an Australia Fellowship from the
National Health and Medical Research Council of Australia. SDP was
supported by grant 2010YK7Z5K_006 from the Italian Ministry of Education
and Research.
NR 202
TC 203
Z9 213
U1 24
U2 151
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD MAR 22
PY 2014
VL 383
IS 9922
BP 1068
EP 1083
DI 10.1016/S0140-6736(13)62154-6
PG 16
WC Medicine, General & Internal
SC General & Internal Medicine
GA AD8MV
UT WOS:000333521200033
PM 24315620
ER
PT J
AU He, LZ
Marneros, AG
AF He, Lizhi
Marneros, Alexander G.
TI Doxycycline Inhibits Polarization of Macrophages to the Proangiogenic
M2-type and Subsequent Neovascularization
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Angiogenesis; Antibiotics; Inflammation; Innate Immunity; Macrophages;
Wound Healing; Macular Degeneration
ID CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION; MEDIATED INHIBITION;
ANGIOGENESIS; PREVENTS; RANIBIZUMAB; BEVACIZUMAB; PROGRESSION; MECHANISM
AB Background: M2-type macrophages are proangiogenic and protumorigenic, whereas M1-type macrophages are antiangiogenic. Results: Doxycycline is a potent inhibitor of M2-type macrophage polarization in both human and mouse macrophages in vitro and in vivo. Conclusion: Preventing M2-type macrophage polarization correlates with inhibition of pathological angiogenesis. Significance: Doxycycline may be used to enhance current antiangiogenic treatment approaches in neovascular age-related macular degeneration and in certain cancers.
Macrophages occur along a continuum of functional states between M1-type polarized macrophages with antiangiogenic and antitumor activity and M2-type polarized macrophages, which have been implicated to promote angiogenesis and tumor growth. Proangiogenic M2-type macrophages promote various pathologic conditions, including choroidal neovascularization in models of neovascular age-related macular degeneration, or certain cancers, such as glioblastoma multiforme. Thus, a potential novel therapeutic approach to target pathological angiogenesis in these conditions would be to inhibit the polarization of macrophages toward the proangiogenic M2-type. However, no pharmacological inhibitors of M2-type macrophage polarization have been identified yet. Here we performed an unbiased pharmacological and small chemical screen to identify drugs that inhibit proangiogenic M2-type macrophage polarization and block pathologic macrophage-driven neovascularization. We identified the well tolerated and commonly used antibiotic doxycycline as a potent inhibitor of M2-type polarization of macrophages. Doxycycline inhibited, in a dose-dependent manner, M2-type polarization of human and bone marrow-derived mouse macrophages without affecting cell viability. Furthermore, doxycycline inhibited M2-type macrophage polarization and subsequent neovascularization in vivo in a laser injury model of choroidal neovascularization. Thus, doxycycline could be used to enhance current antiangiogenic treatment approaches in various conditions that are promoted by proangiogenic M2-type macrophages, including neovascular age-related macular degeneration and certain cancers.
C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA.
Harvard Univ, Sch Med, Dept Dermatol, Charlestown, MA 02129 USA.
RP Marneros, AG (reprint author), CBRC, MGH East, CNY-149,Rm 3-216,13th St, Charlestown, MA 02129 USA.
EM amarneros@mgh.harvard.edu
FU NEI, National Institutes of Health [NEI R01-EY019297]; Shiseido research
grant; Dermatology Foundation
FX This study was supported, in whole or in part, by NEI, National
Institutes of Health Grant NEI R01-EY019297 (to A. G. M.). This work was
also supported by a Shiseido research grant (to A. G. M.) and by a
Dermatology Foundation research grant (to L. H.).
NR 18
TC 13
Z9 16
U1 2
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 21
PY 2014
VL 289
IS 12
BP 8019
EP 8028
DI 10.1074/jbc.M113.535765
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AD3PG
UT WOS:000333157500002
PM 24505138
ER
PT J
AU Ghatak, S
Misra, S
Norris, RA
Moreno-Rodriguez, RA
Hoffman, S
Levine, RA
Hascall, VC
Markwald, RR
AF Ghatak, Shibnath
Misra, Suniti
Norris, Russell A.
Moreno-Rodriguez, Ricardo A.
Hoffman, Stanley
Levine, Robert A.
Hascall, Vincent C.
Markwald, Roger R.
TI Periostin Induces Intracellular Cross-talk between Kinases and
Hyaluronan in Atrioventricular Valvulogenesis
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Cd44; Cell Adhesion; Cell Migration; Collagen; Hyaluronate; Integrins;
Atrioventricular Valve; Intracellular Kinase Signaling; Periostin;
Prevalvular Cushion Cells
ID FOCAL ADHESION KINASE; CONSTITUTIVELY REGULATES ACTIVATION; CARDIAC
VALVULAR DYSTROPHY; HUMAN MESANGIAL CELLS; CANCER-CELLS;
CARCINOMA-CELLS; PROTEIN-KINASE; FILAMIN-A; VALVE DEVELOPMENT;
GROWTH-FACTOR
AB Background: Periostin-null mice exhibit a myxomatous atrioventricular valve phenotype. We propose two mechanisms as follows: periostin binds to collagen and links it to cell-surface receptors; periostin/-INTEGRIN signaling promotes valve morphogenesis. Results: Periostin/-INTEGRINs/focal adhesion kinase/PI3K/ERK signals promote hyaluronan synthase-2 activation, matrix remodeling, and valve progenitor cell survival/differentiation. Conclusion: The phenotype of periostin-null valves is consistent with a role for PN cell signaling through INTEGRIN receptors. Significance: Periostin is a valvulogenic signaling morphogen.
Periostin (PN), a novel fasciclin-related matricellular protein, has been implicated in cardiac development and postnatal remodeling, but the mechanism remains unknown. We examined the role of PN in mediating intracellular kinase activation for atrioventricular valve morphogenesis using well defined explant cultures, gene transfection systems, and Western blotting. The results show that valve progenitor (cushion) cells secrete PN into the extracellular matrix, where it can bind to INTEGRINs and activate INTEGRIN/focal adhesion kinase signaling pathways and downstream kinases, PI3K/AKT and ERK. Functional assays with prevalvular progenitor cells showed that activating these signaling pathways promoted adhesion, migration, and anti-apoptosis. Through activation of PI3K/ERK, PN directly enhanced collagen expression. Comparing PN-null to WT mice also revealed that expression of hyaluronan (HA) and activation of hyaluronan synthase-2 (Has2) are also enhanced upon PN/INTEGRIN/focal adhesion kinase-mediated activation of PI3K and/or ERK, an effect confirmed by the reduction of HA synthase-2 in PN-null mice. We also identified in valve progenitor cells a potential autocrine signaling feedback loop between PN and HA through PI3K and/or ERK. Finally, in a three-dimensional assay to simulate normal valve maturation in vitro, PN promoted collagen compaction in a kinase-dependent fashion. In summary, this study provides the first direct evidence that PN can act to stimulate a valvulogenic signaling pathway.
C1 [Ghatak, Shibnath; Misra, Suniti; Norris, Russell A.; Moreno-Rodriguez, Ricardo A.; Markwald, Roger R.] Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA.
[Hoffman, Stanley] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA.
[Levine, Robert A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Hascall, Vincent C.] Cleveland Clin, Dept Biomed Engn ND20, Cleveland, OH 44195 USA.
RP Markwald, RR (reprint author), Med Univ S Carolina, Dept Regenerat Med & Cell Biol, 173 Ashley Ave, Charleston, SC 29425 USA.
EM markwald@musc.edu
FU National Institutes of Health [1R03CA167722-01A1, P20RR021949,
P20RR016434, P20RR16461-05, RO1-HL033756-24, P01HL107147, 1P30AR050953];
EPS [0903795]; MCRC [39919]; COBRE [IP30-GM103342, 8P20 GM103444];
Fondation Leducq (Paris, France) Transatlantic Network of Excellence
[07CDV04]; American Heart Association [11SDG5270006]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants 1R03CA167722-01A1 (to S. M. and S. G.), P20RR021949 (to S.
G.), P20RR016434 (to S. M., S. G., and R. R. M.), P20RR16461-05 (to S.
G. and R. R. M), RO1-HL033756-24 and (to S. M., S. G., and R. R. M.),
P01HL107147 and 1P30AR050953 (to V. C. H.), EPS 0903795 (to S. M.), MCRC
39919 (to S. G. and S. M.), COBRE IP30-GM103342 (to R. R. M. and R. A.
N.), and 8P20 GM103444 (to R. R. M. and R. A. N.). This work was also
supported by Fondation Leducq (Paris, France) Transatlantic Network of
Excellence Grant 07CDV04 (to R. A. L.) and American Heart Association
Grant 11SDG5270006 (to R. A. N.).
NR 72
TC 11
Z9 11
U1 2
U2 11
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 21
PY 2014
VL 289
IS 12
BP 8545
EP 8561
DI 10.1074/jbc.M113.539882
PG 17
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AD3PG
UT WOS:000333157500045
PM 24469446
ER
PT J
AU Vecchio, D
Bhayana, B
Huang, LY
Carrasco, E
Evans, CL
Hamblin, MR
AF Vecchio, Daniela
Bhayana, Brijesh
Huang, Liyi
Carrasco, Elisa
Evans, Conor L.
Hamblin, Michael R.
TI Structure-function relationships of Nile blue (EtNBS) derivatives as
antimicrobial photosensitizers
SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
DE Structure-activity relationships; Benzophenothiazinium dye; Nile blue
derivatives, antimicrobial; photodynamic inactivation; Gram-positive
bacteria; Gram-negative bacteria; Electron withdrawing/donating
substituents
ID PHOTODYNAMIC THERAPY; CLINICAL-APPLICATIONS; IN-VITRO;
BENZOPHENOTHIAZINE; PHOTOTOXICITY; RESISTANCE; BACTERIA; EFFICACY;
ANALOGS; MODELS
AB The benzophenothiazinium dye EtNBS has previously been tested as a photosensitizer to mediate photodynamic therapy (PDT). It has been employed to kill cancer cells and microbial cells in vitro and to treat tumors and infections in vivo. We synthesized a panel of derivatives substituted at the 1-position of the benzene ring with electron donating or electron withdrawing groups (amino, acetamido and nitro) and tested their production of reactive oxygen species (ROS) and light-mediated killing of two species of Gram-positive and two species of Gram-negative bacteria. All three compounds showed lower fluorescence, lower yield of ROS and less microbial killing than parent EtNBS, while the order of activity (nitro > amino > acetamido) showed that an electron withdrawing substituent was better than electron donating. To test the hypothesis that 1-substitution distorts the planar structure of the conjugated rings we compared two compounds substituted with N-ethylpropylsulfonamido either at the 1-position or at the 4-position. The 4-isomer was significantly more photoactive than the 1-isomer. We also prepared an EtNBS derivative with a guanidinium group attached to the 5-amino group. This compound had high activity against Gram-negative bacteria due to the extra positive charge. Cellular uptake of the compounds by the four bacterial species was also measured and broadly correlated with activity. These results provided three separate pieces of structure activity relationship data for antimicrobial photosensitizers based on the EtNBS backbone. (C) 2014 Elsevier Masson SAS. All rights reserved.
C1 [Vecchio, Daniela; Bhayana, Brijesh; Huang, Liyi; Carrasco, Elisa; Evans, Conor L.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Vecchio, Daniela; Huang, Liyi; Evans, Conor L.; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
[Huang, Liyi] Guangxi Med Univ, Affiliated Coll & Hosp 1, Dept Infect Dis, Nanning 530021, Peoples R China.
[Carrasco, Elisa] Univ Autonoma Madrid, Fac Ciencias, Dept Biol, E-28049 Madrid, Spain.
[Carrasco, Elisa] Univ Autonoma Madrid, Fac Med, CSIC, Inst Invest Biomed Alberto Sols,Dept Bioquim, E-28029 Madrid, Spain.
[Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
RP Hamblin, MR (reprint author), BAR414,40 Blossom St, Boston, MA 02114 USA.
EM Hamblin@helix.mgh.harvard.edu
RI Carrasco, Elisa/G-7746-2015;
OI Carrasco, Elisa/0000-0002-0817-1627; Hamblin,
Michael/0000-0001-6431-4605
FU US NIH [R01AI050875, DP2OD007096]
FX This work was supported by US NIH grant R01AI050875 to MRH and US NIH
Director's New Innovator Award, grant number DP2OD007096 to CLE.
Information on the New Innovator Award Program is at
http://nihroadmap.nih.gov/newinnovator/. The funding sources had no
involvement in the study design; in the collection, analysis and
interpretation of data; in the writing of the report; or in the decision
to submit the article for publication.
NR 29
TC 8
Z9 8
U1 0
U2 13
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI PARIS
PA 23 RUE LINOIS, 75724 PARIS, FRANCE
SN 0223-5234
EI 1768-3254
J9 EUR J MED CHEM
JI Eur. J. Med. Chem.
PD MAR 21
PY 2014
VL 75
BP 479
EP 491
DI 10.1016/j.ejmech.2014.01.064
PG 13
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA AE2AL
UT WOS:000333775600046
PM 24561676
ER
PT J
AU Hsieh, LC
Chen, JW
Wang, LY
Tsang, YM
Shueng, PW
Liao, LJ
Lo, WC
Lin, YC
Tseng, CF
Kuo, YS
Jhuang, JY
Tien, HJ
Juan, HF
Hsieh, CH
AF Hsieh, Li-Chun
Chen, John W.
Wang, Li-Ying
Tsang, Yuk-Ming
Shueng, Pei-Wei
Liao, Li-Jen
Lo, Wu-Chia
Lin, Yu-Chin
Tseng, Chien-Fu
Kuo, Ying-Shiung
Jhuang, Jie-Yang
Tien, Hui-Ju
Juan, Hsueh-Fen
Hsieh, Chen-Hsi
TI Predicting the Severity and Prognosis of Trismus after
Intensity-Modulated Radiation Therapy for Oral Cancer Patients by
Magnetic Resonance Imaging
SO PLOS ONE
LA English
DT Article
ID NASOPHARYNGEAL CARCINOMA; POSTOPERATIVE TREATMENT; NECK RADIOTHERAPY;
CAVITY CANCER; HEAD; EXPERIENCE; SEQUELAE; TERMS
AB To develop magnetic resonance imaging (MRI) indicators to predict trismus outcome for post-operative oral cavity cancer patients who received adjuvant intensity-modulated radiation therapy (IMRT), 22 patients with oral cancer treated with IMRT were studied over a two-year period. Signal abnormality scores (SA scores) were computed from Likert-type ratings of the abnormalities of nine masticator structures and compared with the Mann-Whitney U-test and Kruskal-Wallis one-way ANOVA test between groups. Seventeen patients (77.3%) experienced different degrees of trismus during the two-year follow-up period. The SA score correlated with the trismus grade (r = 0.52, p < 0.005). Patients having progressive trismus had higher mean doses of radiation to multiple structures, including the masticator and lateral pterygoid muscles, and the parotid gland (p < 0.05). In addition, this group also had higher SA-masticator muscle dose product at 6 months and SA scores at 12 months (p < 0.05). At the optimum cut-off points of 0.38 for the propensity score, the sensitivity was 100% and the specificity was 93% for predicting the prognosis of the trismus patients. The SA score, as determined using MRI, can reflect the radiation injury and correlate to trismus severity. Together with the radiation dose, it could serve as a useful biomarker to predict the outcome and guide the management of trismus following radiation therapy.
C1 [Hsieh, Li-Chun; Tsang, Yuk-Ming] Far Eastern Mem Hosp, Dept Radiol, Div Med Imaging, Taipei, Taiwan.
[Shueng, Pei-Wei; Tien, Hui-Ju; Hsieh, Chen-Hsi] Far Eastern Mem Hosp, Dept Radiol, Div Radiat Oncol, Taipei, Taiwan.
[Liao, Li-Jen; Lo, Wu-Chia] Far Eastern Mem Hosp, Dept Otolaryngol, Taipei, Taiwan.
[Lin, Yu-Chin] Far Eastern Mem Hosp, Dept Internal Med, Div Med Oncol & Hematol, Taipei, Taiwan.
[Tseng, Chien-Fu; Kuo, Ying-Shiung] Far Eastern Mem Hosp, Dept Dent & Oral Surg, Taipei, Taiwan.
[Jhuang, Jie-Yang] Far Eastern Mem Hosp, Dept Anat Pathol, Taipei, Taiwan.
[Hsieh, Chen-Hsi] Natl Yang Ming Univ, Sch Med, Dept Med, Taipei 112, Taiwan.
[Hsieh, Chen-Hsi] Natl Yang Ming Univ, Sch Med, Inst Tradit Med, Taipei 112, Taiwan.
[Wang, Li-Ying] Natl Taiwan Univ, Coll Med, Sch & Grad Inst Phys Therapy, Taipei 10764, Taiwan.
[Shueng, Pei-Wei] Natl Def Med Ctr, Dept Radiat Oncol, Taipei, Taiwan.
[Chen, John W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Cambridge, MA 02138 USA.
[Chen, John W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Cambridge, MA 02138 USA.
[Hsieh, Li-Chun] Natl Taiwan Univ, Ctr Syst Biol, Inst Mol & Cellular Biol, Dept Life Sci, Taipei 10764, Taiwan.
[Juan, Hsueh-Fen] Natl Taiwan Univ, Grad Inst Biomed Elect & Bioinformat, Taipei 10764, Taiwan.
[Hsieh, Li-Chun; Juan, Hsueh-Fen] Taipei Med Univ Hosp, Med Imaging Ctr, Taipei, Taiwan.
RP Hsieh, CH (reprint author), Far Eastern Mem Hosp, Dept Radiol, Div Radiat Oncol, Taipei, Taiwan.
EM chenciab@gmail.com
OI WANG, LI-YING/0000-0003-3075-6872; JUAN, HSUEH-FEN/0000-0003-4876-3309
FU Far Eastern Memorial Hospital [FEMH-2012-C-055, FEMH
101-2314-B-418-010-MY3]
FX This work was supported by the Far Eastern Memorial Hospital grants
(FEMH-2012-C-055; FEMH 101-2314-B-418-010-MY3). The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 25
TC 6
Z9 6
U1 1
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 21
PY 2014
VL 9
IS 3
AR e92561
DI 10.1371/journal.pone.0092561
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6GL
UT WOS:000333355300098
PM 24658376
ER
PT J
AU Subudhi, AW
Bourdillon, N
Bucher, J
Davis, C
Elliott, JE
Eutermoster, M
Evero, O
Fan, JL
Houten, SJV
Julian, CG
Kark, J
Kark, S
Kayser, B
Kern, JP
Kim, SE
Lathan, C
Laurie, SS
Lovering, AT
Paterson, R
Polaner, DM
Ryan, BJ
Spira, JL
Tsao, JW
Wachsmuth, NB
Roach, RC
AF Subudhi, Andrew W.
Bourdillon, Nicolas
Bucher, Jenna
Davis, Christopher
Elliott, Jonathan E.
Eutermoster, Morgan
Evero, Oghenero
Fan, Jui-Lin
Jameson-Van Houten, Sonja
Julian, Colleen G.
Kark, Jonathan
Kark, Sherri
Kayser, Bengt
Kern, Julia P.
Kim, See Eun
Lathan, Corinna
Laurie, Steven S.
Lovering, Andrew T.
Paterson, Ryan
Polaner, David M.
Ryan, Benjamin J.
Spira, James L.
Tsao, Jack W.
Wachsmuth, Nadine B.
Roach, Robert C.
TI AltitudeOmics: The Integrative Physiology of Human Acclimatization to
Hypobaric Hypoxia and Its Retention upon Reascent
SO PLOS ONE
LA English
DT Article
ID ACUTE MOUNTAIN-SICKNESS; OPERATION EVEREST-II; PULMONARY GAS-EXCHANGE;
PLASMA-VOLUME EXPANSION; RED-CELL MASS; COGNITIVE PERFORMANCE; EXTREME
ALTITUDE; OXYGEN-TRANSPORT; SIMULATED ASCENT; CARDIAC-OUTPUT
AB An understanding of human responses to hypoxia is important for the health of millions of people worldwide who visit, live, or work in the hypoxic environment encountered at high altitudes. In spite of dozens of studies over the last 100 years, the basic mechanisms controlling acclimatization to hypoxia remain largely unknown. The AltitudeOmics project aimed to bridge this gap. Our goals were 1) to describe a phenotype for successful acclimatization and assess its retention and 2) use these findings as a foundation for companion mechanistic studies. Our approach was to characterize acclimatization by measuring changes in arterial oxygenation and hemoglobin concentration [Hb], acute mountain sickness (AMS), cognitive function, and exercise performance in 21 subjects as they acclimatized to 5260 m over 16 days. We then focused on the retention of acclimatization by having subjects reascend to 5260 m after either 7 (n = 14) or 21 (n = 7) days at 1525 m. At 16 days at 5260 m we observed: 1) increases in arterial oxygenation and [Hb] (compared to acute hypoxia: PaO2 rose 964 mmHg to 45 +/- 4 while PaCO2 dropped a further 6 +/- 3 mmHg to 21 +/- 3, and [Hb] rose 1.8 +/- 0.7 g/dL to 16 +/- 2 g/dL; 2) no AMS; 3) improved cognitive function; and 4) improved exercise performance by 8 +/- 8% (all changes p<0.01). Upon reascent, we observed retention of arterial oxygenation but not [Hb], protection from AMS, retention of exercise performance, less retention of cognitive function; and noted that some of these effects lasted for 21 days. Taken together, these findings reveal new information about retention of acclimatization, and can be used as a physiological foundation to explore the molecular mechanisms of acclimatization and its retention.
C1 [Subudhi, Andrew W.; Davis, Christopher; Eutermoster, Morgan; Evero, Oghenero; Jameson-Van Houten, Sonja; Julian, Colleen G.; Kark, Jonathan; Kark, Sherri; Paterson, Ryan; Roach, Robert C.] Univ Colorado, Altitude Res Ctr, Dept Emergency Med, Aurora, CO 80045 USA.
[Subudhi, Andrew W.] Univ Colorado, Dept Biol, Colorado Springs, CO 80907 USA.
[Bourdillon, Nicolas; Fan, Jui-Lin; Kayser, Bengt] Univ Lausanne, Fac Biol & Med, Inst Sports Sci, Lausanne, Switzerland.
[Bourdillon, Nicolas; Fan, Jui-Lin] Univ Lausanne, Fac Biol & Med, Dept Physiol, Lausanne, Switzerland.
[Bucher, Jenna; Elliott, Jonathan E.; Kern, Julia P.; Kim, See Eun; Laurie, Steven S.; Lovering, Andrew T.] Univ Oregon, Dept Human Physiol, Eugene, OR 97403 USA.
[Fan, Jui-Lin] Univ Lausanne, Leman Doctoral Sch Neurosci, Lausanne, Switzerland.
[Lathan, Corinna] AnthroTronix Inc, Silver Spring, MD USA.
[Polaner, David M.] Univ Colorado, Sch Med, Dept Anesthesiol, Aurora, CO USA.
[Polaner, David M.] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO USA.
[Polaner, David M.] Childrens Hosp Colorado, Aurora, CO USA.
[Ryan, Benjamin J.] Univ Colorado, Dept Integrat Physiol, Boulder, CO USA.
[Spira, James L.] Univ Hawaii, US Dept Vet Affairs, Pacific Islands Hlth Care Syst, Natl Ctr PTSD, Honolulu, HI 96822 USA.
[Spira, James L.] Univ Hawaii, John A Burns Sch Med, Dept Psychiat, Honolulu, HI 96822 USA.
[Tsao, Jack W.] US Navy Bur Med & Surg, Wounded Ill & Injured Directorate M9, Falls Church, VA USA.
[Wachsmuth, Nadine B.] Univ Bayreuth, Dept Sports Med Sports Physiol, Bayreuth, Germany.
RP Roach, RC (reprint author), Univ Colorado, Altitude Res Ctr, Dept Emergency Med, Anschutz Med Campus, Aurora, CO 80045 USA.
EM Robert.Roach@ucdenver.edu
RI Kayser, Bengt/M-8643-2013;
OI Kayser, Bengt/0000-0002-9776-7501; Polaner, David/0000-0001-8716-6289;
Elliott, Jonathan/0000-0002-6992-6851
FU United States Department of Defense [W81XWH-11-2-0040 TATRC,
W81XWH-10-2-0114]; National Institutes of Health (NIH)/National Center
for Advancing Translational Sciences Colorado CTSI [UL1 TR000154];
Cardiopulmonary & Respiratory Physiology Laboratory, University of
Oregon; Altitude Research Center; Charles S. Houston Endowed
Professorship, Department of Emergency Medicine, School of Medicine,
University of Colorado Denver
FX The overall AltitudeOmics study was funded, in part, by grants from the
United States Department of Defense (W81XWH-11-2-0040 TATRC to RCR and
W81XWH-10-2-0114 to ATL). The project was also supported, in part, by
National Institutes of Health (NIH)/National Center for Advancing
Translational Sciences Colorado CTSI Grant Number UL1 TR000154. Contents
are the author's sole responsibility and do not necessarily represent
official NIH views. Major additional support came from the
Cardiopulmonary & Respiratory Physiology Laboratory, University of
Oregon; the Altitude Research Center and the Charles S. Houston Endowed
Professorship, Department of Emergency Medicine, School of Medicine,
University of Colorado Denver. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 74
TC 16
Z9 16
U1 0
U2 17
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 21
PY 2014
VL 9
IS 3
AR e92191
DI 10.1371/journal.pone.0092191
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6GL
UT WOS:000333355300059
PM 24658407
ER
PT J
AU Saukkonen, K
Tan, TC
Sharma, A
Channick, RN
Murali, MR
Zukerberg, LR
AF Saukkonen, Kai
Tan, Timothy C.
Sharma, Amita
Channick, Richard N.
Murali, Mandakolathur R.
Zukerberg, Lawrence R.
TI Case 9-2014: A 34-Year-Old Woman with Increasing Dyspnea
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID CONNECTIVE-TISSUE DISEASE; SYSTEMIC-LUPUS-ERYTHEMATOSUS;
PULMONARY-HYPERTENSION; CLASSIFICATION; CRITERIA
C1 [Saukkonen, Kai; Tan, Timothy C.; Channick, Richard N.; Murali, Mandakolathur R.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Sharma, Amita] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Zukerberg, Lawrence R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Saukkonen, Kai; Tan, Timothy C.; Channick, Richard N.; Murali, Mandakolathur R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Sharma, Amita] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Zukerberg, Lawrence R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Saukkonen, K (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
FU Actelion Pharmaceuticals; Bayer; United Therapeutics
FX Dr. Channick reports receiving consulting fees and grant support from
Actelion Pharmaceuticals, Bayer, and United Therapeutics. No other
potential conflict of interest relevant to this article was reported.
NR 14
TC 3
Z9 3
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 20
PY 2014
VL 370
IS 12
BP 1149
EP 1157
DI 10.1056/NEJMcpc1305992
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA AD2HA
UT WOS:000333054000012
PM 24645948
ER
PT J
AU Weinstein, JN
Akbani, R
Broom, BM
Wang, WY
Verhaak, RGW
McConkey, D
Lerner, S
Morgan, M
Creighton, CJ
Smith, C
Kwiatkowski, DJ
Cherniack, AD
Kim, J
Pedamallu, CS
Noble, MS
Al-Ahmadie, HA
Reuter, VE
Rosenberg, JE
Bajorin, DF
Bochner, BH
Solit, DB
Koppie, T
Robinson, B
Gordenin, DA
Fargo, D
Klimczak, LJ
Roberts, SA
Au, J
Laird, PW
Hinoue, T
Schultz, N
Ramirez, R
Hansel, D
Hoadley, KA
Kim, WY
Damrauer, JS
Baylin, SB
Mungall, AJ
Robertson, AG
Chu, A
Kwiatkowski, DJ
Sougnez, C
Cibulskis, K
Lichtenstein, L
Sivachenko, A
Stewart, C
Lawrence, MS
Getz, G
Lander, E
Gabriel, SB
Creighton, CJ
Donehower, L
Cherniack, AD
Kim, J
Carter, SL
Saksena, G
Schumacher, SE
Sougnez, C
Freeman, SS
Jung, J
Pedamallu, CS
Bhatt, AS
Pugh, T
Getz, G
Beroukhim, R
Gabriel, SB
Meyerson, M
Mungall, AJ
Robertson, AG
Chu, A
Ally, A
Balasundaram, M
Butterfield, YSN
Dhalla, N
Hirst, C
Holt, RA
Jones, SJM
Lee, D
Li, HYI
Marra, MA
Mayo, M
Moore, RA
Schein, JE
Sipahimalani, P
Tam, A
Thiessen, N
Wong, T
Wye, N
Bowlby, R
Chuah, E
Guin, R
Jones, SJM
Marra, MA
Hinoue, T
Shen, H
Bootwalla, MS
Triche, T
Lai, PH
Van den Berg, DJ
Weisenberger, DJ
Laird, PW
Hansel, D
Hoadley, KA
Balu, S
Bodenheimer, T
Damrauer, JS
Hoyle, AP
Jefferys, SR
Meng, SW
Mose, LE
Simons, JV
Soloway, MG
Wu, JY
Kim, WY
Parker, JS
Hayes, DN
Roach, J
Buda, E
Jones, CD
Mieczkowski, PA
Tan, DH
Veluvolu, U
Waring, S
Auman, JT
Perou, CM
Wilkerson, MD
Santoso, N
Parfenov, M
Ren, XJ
Pantazi, A
Hadjipanayis, A
Seidman, J
Kucherlapati, R
Lee, S
Yang, LX
Park, PJ
Baylin, SB
Xu, AW
Protopopov, A
Zhang, JH
Bristow, C
Mahadeshwar, HS
Seth, S
Song, XZ
Tang, JB
Zeng, D
Chin, LD
Guo, C
Weinstein, JN
Akbani, R
Broom, BM
McConkey, D
Casasent, TD
Liu, WB
Ju, ZL
Motter, T
Peng, B
Ryan, M
Wang, WY
Verhaak, RGW
Su, XP
Yang, JY
Lorenzi, PL
Yao, H
Zhang, NX
Zhang, JX
Mills, GB
Kim, J
Noble, MS
Cho, J
DiCara, D
Frazer, S
Gehlenborg, N
Heiman, DI
Lin, P
Liu, YC
Stojanov, P
Voet, D
Zhang, HL
Zou, LH
Chin, LD
Getz, G
Bernard, B
Kreisberg, D
Reynolds, S
Rovira, H
Shmulevich, I
Ramirez, R
Schultz, N
Gao, JJ
Jacobsen, A
Aksoy, BA
Antipin, Y
Ciriello, G
Dresdner, G
Gross, B
Lee, W
Reva, B
Shen, RL
Sinha, R
Sumer, SO
Weinhold, N
Ladanyi, M
Sander, C
Benz, C
Carlin, D
Haussler, D
Ng, S
Paull, EO
Stuart, J
Zhu, J
Liu, YX
Zhang, W
Taylor, BS
Lichtenberg, TM
Zmuda, E
Barr, T
Black, AD
George, M
Hanf, B
Helsel, C
McAllister, C
Ramirez, NC
Tabler, TR
Weaver, S
Wise, L
Bowen, J
Gastier-Foster, JM
Weinstein, JN
Lerner, S
Jian, WG
Tello, S
Ittman, M
Castro, P
McClenden, WD
Morgan, M
Gibbs, R
Liu, YC
Saller, C
Tarvin, K
DiPiero, JM
Owens, J
Bollag, R
Li, Q
Weinberger, P
Czerwinski, C
Huelsenbeck-Dill, L
Iacocca, M
Petrelli, N
Rabeno, B
Swanson, P
Shelton, T
Curley, E
Gardner, J
Mallery, D
Penny, R
Bang, NV
Hanh, PT
Kohl, B
Le, XV
Phu, BD
Thorp, R
Tien, NV
Vinh, LQ
Sandusky, G
Burks, E
Christ, K
Gee, J
Holway, A
Moinzadeh, A
Sorcini, A
Sullivan, T
Al-Ahmadie, HA
Bajorin, DF
Bochner, BH
Garcia-Grossman, IR
Regazzi, AM
Solit, DB
Rosenberg, JE
Reuter, VE
Koppie, T
Boice, L
Rathmell, WK
Thorne, L
Bastacky, S
Davies, B
Dhir, R
Gingrich, J
Hrebinko, R
Maranchie, J
Nelson, J
Parwani, A
Bshara, W
Gaudioso, C
Morrison, C
Alexopoulou, V
Bartlett, J
Engel, J
Kodeeswaran, S
Antic, T
O'Donnell, PH
Smith, ND
Steinberg, GD
Egea, S
Gomez-Fernandez, C
Herbert, L
Jorda, M
Soloway, M
Beaver, A
Carter, S
Kapur, P
Lewis, C
Lotan, Y
Robinson, B
Hansel, D
Guo, C
Bondaruk, J
Czerniak, B
Akbani, R
Broom, BM
Liu, YX
Zhang, W
Weinstein, JN
Lerner, S
Morgan, M
Kim, J
Cherniack, AD
Freeman, SS
Pedamallu, CS
Noble, MS
Kwiatkowski, DJ
Al-Ahmadie, HA
Bajorin, DF
Bochner, BH
Solit, DB
Rosenberg, JE
Reuter, VE
Koppie, T
Robinson, B
Skinner, E
Ramirez, R
Schultz, N
Hansel, D
Kim, WY
Guo, C
Bondaruk, J
Aldape, K
Czerniak, B
Jensen, MA
Kahn, AB
Pihl, TD
Pot, DA
Srinivasan, D
Wan, YH
Ferguson, ML
Zenklusen, JC
Davidsen, T
Demchok, JA
Shaw, KRM
Sheth, M
Tarnuzzer, R
Wang, ZN
Yang, LM
Hutter, C
Ozenberger, BA
Sofia, HJ
Eley, G
AF Weinstein, John N.
Akbani, Rehan
Broom, Bradley M.
Wang, Wenyi
Verhaak, Roeland G. W.
McConkey, David
Lerner, Seth
Morgan, Margaret
Creighton, Chad J.
Smith, Carolyn
Kwiatkowski, David J.
Cherniack, Andrew D.
Kim, Jaegil
Pedamallu, Chandra Sekhar
Noble, Michael S.
Al-Ahmadie, Hikmat A.
Reuter, Victor E.
Rosenberg, Jonathan E.
Bajorin, Dean F.
Bochner, Bernard H.
Solit, David B.
Koppie, Theresa
Robinson, Brian
Gordenin, Dmitry A.
Fargo, David
Klimczak, Leszek J.
Roberts, Steven A.
Au, Jessie
Laird, Peter W.
Hinoue, Toshinori
Schultz, Nikolaus
Ramirez, Ricardo
Hansel, Donna
Hoadley, Katherine A.
Kim, William Y.
Damrauer, Jeffrey S.
Baylin, Stephen B.
Mungall, Andrew J.
Robertson, A. Gordon
Chu, Andy
Kwiatkowski, David J.
Sougnez, Carrie
Cibulskis, Kristian
Lichtenstein, Lee
Sivachenko, Andrey
Stewart, Chip
Lawrence, Michael S.
Getz, Gad
Lander, Eric
Gabriel, Stacey B.
Creighton, Chad J.
Donehower, Lawrence
Cherniack, Andrew D.
Kim, Jaegil
Carter, Scott L.
Saksena, Gordon
Schumacher, Steven E.
Sougnez, Carrie
Freeman, Samuel S.
Jung, Joonil
Pedamallu, Chandra Sekhar
Bhatt, Ami S.
Pugh, Trevor
Getz, Gad
Beroukhim, Rameen
Gabriel, Stacey B.
Meyerson, Matthew
Mungall, Andrew J.
Robertson, A. Gordon
Chu, Andy
Ally, Adrian
Balasundaram, Miruna
Butterfield, Yaron S. N.
Dhalla, Noreen
Hirst, Carrie
Holt, Robert A.
Jones, Steven J. M.
Lee, Darlene
Li, Haiyan I.
Marra, Marco A.
Mayo, Michael
Moore, Richard A.
Schein, Jacqueline E.
Sipahimalani, Payal
Tam, Angela
Thiessen, Nina
Wong, Tina
Wye, Natasja
Bowlby, Reanne
Chuah, Eric
Guin, Ranabir
Jones, Steven J. M.
Marra, Marco A.
Hinoue, Toshinori
Shen, Hui
Bootwalla, Moiz S.
Triche, Timothy, Jr.
Lai, Phillip H.
Van den Berg, David J.
Weisenberger, Daniel J.
Laird, Peter W.
Hansel, Donna
Hoadley, Katherine A.
Balu, Saianand
Bodenheimer, Tom
Damrauer, Jeffrey S.
Hoyle, Alan P.
Jefferys, Stuart R.
Meng, Shaowu
Mose, Lisle E.
Simons, Janae V.
Soloway, Mathew G.
Wu, Junyuan
Kim, William Y.
Parker, Joel S.
Hayes, D. Neil
Roach, Jeffrey
Buda, Elizabeth
Jones, Corbin D.
Mieczkowski, Piotr A.
Tan, Donghui
Veluvolu, Umadevi
Waring, Scot
Auman, J. Todd
Perou, Charles M.
Wilkerson, Matthew D.
Santoso, Netty
Parfenov, Michael
Ren, Xiaojia
Pantazi, Angeliki
Hadjipanayis, Angela
Seidman, Jonathan
Kucherlapati, Raju
Lee, Semin
Yang, Lixing
Park, Peter J.
Baylin, Stephen B.
Xu, Andrew Wei
Protopopov, Alexei
Zhang, Jianhua
Bristow, Christopher
Mahadeshwar, Harshad S.
Seth, Sahil
Song, Xingzhi
Tang, Jiabin
Zeng, Dong
Chin, Lynda
Guo, Charles
Weinstein, John N.
Akbani, Rehan
Broom, Bradley M.
McConkey, David
Casasent, Tod D.
Liu, Wenbin
Ju, Zhenlin
Motter, Thomas
Peng, Bo
Ryan, Michael
Wang, Wenyi
Verhaak, Roeland G. W.
Su, Xiaoping
Yang, Ji-Yeon
Lorenzi, Philip L.
Yao, Hui
Zhang, Nianxiang
Zhang, Jiexin
Mills, Gordon B.
Kim, Jaegil
Noble, Michael S.
Cho, Juok
DiCara, Daniel
Frazer, Scott
Gehlenborg, Nils
Heiman, David I.
Lin, Pei
Liu, Yingchun
Stojanov, Petar
Voet, Doug
Zhang, Hailei
Zou, Lihua
Chin, Lynda
Getz, Gad
Bernard, Brady
Kreisberg, Dick
Reynolds, Sheila
Rovira, Hector
Shmulevich, Ilya
Ramirez, Ricardo
Schultz, Nikolaus
Gao, Jianjiong
Jacobsen, Anders
Aksoy, B. Arman
Antipin, Yevgeniy
Ciriello, Giovanni
Dresdner, Gideon
Gross, Benjamin
Lee, William
Reva, Boris
Shen, Ronglai
Sinha, Rileen
Sumer, S. Onur
Weinhold, Nils
Ladanyi, Marc
Sander, Chris
Benz, Christopher
Carlin, Daniel
Haussler, David
Ng, Sam
Paull, Evan O.
Stuart, Joshua
Zhu, Jing
Liu, Yuexin
Zhang, Wei
Taylor, Barry S.
Lichtenberg, Tara M.
Zmuda, Erik
Barr, Thomas
Black, Aaron D.
George, Myra
Hanf, Benjamin
Helsel, Carmen
McAllister, Cynthia
Ramirez, Nilsa C.
Tabler, Teresa R.
Weaver, Stephanie
Wise, Lisa
Bowen, Jay
Gastier-Foster, Julie M.
Weinstein, John N.
Lerner, Seth
Jian, Weiguo
Tello, Sebrina
Ittman, Michael
Castro, Patricia
McClenden, Whitney D.
Morgan, Margaret
Gibbs, Richard
Liu, Yingchun
Saller, Charles
Tarvin, Katherine
DiPiero, Jennifer M.
Owens, Jennifer
Bollag, Roni
Li, Qiang
Weinberger, Paul
Czerwinski, Christine
Huelsenbeck-Dill, Lori
Iacocca, Mary
Petrelli, Nicholas
Rabeno, Brenda
Swanson, Pat
Shelton, Troy
Curley, Erin
Gardner, Johanna
Mallery, David
Penny, Robert
Nguyen Van Bang
Phan Thi Hanh
Kohl, Bernard
Xuan Van Le
Bui Duc Phu
Thorp, Richard
Nguyen Viet Tien
Le Quang Vinh
Sandusky, George
Burks, Eric
Christ, Kimberly
Gee, Jason
Holway, Antonia
Moinzadeh, Alireza
Sorcini, Andrea
Sullivan, Travis
Al-Ahmadie, Hikmat A.
Bajorin, Dean F.
Bochner, Bernard H.
Garcia-Grossman, Ilana R.
Regazzi, Ashley M.
Solit, David B.
Rosenberg, Jonathan E.
Reuter, Victor E.
Koppie, Theresa
Boice, Lori
Rathmell, Wendy Kimryn
Thorne, Leigh
Bastacky, Sheldon
Davies, Benjamin
Dhir, Rajiv
Gingrich, Jeffrey
Hrebinko, Ronald
Maranchie, Jodi
Nelson, Joel
Parwani, Anil
Bshara, Wiam
Gaudioso, Carmelo
Morrison, Carl
Alexopoulou, Vina
Bartlett, John
Engel, Jay
Kodeeswaran, Sugy
Antic, Tatjana
O'Donnell, Peter H.
Smith, Norm D.
Steinberg, Gary D.
Egea, Sophie
Gomez-Fernandez, Carmen
Herbert, Lynn
Jorda, Merce
Soloway, Mark
Beaver, Allison
Carter, Suzie
Kapur, Payal
Lewis, Cheryl
Lotan, Yair
Robinson, Brian
Hansel, Donna
Guo, Charles
Bondaruk, Jolanta
Czerniak, Bogdan
Akbani, Rehan
Broom, Bradley M.
Liu, Yuexin
Zhang, Wei
Weinstein, John N.
Lerner, Seth
Morgan, Margaret
Kim, Jaegil
Cherniack, Andrew D.
Freeman, Samuel S.
Pedamallu, Chandra Sekhar
Noble, Michael S.
Kwiatkowski, David J.
Al-Ahmadie, Hikmat A.
Bajorin, Dean F.
Bochner, Bernard H.
Solit, David B.
Rosenberg, Jonathan E.
Reuter, Victor E.
Koppie, Theresa
Robinson, Brian
Skinner, Eila
Ramirez, Ricardo
Schultz, Nikolaus
Hansel, Donna
Kim, William Y.
Guo, Charles
Bondaruk, Jolanta
Aldape, Kenneth
Czerniak, Bogdan
Jensen, Mark A.
Kahn, Ari B.
Pihl, Todd D.
Pot, David A.
Srinivasan, Deepak
Wan, Yunhu
Ferguson, Martin L.
Zenklusen, Jean Claude
Davidsen, Tanja
Demchok, John A.
Shaw, Kenna R. Mills
Sheth, Margi
Tarnuzzer, Roy
Wang, Zhining
Yang, Liming
Hutter, Carolyn
Ozenberger, Bradley A.
Sofia, Heidi J.
Eley, Greg
CA Canc Genome Atlas Res Network
TI Comprehensive molecular characterization of urothelial bladder carcinoma
SO NATURE
LA English
DT Article
ID HUMAN CANCERS; GENE FUSIONS; TUMOR-GROWTH; MUTATIONS; GENOMES; KINASE;
FGFR
AB Urothelial carcinoma of the bladder is a common malignancy that causes approximately 150,000 deaths per year worldwide. So far, no molecularly targeted agents have been approved for treatment of the disease. As part of The Cancer Genome Atlas project, we report here an integrated analysis of 131 urothelial carcinomasto provide a comprehensive landscape of molecular alterations. There were statistically significant recurrent mutations in 32 genes, including multiple genes involved in cell-cycle regulation, chromatin regulation, and kinase signalling pathways, as well as 9 genes not previously reported as significantly mutated in any cancer. RNA sequencing revealed four expression subtypes, two of which (papillary-like and basal/squamous-like) were also evident in microRNA sequencing and protein data. Whole-genome and RNA sequencing identified recurrent in-frame activating FGFR3-TACC3 fusions and expression or integration of several viruses (including HPV16) that are associated with gene inactivation. Our analyses identified potential therapeutic targets in 69% of the tumours, including 42% with targets in the phosphatidylinositol-3-OH kinase/AKT/mTOR pathway and 45% with targets (including ERBB2) in the RTK/MAPK pathway. Chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far, indicating the future possibility of targeted therapy for chromatin abnormalities.
C1 [Weinstein, John N.; Akbani, Rehan; Broom, Bradley M.; Wang, Wenyi; Verhaak, Roeland G. W.; Liu, Wenbin; Ju, Zhenlin; Motter, Thomas; Peng, Bo; Ryan, Michael; Su, Xiaoping; Yang, Ji-Yeon; Lorenzi, Philip L.; Yao, Hui; Zhang, Nianxiang; Zhang, Jiexin] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
[Liu, Wenbin; Ju, Zhenlin; Yang, Ji-Yeon; Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.
[McConkey, David; Shaw, Kenna R. Mills] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Lerner, Seth; Jian, Weiguo; Tello, Sebrina] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA.
[Morgan, Margaret; Jian, Weiguo; Tello, Sebrina; Ittman, Michael; Castro, Patricia; McClenden, Whitney D.; Gibbs, Richard] Baylor Coll Med, TCRB, Houston, TX 77030 USA.
[Gibbs, Richard] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Creighton, Chad J.; Donehower, Lawrence] Baylor Coll Med, Human Genome Sequencing Ctr, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
[Smith, Carolyn] Baylor Coll Med, Houston, TX 77030 USA.
[Kwiatkowski, David J.; Kwiatkowski, David J.; Cibulskis, Kristian; Lichtenstein, Lee; Sivachenko, Andrey; Stewart, Chip; Lawrence, Michael S.; Getz, Gad; Lander, Eric; Gabriel, Stacey B.; Carter, Scott L.; Saksena, Gordon; Schumacher, Steven E.; Freeman, Samuel S.; Jung, Joonil; Bhatt, Ami S.; Pugh, Trevor; Beroukhim, Rameen; Meyerson, Matthew; Chin, Lynda; Cho, Juok; DiCara, Daniel; Frazer, Scott; Gehlenborg, Nils; Heiman, David I.; Lin, Pei; Liu, Yingchun; Stojanov, Petar; Voet, Doug; Zhang, Hailei; Zou, Lihua] Eli & Edythe L Broad Inst Massachusetts Inst Tech, Cambridge, MA 02142 USA.
[Kwiatkowski, David J.; Casasent, Tod D.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Kwiatkowski, David J.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Bhatt, Ami S.; Pugh, Trevor; Beroukhim, Rameen; Meyerson, Matthew; Stojanov, Petar] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Garcia-Grossman, Ilana R.; Regazzi, Ashley M.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
[Koppie, Theresa] Oregon Hlth & Sci Univ, Dept Urol, Portland, OR 97239 USA.
Cornell Univ, Weill Med Coll, New York, NY 10065 USA.
[Gordenin, Dmitry A.; Fargo, David; Klimczak, Leszek J.; Roberts, Steven A.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Au, Jessie] OptimumTherapeutics LLC, San Diego, CA 92121 USA.
[Shen, Hui; Bootwalla, Moiz S.; Triche, Timothy, Jr.; Lai, Phillip H.; Van den Berg, David J.; Weisenberger, Daniel J.] Univ So Calif, Epigenome Ctr, Los Angeles, CA 90033 USA.
[Schultz, Nikolaus; Ramirez, Ricardo; Gao, Jianjiong; Jacobsen, Anders; Aksoy, B. Arman; Antipin, Yevgeniy; Ciriello, Giovanni; Dresdner, Gideon; Gross, Benjamin; Lee, William; Reva, Boris; Shen, Ronglai; Sinha, Rileen; Sumer, S. Onur; Weinhold, Nils; Ladanyi, Marc; Sander, Chris] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10065 USA.
[Hansel, Donna] UCSD Dept Pathol, La Jolla, CA 92093 USA.
[Hoadley, Katherine A.; Balu, Saianand; Bodenheimer, Tom; Hoyle, Alan P.; Jefferys, Stuart R.; Meng, Shaowu; Mose, Lisle E.; Simons, Janae V.; Soloway, Mathew G.; Wu, Junyuan; Parker, Joel S.; Hayes, D. Neil] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Parker, Joel S.; Perou, Charles M.; Wilkerson, Matthew D.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA.
[Baylin, Stephen B.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Canc Biol Div, Baltimore, MD 21231 USA.
Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Donehower, Lawrence] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA.
[Schumacher, Steven E.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA.
[Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA.
[Mungall, Andrew J.; Chu, Andy; Ally, Adrian; Balasundaram, Miruna; Butterfield, Yaron S. N.; Dhalla, Noreen; Hirst, Carrie; Holt, Robert A.; Jones, Steven J. M.; Lee, Darlene; Li, Haiyan I.; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Wong, Tina; Wye, Natasja; Bowlby, Reanne; Chuah, Eric; Guin, Ranabir] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4S6, Canada.
[Hayes, D. Neil] Univ N Carolina, Dept Internal Med, Div Med Oncol, Chapel Hill, NC 27599 USA.
[Roach, Jeffrey] Univ N Carolina, Res Comp Ctr, Chapel Hill, NC 27599 USA.
[Buda, Elizabeth; Jones, Corbin D.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
[Jones, Corbin D.; Mieczkowski, Piotr A.; Tan, Donghui; Veluvolu, Umadevi; Waring, Scot] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.
[Auman, J. Todd] Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA.
[Santoso, Netty; Parfenov, Michael; Ren, Xiaojia; Pantazi, Angeliki; Hadjipanayis, Angela; Seidman, Jonathan; Kucherlapati, Raju] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Hadjipanayis, Angela; Kucherlapati, Raju; Park, Peter J.; Xu, Andrew Wei] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.
[Lee, Semin; Yang, Lixing; Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA.
[Park, Peter J.] Childrens Hosp, Informat Program, Boston, MA 02115 USA.
[Protopopov, Alexei; Zhang, Jianhua; Bristow, Christopher; Mahadeshwar, Harshad S.; Seth, Sahil; Song, Xingzhi; Tang, Jiabin; Zeng, Dong] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Inst Appl Canc Sci, Houston, TX 77030 USA.
[Guo, Charles; Bondaruk, Jolanta; Czerniak, Bogdan; Aldape, Kenneth] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Bernard, Brady; Kreisberg, Dick; Reynolds, Sheila; Rovira, Hector; Shmulevich, Ilya] Inst Syst Biol, Seattle, WA 98109 USA.
[Benz, Christopher] Buck Inst Res Aging, Novato, CA 94945 USA.
[Carlin, Daniel; Haussler, David; Ng, Sam; Paull, Evan O.; Stuart, Joshua; Zhu, Jing] Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA.
[Liu, Yuexin; Zhang, Wei] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Taylor, Barry S.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA.
[Lichtenberg, Tara M.; Zmuda, Erik; Barr, Thomas; Black, Aaron D.; George, Myra; Hanf, Benjamin; Helsel, Carmen; McAllister, Cynthia; Ramirez, Nilsa C.; Tabler, Teresa R.; Weaver, Stephanie; Wise, Lisa; Bowen, Jay; Gastier-Foster, Julie M.] Nationwide Childrens Hosp, Res Inst, Columbus, OH 43205 USA.
[Ramirez, Nilsa C.; Gastier-Foster, Julie M.] Ohio State Univ, Columbus, OH 43210 USA.
[Ittman, Michael; Castro, Patricia] Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA.
[Saller, Charles; Tarvin, Katherine] Analyt Biol Serv Inc, Wilmington, DE 19801 USA.
[DiPiero, Jennifer M.; Owens, Jennifer] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Bollag, Roni; Li, Qiang; Weinberger, Paul] Georgia Regents Univ, Canc Ctr, Augusta, GA 30912 USA.
[Czerwinski, Christine; Huelsenbeck-Dill, Lori; Iacocca, Mary; Petrelli, Nicholas; Rabeno, Brenda; Swanson, Pat] Christiana Care, Helen F Graham Canc Ctr, Newark, DE 19713 USA.
[Shelton, Troy; Curley, Erin; Gardner, Johanna; Mallery, David; Penny, Robert] Int Genom Consortium, Phoenix, AZ 85004 USA.
[Nguyen Van Bang; Phan Thi Hanh; Kohl, Bernard; Xuan Van Le; Bui Duc Phu; Thorp, Richard; Nguyen Viet Tien; Le Quang Vinh] ILSbio LLC, Chestertown, MD 21620 USA.
Hue Cent Hosp, Hue City, Vietnam.
[Sandusky, George] IU Sch Med, Indianapolis, IN 46202 USA.
[Burks, Eric; Christ, Kimberly; Gee, Jason; Holway, Antonia; Moinzadeh, Alireza; Sorcini, Andrea; Sullivan, Travis] Lahey Hosp & Med Ctr, Burlington, MA 01805 USA.
[Boice, Lori; Rathmell, Wendy Kimryn; Thorne, Leigh] Univ N Carolina, Lineberger Canc Ctr, Chapel Hill, NC 27599 USA.
[Bastacky, Sheldon; Davies, Benjamin; Dhir, Rajiv; Gingrich, Jeffrey; Hrebinko, Ronald; Maranchie, Jodi; Nelson, Joel; Parwani, Anil] Univ Pittsburgh, Pittsburgh, PA 15213 USA.
[Bshara, Wiam; Gaudioso, Carmelo; Morrison, Carl] Roswell Pk Canc Inst, Buffalo, NY 14063 USA.
[Alexopoulou, Vina; Bartlett, John; Engel, Jay; Kodeeswaran, Sugy] St Josephs Healthcare Hamilton, Ontario Tumour Bank, Hamilton, ON L8N 3Z5, Canada.
[Antic, Tatjana; O'Donnell, Peter H.; Smith, Norm D.; Steinberg, Gary D.] Univ Chicago, Chicago, IL 60637 USA.
[Egea, Sophie; Gomez-Fernandez, Carmen; Herbert, Lynn; Jorda, Merce; Soloway, Mark] Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA.
[Beaver, Allison; Carter, Suzie; Kapur, Payal; Lewis, Cheryl; Lotan, Yair] UT Southwestern Med Ctr, Dallas, TX 75390 USA.
[Skinner, Eila] Stanford Univ, Dept Urol, Stanford, CA 94305 USA.
[Jensen, Mark A.; Kahn, Ari B.; Pihl, Todd D.; Pot, David A.; Srinivasan, Deepak; Wan, Yunhu] SRA Int, Fairfax, VA 22033 USA.
[Ferguson, Martin L.] MLF Consulting, Arlington, MA 02474 USA.
[Zenklusen, Jean Claude; Davidsen, Tanja; Demchok, John A.; Shaw, Kenna R. Mills; Sheth, Margi; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming] NCI, Bethesda, MD 20892 USA.
[Hutter, Carolyn; Ozenberger, Bradley A.; Sofia, Heidi J.] NHGRI, Rockville, MD 20852 USA.
[Eley, Greg] Scimentis LLC, Atlanta, GA 30666 USA.
RP Weinstein, JN (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
EM jweinste@mdanderson.org; slerner@bcm.edu; dk@rics.bwh.harvard.edu
RI Laird, Peter/G-8683-2012; Jacobsen, Anders/K-1081-2013; Schein,
Jacquie/G-3674-2015; Weinberger, Paul/B-7007-2008; Jones,
Steven/C-3621-2009; Lee, Semin/S-2629-2016; Marra, Marco/B-5987-2008;
Holt, Robert/C-3303-2009;
OI Gordenin, Dmitry/0000-0002-8399-1836; Maranchie,
Jodi/0000-0002-8534-9468; Seth, Sahil/0000-0003-4579-3959; Pot,
David/0000-0002-1480-9826; Sinha, Rileen/0000-0001-5497-5055; Perou,
Charles/0000-0001-9827-2247; Gehlenborg, Nils/0000-0003-0327-8297;
Rosenberg, Jonathan/0000-0003-2637-4249; Triche,
Tim/0000-0001-5665-946X; Jacobsen, Anders/0000-0001-6847-4980;
Weinberger, Paul/0000-0002-5885-2631; Lee, Semin/0000-0002-9015-6046;
Kohl, Bernard/0000-0002-4610-0934; Schultz,
Nikolaus/0000-0002-0131-4904; Al-Ahmadie, Hikmat/0000-0002-2938-6627
FU United States National Institutes of Health [U54 HG003273, U54 HG003067,
U54 HG003079, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843,
U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867,
U24 CA143882, U24 CA143883, U24 CA144025, P01 CA120964]
FX We are grateful to all of the patients and families who contributed to
this study, as well as C. Gunter and L. Chastain for scientific editing
and M. Sheth, J. Zhang and C. Ron Bouchard for administrative support.
This work was supported by the following grants from the United States
National Institutes of Health: U54 HG003273, U54 HG003067, U54 HG003079,
U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845,
U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882,
U24 CA143883, U24 CA144025 and P01 CA120964. Additional personnel and
funding sources are acknowledged in the Supplementary Information.
NR 39
TC 379
Z9 383
U1 15
U2 126
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 20
PY 2014
VL 507
IS 7492
BP 315
EP 322
DI 10.1038/nature12965
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD1YG
UT WOS:000333029000025
ER
PT J
AU DePeralta, DK
Hoang, MP
Tanabe, KK
AF DePeralta, Danielle K.
Hoang, Mai P.
Tanabe, Kenneth K.
TI Approaches to Regional Nodes in Patients With Melanoma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID SENTINEL LYMPH-NODES; RANDOMIZED SURGICAL TRIAL; EARLY-STAGE MELANOMA;
POSITIVE MELANOMA; MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; MULTICENTER
TRIAL; NODAL OBSERVATION; EXCISION MARGINS; SCORING SYSTEM
C1 [DePeralta, Danielle K.; Tanabe, Kenneth K.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[DePeralta, Danielle K.; Hoang, Mai P.; Tanabe, Kenneth K.] Harvard Univ, Sch Med, Boston, MA USA.
[Hoang, Mai P.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP DePeralta, DK (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
EM ktanabe@partners.org
NR 28
TC 2
Z9 2
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 20
PY 2014
VL 32
IS 9
BP 881
EP 885
DI 10.1200/JCO.2013.52.3571
PG 5
WC Oncology
SC Oncology
GA AG0XA
UT WOS:000335137900017
PM 24516017
ER
PT J
AU Vaz-Luis, I
Keating, NL
Lin, NU
Lii, HC
Winer, EP
Freedman, RA
AF Vaz-Luis, Ines
Keating, Nancy L.
Lin, Nancy U.
Lii, Huichuan
Winer, Eric P.
Freedman, Rachel A.
TI Duration and Toxicity of Adjuvant Trastuzumab in Older Patients With
Early-Stage Breast Cancer: A Population-Based Study
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID SEER-MEDICARE DATA; HEART-FAILURE; COMORBIDITY INDEX; NSABP B-31;
FOLLOW-UP; CHEMOTHERAPY; VALIDATION; ONCOGENE; THERAPY; TRIAL
AB Purpose Few data are available regarding adjuvant trastuzumab use in older women with early-stage breast cancer. We examined rates and predictors of adjuvant trastuzumab completion and cardiac events in this population.
Patients and Methods We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data to identify patients age 66 years with stage I to III breast cancer diagnosed between 2005 and 2009 who received trastuzumab. Completion of trastuzumab was defined as receipt of more than 270 days of therapy. We used multivariable logistic regression to examine patient, clinical, and geographic characteristics associated with trastuzumab completion. We also examined rates of hospital admissions for cardiac events.
Results Among 2,028 women, most (71.2%) were younger than age 76 years and had a comorbidity score of 0 (66.8%); 85.2% received trastuzumab with chemotherapy. Overall, 1,656 women (81.7%) completed trastuzumab. Older patients and those with more comorbidity had lower odds of treatment completion (odds ratio [OR], 0.40 [95% CI, 0.30 to 0.55] for age 80 years v age 66 to 70 years; OR, 0.65 [95% CI, 0.49 to 0.88] for comorbidity score of 2 v 0). During treatment, 73 patients (3.6%) were hospitalized for cardiac events (2.6% of those who completed trastuzumab v 8.1% of those who did not; P < .001).
Conclusion Most older patients who initiated adjuvant trastuzumab completed therapy. Age and comorbidity were among factors that were associated with treatment completion, and rates of significant cardiac events were higher in those who did not complete therapy. Further exploration of toxicities and optimal treatments for older women with human epidermal growth factor receptor 2-positive breast cancer are warranted.
C1 [Vaz-Luis, Ines; Lin, Nancy U.; Winer, Eric P.; Freedman, Rachel A.] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Keating, Nancy L.] Harvard Univ, Sch Med, Boston, MA USA.
[Keating, Nancy L.; Lii, Huichuan] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Vaz-Luis, Ines] Inst Mol Med, Lisbon, Portugal.
RP Freedman, RA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.
EM Rachel_Freedman@dfci.harvard.edu
FU NCI NIH HHS [N01PC35139, P50 CA089393, N01PC35136, N02 PC015105]
NR 22
TC 25
Z9 25
U1 0
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 20
PY 2014
VL 32
IS 9
BP 927
EP +
DI 10.1200/JCO.2013.51.1261
PG 9
WC Oncology
SC Oncology
GA AG0XA
UT WOS:000335137900020
PM 24516021
ER
PT J
AU Zhou, YF
Springer, TA
AF Zhou, Yan-Feng
Springer, Timothy A.
TI Highly reinforced structure of a C-terminal dimerization domain in von
Willebrand factor
SO BLOOD
LA English
DT Article
ID GROWTH-FACTOR; DENSITY MODIFICATION; PROTEINS; ALIGNMENT; ADHESION;
SEQUENCE; DATABASE; QUALITY; SYSTEM; FAMILY
AB The C-terminal cystine knot (CK) (CTCK) domain in von Willebrand factor (VWF) mediates dimerization of proVWF in the endoplasmic reticulum and is essential for long multimers required for hemostatic function. The CTCK dimer crystal structure reveals highly elongated monomers with 2 beta-ribbons and 4 intra-chain disulfides, including 3 in the CK. Dimerization buries an extensive interface of 1500 A(2) corresponding to 32% of the surface of each monomer and forms a super beta-sheet and 3 inter-chain disulfides. The shape, dimensions, and N-terminal connections of the crystal structure agree perfectly with previous electron microscopic images of VWF dimeric bouquets with the CTCK dimer forming a down-curved base. The dimer interface is suited to resist hydrodynamic force and disulfide reduction. CKs in each monomer flank the 3 inter-chain disulfides, and their presence in beta-structures with dense backbone hydrogen bonds creates a rigid, highly crosslinked interface. The structure reveals the basis for von Willebrand disease phenotypes and the fold and disulfide linkages for CTCK domains in diverse protein families involved in barrier function, eye and inner ear development, insect coagulation and innate immunity, axon guidance, and signaling in extracellular matrices.
C1 [Springer, Timothy A.] Harvard Univ, Sch Med, Program Cellular & Mol Med, Childrens Hosp Boston, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
RP Springer, TA (reprint author), Harvard Univ, Sch Med, Program Cellular & Mol Med, Childrens Hosp Boston, Boston, MA 02115 USA.
EM timothy.springer@childrens.harvard.edu
NR 40
TC 12
Z9 12
U1 0
U2 7
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAR 20
PY 2014
VL 123
IS 12
BP 1785
EP 1793
DI 10.1182/blood-2013-11-523639
PG 9
WC Hematology
SC Hematology
GA AH0ZH
UT WOS:000335848800011
PM 24394662
ER
PT J
AU Richardson, PG
Siegel, DS
Vij, R
Hofmeister, CC
Baz, R
Jagannath, S
Chen, C
Lonial, S
Jakubowiak, A
Bahlis, N
Song, K
Belch, A
Raje, N
Shustik, C
Lentzsch, S
Lacy, M
Mikhael, J
Matous, J
Vesole, D
Chen, M
Zaki, MH
Jacques, C
Yu, ZN
Anderson, KC
AF Richardson, Paul G.
Siegel, David S.
Vij, Ravi
Hofmeister, Craig C.
Baz, Rachid
Jagannath, Sundar
Chen, Christine
Lonial, Sagar
Jakubowiak, Andrzej
Bahlis, Nizar
Song, Kevin
Belch, Andrew
Raje, Noopur
Shustik, Chaim
Lentzsch, Suzanne
Lacy, Martha
Mikhael, Joseph
Matous, Jeffrey
Vesole, David
Chen, Min
Zaki, Mohamed H.
Jacques, Christian
Yu, Zhinuan
Anderson, Kenneth C.
TI Pomalidomide alone or in combination with low-dose dexamethasone in
relapsed and refractory multiple myeloma: a randomized phase 2 study
SO BLOOD
LA English
DT Article
ID LENALIDOMIDE PLUS DEXAMETHASONE; THALIDOMIDE ANALOGS; II TRIALS;
BORTEZOMIB; THERAPY; CC-4047; DRUGS; IMIDS; CELLS
AB This multicenter, open-label, randomized phase 2 study assessed the efficacy and safety of pomalidomide (POM) with/without low-dose dexamethasone (LoDEX) in patients with relapsed/refractory multiple myeloma (RRMM). Patients who had received >= 2 prior therapies (including lenalidomide [LEN] and bortezomib [BORT]) and had progressed within 60 days of their last therapy were randomized to POM (4 mg/day on days 1-21 of each 28-day cycle) with/without LoDEX (40 mg/week). The primary end point was progression-free survival (PFS). In total, 221 patients (median 5 prior therapies, range 1-13) received POM+LoDEX(n = 113) or POM(n = 108). With a median follow-up of 14.2 months, median PFS was 4.2 and 2.7 months (hazard ratio = 0.68, P = .003), overall response rates (ORRs) were 33% and 18% (P = .013), median response duration was 8.3 and 10.7 months, and median overall survival (OS) was 16.5 and 13.6 months, respectively. Refractoriness to LEN, or resistance to both LEN and BORT, did not affect outcomes with POM+LoDEX (median PFS 3.8 months for both; ORRs 30% and 31%; and median OS 16 and 13.4 months). Grade 3-4 neutropenia occurred in 41% (POM+LoDEX) and 48% (POM); no grade 3-4 peripheral neuropathy was reported. POM+LoDEX was effective and generally well tolerated and provides an important new treatment option for RRMM patients who have received multiple prior therapies. This trial was registered at www.clinicaltrials.gov as #NCT00833833.
C1 [Richardson, Paul G.; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Siegel, David S.; Vesole, David] John Theurer Canc Ctr, Hackensack, NJ USA.
[Vij, Ravi] Washington Univ, Sch Med, St Louis, MO USA.
[Hofmeister, Craig C.] Ohio State Univ, Columbus, OH 43210 USA.
[Baz, Rachid] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
[Jagannath, Sundar] Mt Sinai Med Ctr, New York, NY 10029 USA.
[Chen, Christine] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
[Lonial, Sagar] Emory Univ, Sch Med, Atlanta, GA USA.
[Jakubowiak, Andrzej] Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
[Bahlis, Nizar] Univ Calgary, Calgary, AB, Canada.
[Song, Kevin] Vancouver Gen Hosp, Vancouver, BC, Canada.
[Belch, Andrew] Univ Alberta, Edmonton, AB T6G 2M7, Canada.
[Raje, Noopur] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Shustik, Chaim] Royal Victoria Hosp, Montreal, PQ H3A 1A1, Canada.
[Lentzsch, Suzanne] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA.
[Lacy, Martha] Mayo Clin, Rochester, MN USA.
[Mikhael, Joseph] Mayo Clinic Scottsdale, Scottsdale, AZ USA.
[Matous, Jeffrey] Colorado Blood Canc Inst, Denver, CO USA.
[Chen, Min; Zaki, Mohamed H.; Jacques, Christian; Yu, Zhinuan] Celgene Corp, Summit, NJ USA.
RP Richardson, PG (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA.
EM paul_richardson@dfci.harvard.edu
FU Celgene Corporation
FX This study was funded by Celgene Corporation. The authors are fully
responsible for all content and editorial decisions for this manuscript.
NR 40
TC 106
Z9 110
U1 1
U2 8
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAR 20
PY 2014
VL 123
IS 12
BP 1826
EP 1832
DI 10.1182/blood-2013-11-538835
PG 7
WC Hematology
SC Hematology
GA AH0ZH
UT WOS:000335848800016
PM 24421329
ER
PT J
AU Martinez-Andrade, GO
Cespedes, EM
Rifas-Shiman, SL
Romero-Quechol, G
Gonzalez-Unzaga, MA
Benitez-Trejo, MA
Flores-Huerta, S
Horan, C
Haines, J
Taveras, EM
Perez-Cuevas, R
Gillman, MW
AF Oliva Martinez-Andrade, Gloria
Cespedes, Elizabeth M.
Rifas-Shiman, Sheryl L.
Romero-Quechol, Guillermina
Aurelio Gonazlez-Unzaga, Marco
Amalia Benitez-Trejo, Maria
Flores-Huerta, Samuel
Horan, Chrissy
Haines, Jess
Taveras, Elsie M.
Perez-Cuevas, Ricardo
Gillman, Matthew W.
TI Feasibility and impact of Creciendo Sanos, a clinic-based pilot
intervention to prevent obesity among preschool children in Mexico City
SO BMC PEDIATRICS
LA English
DT Article
DE Obesity prevention; Intervention; Trial; Pediatrics; Primary care;
Mexico; Preschool
ID RANDOMIZED CONTROLLED-TRIAL; CHILDHOOD OBESITY; PRIMARY-CARE;
YOUNG-CHILDREN; OVERWEIGHT; PERCEPTIONS; COMPONENTS; BEHAVIORS;
SETTINGS; PROGRAMS
AB Background: Mexico has the highest adult overweight and obesity prevalence in the Americas; 23.8% of children < 5 years old are at risk for overweight and 9.7% are already overweight or obese. Creciendo Sanos was a pilot intervention to prevent obesity among preschoolers in Instituto Mexicano del Seguro Social (IMSS) clinics.
Methods: We randomized 4 IMSS primary care clinics to either 6 weekly educational sessions promoting healthful nutrition and physical activity or usual care. We recruited 306 parent-child pairs: 168 intervention, 138 usual care. Children were 2 5 years old with WHO body mass index (BMI) z score 0 3. We measured children's height and weight and parents reported children's diet and physical activity at baseline and 3 and 6-month follow-up. We analyzed behavioral and BMI outcomes with generalized mixed models incorporating multiple imputation for missing values.
Results: 93 (55%) intervention and 96 (70%) usual care families completed 3 and 6-month follow-up. At 3 months, intervention v. usual care children increased vegetables by 6.3 servings/week (95% CI, 1.8, 10.8). In stratified analyses, intervention participants with high program adherence (5-6 sessions) decreased snacks and screen time and increased vegetables v. usual care. No further effects on behavioral outcomes or BMI were observed. Transportation time and expenses were barriers to adherence. 90% of parents who completed the post-intervention survey were satisfied with the program.
Conclusions: Although satisfaction was high among participants, barriers to participation and retention included transportation cost and time. In intention to treat analyses, we found intervention effects on vegetable intake, but not other behaviors or BMI.
C1 [Oliva Martinez-Andrade, Gloria; Romero-Quechol, Guillermina; Aurelio Gonazlez-Unzaga, Marco] Inst Mexicano Seguro Social, Unidad Invest Epidemiol & Serv Salud, Mexico City 06720, DF, Mexico.
[Cespedes, Elizabeth M.; Rifas-Shiman, Sheryl L.; Horan, Chrissy; Gillman, Matthew W.] Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care Inst, Obes Prevent Program,Dept Populat Med, Boston, MA 02215 USA.
[Cespedes, Elizabeth M.; Taveras, Elsie M.; Gillman, Matthew W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Amalia Benitez-Trejo, Maria; Flores-Huerta, Samuel] Hosp Infantil Mexico Dr Federico Gomez, Secretaria Salud, Commun Hlth Dept, Mexico City 06720, DF, Mexico.
[Haines, Jess] Univ Guelph, Dept Family Relat & Appl Nutr, Guelph, ON N1G 2W1, Canada.
[Taveras, Elsie M.] MassGen Hosp Children, Div Gen Pediat, Boston, MA 02114 USA.
[Perez-Cuevas, Ricardo] Banco Inter Amer Desarrollo, Div Protecc Social & Salud, Mexico City 6600, DF, Mexico.
RP Cespedes, EM (reprint author), Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care Inst, Obes Prevent Program,Dept Populat Med, 133 Brookline Ave,3rd Floor, Boston, MA 02215 USA.
EM emc611@mail.harvard.edu
OI Cespedes Feliciano, Elizabeth/0000-0003-1192-4017
FU NIDDK NIH HHS [T32 DK007703]
NR 34
TC 5
Z9 5
U1 0
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2431
J9 BMC PEDIATR
JI BMC Pediatr.
PD MAR 20
PY 2014
VL 14
AR 77
DI 10.1186/1471-2431-14-77
PG 15
WC Pediatrics
SC Pediatrics
GA AG4UD
UT WOS:000335414900002
PM 24649831
ER
PT J
AU Cao, HJ
Wu, SL
Li, SQ
Zhao, HY
Ruan, CY
Wu, YT
Xing, AJ
Li, KB
Chen, J
Yang, XC
Cai, J
AF Cao Huijun
Wu Shouling
Li Shuqiang
Zhao Haiyan
Ruan Chunyu
Wu Yuntao
Xing Aijun
Li Kuibao
Chen Jin
Yang Xinchun
Cai Jun
TI Characterization and influencing factors of visit-to-visit blood
pressure variability of the population in a northern Chinese industrial
city
SO CHINESE MEDICAL JOURNAL
LA English
DT Article
DE blood pressure variability; age; influencing factors
ID DIAGNOSED HYPERTENSION; EPISODIC HYPERTENSION; CARDIOVASCULAR RISK;
ORGAN DAMAGE
AB Background Blood pressure variability (BPV) is a reliable prognostic factor for cardiovascular events. Currently there is a worldwide lack of large sample size studies in visit-to-visit BPV. Based on the Kailuan Study, we analyzed the visit-to-visit BPV of patients to investigate the range and influencing factors of BPV.
Methods In 11 hospitals in the Kailuan Company, 4 441 patients received routine health checkups. Physical examination measured blood pressure (BP), body height, body weight, and waist circumference, and body mass index was calculated. Blood samples were analyzed for plasma total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), and high-sensitivity c-reactive protein (hs-CRP).
Results The effect of gender on systolic BPV was investigated. The average systolic BPV was 10.35 mmHg (1 mmHg= 0.133 kPa) overall, 10.54 mmHg in males and 10.06 mmHg in females. Multivariate Logistic regression analysis revealed that the age (RR=1.022), systolic BP (SBP, RR=1.007), LDL-C (RR=1.098), and history of hypertension (RR=1.273) were significant risk factors for higher systolic BPV. We found that aging (RR=1.022), increased SBP (RR=1.007), and a history of hypertension (RR=1.394) were determinants of systolic BPV in males. The risk factors for systolic BPV of females were aging (RR=1.017), increased SBP (RR=1.009), increased LDL (RR=1.136), and increased TG (RR= 1.157).
Conclusion Our findings indicated that the systolic BPV is closely associated with age, SBP and history of hypertension.
C1 [Cao Huijun; Li Kuibao; Chen Jin; Yang Xinchun; Cai Jun] Capital Med Univ, Chaoyang Hosp, Dept Cardiol, Beijing 100020, Peoples R China.
[Wu Shouling; Zhao Haiyan; Ruan Chunyu; Wu Yuntao; Xing Aijun] Hebei United Univ, Kailuan Hosp, Dept Cardiol, Tangshan 063000, Hebei, Peoples R China.
[Li Shuqiang] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
RP Yang, XC (reprint author), Capital Med Univ, Chaoyang Hosp, Dept Cardiol, 8th Gongtinanlu Rd, Beijing 100020, Peoples R China.
EM yangxc2010@hotmail.com
FU National Natural Science Foundation of China [81170244]; Beijing Nova
Program [2009B39]; Beijing Natural Science Foundation [7102057]
FX This work is supported by grants from the National Natural Science
Foundation of China (No. 81170244), Beijing Nova Program (No. 2009B39)
and Beijing Natural Science Foundation (No. 7102057).
NR 23
TC 1
Z9 1
U1 0
U2 1
PU CHINESE MEDICAL ASSOC
PI BEIJING
PA 42 DONGSI XIDAJIE, BEIJING 100710, PEOPLES R CHINA
SN 0366-6999
J9 CHINESE MED J-PEKING
JI Chin. Med. J.
PD MAR 20
PY 2014
VL 127
IS 6
BP 1022
EP 1026
DI 10.3760/cma.j.issn.0366-6999.20132954
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA AE9JW
UT WOS:000334325100005
PM 24622428
ER
PT J
AU Vassy, JL
Lautenbach, DM
McLaughlin, HM
Kong, SW
Christensen, KD
Krier, J
Kohane, IS
Feuerman, LZ
Blumenthal-Barby, J
Roberts, JS
Lehmann, LS
Ho, CY
Ubel, PA
MacRae, CA
Seidman, CE
Murray, MF
McGuire, AL
Rehm, HL
Green, RC
AF Vassy, Jason L.
Lautenbach, Denise M.
McLaughlin, Heather M.
Kong, Sek Won
Christensen, Kurt D.
Krier, Joel
Kohane, Isaac S.
Feuerman, Lindsay Z.
Blumenthal-Barby, Jennifer
Roberts, J. Scott
Lehmann, Lisa Soleymani
Ho, Carolyn Y.
Ubel, Peter A.
MacRae, Calum A.
Seidman, Christine E.
Murray, Michael F.
McGuire, Amy L.
Rehm, Heidi L.
Green, Robert C.
CA MedSeq Project
TI The MedSeq Project: a randomized trial of integrating whole genome
sequencing into clinical medicine
SO TRIALS
LA English
DT Article
DE Whole genome sequencing; Genome report; Genomic medicine; Translational
genomics; Primary care; Cardiomyopathy genetics
ID PERSONALIZED MEDICINE; INFORMED-CONSENT; DIAGNOSIS; EXOME; SCALE;
VALIDATION; GENETICIST; STATEMENT; DISEASES; OUTBREAK
AB Background: Whole genome sequencing (WGS) is already being used in certain clinical and research settings, but its impact on patient well-being, health-care utilization, and clinical decision-making remains largely unstudied. It is also unknown how best to communicate sequencing results to physicians and patients to improve health. We describe the design of the MedSeq Project: the first randomized trials of WGS in clinical care.
Methods/Design: This pair of randomized controlled trials compares WGS to standard of care in two clinical contexts: (a) disease-specific genomic medicine in a cardiomyopathy clinic and (b) general genomic medicine in primary care. We are recruiting 8 to 12 cardiologists, 8 to 12 primary care physicians, and approximately 200 of their patients. Patient participants in both the cardiology and primary care trials are randomly assigned to receive a family history assessment with or without WGS. Our laboratory delivers a genome report to physician participants that balances the needs to enhance understandability of genomic information and to convey its complexity. We provide an educational curriculum for physician participants and offer them a hotline to genetics professionals for guidance in interpreting and managing their patients' genome reports. Using varied data sources, including surveys, semi-structured interviews, and review of clinical data, we measure the attitudes, behaviors and outcomes of physician and patient participants at multiple time points before and after the disclosure of these results.
Discussion: The impact of emerging sequencing technologies on patient care is unclear. We have designed a process of interpreting WGS results and delivering them to physicians in a way that anticipates how we envision genomic medicine will evolve in the near future. That is, our WGS report provides clinically relevant information while communicating the complexity and uncertainty of WGS results to physicians and, through physicians, to their patients. This project will not only illuminate the impact of integrating genomic medicine into the clinical care of patients but also inform the design of future studies.
C1 [Vassy, Jason L.] VA Boston Healthcare Syst, Gen Internal Med Sect, Boston, MA 02130 USA.
[Christensen, Kurt D.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02130 USA.
[Vassy, Jason L.; Lautenbach, Denise M.; Christensen, Kurt D.; Krier, Joel; MacRae, Calum A.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
[McLaughlin, Heather M.; Rehm, Heidi L.] Partners Healthcare Ctr Personalized Genet Med, Mol Med Lab, Cambridge, MA 02139 USA.
[McLaughlin, Heather M.; Rehm, Heidi L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[McLaughlin, Heather M.; Rehm, Heidi L.; Green, Robert C.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Kong, Sek Won] Boston Childrens Hosp, Dept Med, Boston, MA 02115 USA.
[Kong, Sek Won; Krier, Joel; Kohane, Isaac S.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Kohane, Isaac S.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA.
[Feuerman, Lindsay Z.; Blumenthal-Barby, Jennifer; McGuire, Amy L.] Baylor Coll Med, BCM Jewish Inst Res, Ctr Med Eth & Hlth Policy, Houston, TX 77030 USA.
[Roberts, J. Scott] Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA.
[Lehmann, Lisa Soleymani] Brigham & Womens Hosp, Dept Med, Div Gen Internal Med & Primary Care, Ctr Bioeth, Boston, MA 02120 USA.
[Lehmann, Lisa Soleymani] Harvard Univ, Sch Med, Boston, MA 02120 USA.
[Ho, Carolyn Y.; MacRae, Calum A.; Seidman, Christine E.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA.
[Ubel, Peter A.] Duke Univ, Fuqua Sch Business, Durham, NC 27708 USA.
[Seidman, Christine E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Murray, Michael F.] Geisinger Hlth Syst, Genom Med Inst, Wilkes Barre, PA 18711 USA.
[Green, Robert C.] Genomes2People, Boston, MA 02115 USA.
[Green, Robert C.] Brigham & Womens Hosp, Div Genet, Dept Med, Boston, MA 02115 USA.
RP Green, RC (reprint author), Genomes2People, 41 Ave Louis Pasteur, Boston, MA 02115 USA.
EM rcgreen@genetics.med.harvard.edu
OI Ho, Carolyn/0000-0002-7334-7924; Christensen, Kurt/0000-0003-4068-776X;
Lebo, Matthew/0000-0002-9733-5207
FU National Institutes of Health (NIH) National Human Genome Research
Institute [U01-HG006500]; NIH [L30 DK089597, F32 HG006993, T32
GM007748-34]; Clinical Translational Science Award [UL1RR025758];
Brigham and Women's Hospital from the National Center for Research
Resources
FX The MedSeq Project is supported by the National Institutes of Health
(NIH) National Human Genome Research Institute (U01-HG006500). JLV is
supported by NIH L30 DK089597. KDC is supported by NIH F32 HG006993. JK
is supported by NIH T32 GM007748-34. The project described was supported
by Clinical Translational Science Award UL1RR025758 to Harvard
University and Brigham and Women's Hospital from the National Center for
Research Resources. The content is solely the responsibility of the
authors and does not necessarily represent the official views of the
National Center for Research Resources or the National Institutes of
Health. The authors thank 5AM Solutions, Inc. (Rockville, MD, USA), for
their help in customizing the workflow of the "My Family Health
Portrait" web tool for this study.
NR 56
TC 43
Z9 44
U1 11
U2 21
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6215
J9 TRIALS
JI Trials
PD MAR 20
PY 2014
VL 15
AR 85
DI 10.1186/1745-6215-15-85
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AF7AX
UT WOS:000334866900001
PM 24645908
ER
PT J
AU Cornejo-Olivas, MR
Yu, CE
Mazzetti, P
Mata, IF
Meza, M
Lindo-Samanamud, S
Leverenz, JB
Bird, TD
AF Cornejo-Olivas, Mario R.
Yu, Chang-En
Mazzetti, Pilar
Mata, Ignacio F.
Meza, Maria
Lindo-Samanamud, Saul
Leverenz, James B.
Bird, Thomas D.
TI Clinical and molecular studies reveal a PSEN1 mutation (L153V) in a
Peruvian family with early-onset Alzheimer's disease
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE Presenilin-1; Peruvian; Early-onset Alzheimer's disease
ID PRECURSOR PROTEIN; PRESENILIN; GENETICS; FREQUENCY; GENES
AB Presenilin 1 (PSEN1) gene mutations are found in 30-70% of familial early-onset Alzheimer disease (EOAD) cases (onset <60 years). Prevalence of these mutations is highly variable including ethnic differences worldwide. No Peruvian kindred with familial AD (FAD) have been described. Standardized clinical evaluation and cognitive assessment were completed in a Peruvian family with severe EOAD. Clinical course was characterized by very early onset (before age 35 years), progressive cognitive impairment with early memory loss, spatial disorientation and executive dysfunction. We sequenced all exons of PSEN1 in the proband and identified a c.475C>G DNA change resulting in a p.L153V missense mutation in the transmembrane domain 2 of the gene. This mutation is also present in the three additional affected siblings but not in a non-affected family member consistent with segregation of this mutation with the disease. This is the first report of a Peruvian family affected with EOAD associated with a PSEN1 mutation. This same mutation has been reported previously in English and French families, but a novel variants very close to the mutation and ancestry informative markers analysis suggests the mutation might be of Amerindian or African origin in this Peruvian family. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
C1 [Cornejo-Olivas, Mario R.; Mazzetti, Pilar; Lindo-Samanamud, Saul] Inst Nacl Ciencias Neurol, Neurogenet Res Ctr, Lima 01, Peru.
[Cornejo-Olivas, Mario R.] Northern Pacific Global Hlth Res Fellows Training, Bethesda, MD USA.
[Mazzetti, Pilar; Meza, Maria] Univ Nacl Mayor San Marcos, Sch Med, Lima 14, Peru.
[Yu, Chang-En; Leverenz, James B.; Bird, Thomas D.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA.
[Leverenz, James B.] VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA.
[Mata, Ignacio F.; Leverenz, James B.; Bird, Thomas D.] VA Puget Sound Hlth Care Syst, Parkinsons Res Educ & Clin Ctr, Seattle, WA USA.
[Mata, Ignacio F.; Leverenz, James B.; Bird, Thomas D.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA.
[Leverenz, James B.; Bird, Thomas D.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
RP Cornejo-Olivas, MR (reprint author), Inst Nacl Ciencias Neurol, Neurogenet Res Ctr, 1271 Ancash St Lima, Lima 01, Peru.
EM mario.cornejo.o@incngen.org.pe
OI Cornejo-Olivas, Mario /0000-0001-6313-5680
FU NIH [R25 TW009345]; Fogarty International Center; National Institute of
Mental Health; NIH Office of the Director Office of Research on Women's
Health; NIH Office of AIDS Research
FX We want to thank the Latin American Research Consortium on the Genetics
of Parkinson's disease (LARGE PD) for providing healthy control samples
from Peru. This project was supported by NIH Research Training Grant #
R25 TW009345 funded by the Fogarty International Center, the National
Institute of Mental Health, and the NIH Office of the Director Office of
Research on Women's Health and the Office of AIDS Research.
NR 18
TC 1
Z9 3
U1 0
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3940
EI 1872-7972
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD MAR 20
PY 2014
VL 563
BP 140
EP 143
DI 10.1016/j.neulet.2014.01.016
PG 4
WC Neurosciences
SC Neurosciences & Neurology
GA AE5CR
UT WOS:000334005900029
PM 24495933
ER
PT J
AU Wang, Y
Godec, J
Ben-Aissa, K
Cui, KR
Zhao, KJ
Pucsek, AB
Lee, YK
Weaver, CT
Yagi, R
Lazarevic, V
AF Wang, Yan
Godec, Jernej
Ben-Aissa, Khadija
Cui, Kairong
Zhao, Keji
Pucsek, Alexandra B.
Lee, Yun Kyung
Weaver, Casey T.
Yagi, Ryoji
Lazarevic, Vanja
TI The Transcription Factors T-bet and Runx Are Required for the Ontogeny
of Pathogenic Interferon-gamma-Producing T Helper 17 Cells
SO IMMUNITY
LA English
DT Article
ID IFNG GENE-EXPRESSION; HUMAN TH17 CELLS; ROR-GAMMA; T(H)17 CELLS;
LINEAGE; DIFFERENTIATION; PLASTICITY; CYTOKINE; FOXP3; ENCEPHALOMYELITIS
AB T helper 17 (Th17) cells can give rise to interleukin-17A (IL-17A)- and interferon (IFN)-gamma-double-producing cells that are implicated in development of autoimmune diseases. However, the molecular mechanisms that govern generation of IFN-gamma-producing Th17 cells are unclear. We found that coexpression of the Th1 and Th17 cell master transcription factors, T-bet and retinoid-related orphan receptor gamma-t (ROR gamma t), respectively, did not generate Th cells with robust IL-17 and IFN-gamma expression. Instead, development of IFN-gamma-producing Th17 cells required T-bet and Runx1 or Runx3. IL-12-stimulated Th17 cells upregulated Runx1, which bound to the Ifng locus in a T-bet-dependent manner. Reciprocally, T-bet or Runx1 deficiency or inhibition of Runx transcriptional activity impaired the development of IFN-gamma-producing Th17 cells during experimental autoimmune encephalomyelitis, which correlated with substantially ameliorated disease course. Thus, our studies identify a critical role for T-bet and Runx transcription factors in the generation of pathogenic IFN-gamma-producing Th17 cells.
C1 [Wang, Yan; Ben-Aissa, Khadija; Lazarevic, Vanja] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Godec, Jernej] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
[Godec, Jernej] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Cui, Kairong; Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Pucsek, Alexandra B.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21231 USA.
[Lee, Yun Kyung; Weaver, Casey T.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA.
[Yagi, Ryoji] Chiba Univ, Grad Sch Med, Dept Immunol, Chiba 2608670, Japan.
RP Lazarevic, V (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM lazarevicv@mail.nih.gov
OI Weaver, Casey/0000-0002-2180-1793
FU Intramural NIH HHS [ZIA BC011431-02]; NCI NIH HHS [P30 CA013148]; NIAMS
NIH HHS [P30 AR048311]; NIDDK NIH HHS [P01 DK071176]
NR 39
TC 46
Z9 46
U1 2
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
EI 1097-4180
J9 IMMUNITY
JI Immunity
PD MAR 20
PY 2014
VL 40
IS 3
BP 355
EP 366
DI 10.1016/j.immuni.2014.01.002
PG 12
WC Immunology
SC Immunology
GA AD7DQ
UT WOS:000333422300009
PM 24530058
ER
PT J
AU Lee, REC
Walker, SR
Savery, K
Frank, DA
Gaudet, S
AF Lee, Robin E. C.
Walker, Sarah R.
Savery, Kate
Frank, David A.
Gaudet, Suzanne
TI Fold Change of Nuclear NF-kappa B Determines TNF-Induced Transcription
in Single Cells
SO MOLECULAR CELL
LA English
DT Article
ID RESPONSE ELEMENTS; GENE-EXPRESSION; ACTIVATION; P50; INFLAMMATION;
SPECIFICITY; MACROPHAGES; VARIABILITY; APOPTOSIS; PROMOTER
AB In response to tumor necrosis factor (TNF), NF-kappa B enters the nucleus and promotes inflammatory and stress-responsive gene transcription. Because NF-kappa B deregulation is associated with disease, one might expect strict control of NF-kappa B localization. However, nuclear NF-kappa B levels exhibit considerable cell-to-cell variability, even in unstimulated cells. To resolve this paradox and determine how transcription-inducing signals are encoded, we quantified single-cell NF-kappa B translocation dynamics and transcription in the same cells. We show that TNF-induced transcription correlates best with fold change in nuclear NF-kappa B, not absolute nuclear NF-kappa B abundance. Using computational modeling, we find that an incoherent feedforward loop, from competition for binding to kappa B motifs, could provide memory of the preligand state necessary for fold-change detection. Experimentally, we observed three gene-specific transcriptional patterns that our model recapitulates by modulating competition strength alone. Fold-change detection buffers against stochastic variation in signaling molecules and explains how cells tolerate variability in NF-kappa B abundance and localization.
C1 [Lee, Robin E. C.; Savery, Kate; Gaudet, Suzanne] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
[Lee, Robin E. C.; Savery, Kate; Gaudet, Suzanne] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02215 USA.
[Lee, Robin E. C.; Gaudet, Suzanne] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Walker, Sarah R.; Frank, David A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Walker, Sarah R.; Frank, David A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Walker, Sarah R.; Frank, David A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
RP Gaudet, S (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
EM suzanne_gaudet@dfci.harvard.edu
FU NIH [CA139980, R01-GM104247]; Barr investigator award; NCI
[R01-CA160979]; DeGregorio Family Foundation
FX We thank B. B. Aldridge, W. W. Chen, M. S. Owen, X. Xia, and A. Aref for
advice on the manuscript and many helpful discussions and L. Hill for
technical assistance. We also thank Dr. Max Heiman for the use of his
microscope. This work was funded by NIH grant CA139980, R01-GM104247 and
a Barr investigator award to S. G., and NCI grant R01-CA160979 and
funding from the DeGregorio Family Foundation to D. A. F. S. G. is a
Kimmel Scholar, and R. E. C. L is a CIHR research fellow.
NR 50
TC 39
Z9 40
U1 0
U2 17
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
EI 1097-4164
J9 MOL CELL
JI Mol. Cell
PD MAR 20
PY 2014
VL 53
IS 6
BP 867
EP 879
DI 10.1016/j.molcel.2014.01.026
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AD5YM
UT WOS:000333329400004
PM 24530305
ER
PT J
AU Manning, AL
Yazinski, SA
Nicolay, B
Bryll, A
Zou, L
Dyson, NJ
AF Manning, Amity L.
Yazinski, Stephanie A.
Nicolay, Brandon
Bryll, Alysia
Zou, Lee
Dyson, Nicholas J.
TI Suppression of Genome Instability in pRB-Deficient Cells by Enhancement
of Chromosome Cohesion
SO MOLECULAR CELL
LA English
DT Article
ID CONDENSIN-II; CLONAL EVOLUTION; DNA-REPLICATION; CONSTITUTIVE
HETEROCHROMATIN; PERICENTRIC HETEROCHROMATIN; RETINOBLASTOMA PROTEIN;
MICROARRAY ANALYSIS; COLORECTAL CANCERS; CYCLE PROGRESSION; RB
AB Chromosome instability (CIN), a common feature of solid tumors, promotes tumor evolution and increases drug resistance during therapy. We previously demonstrated that loss of the retinoblastoma protein (pRB) tumor suppressor causes changes in centromere structure and generates CIN. However, the mechanism and significance of this change was unclear. Here, we show that defects in cohesion are key to the pRB loss phenotype. pRB loss alters H4K20 methylation, a prerequisite for efficient establishment of cohesion at centromeres. Changes in cohesin regulation are evident during S phase, where they compromise replication and increase DNA damage. Ultimately, such changes compromise mitotic fidelity following pRB loss. Remarkably, increasing cohesion suppressed all of these phenotypes and dramatically reduced CIN in cancer cells lacking functional pRB. These data explain how loss of pRB undermines genomic integrity. Given the frequent functional inactivation of pRB in cancer, conditions that increase cohesion may provide a general strategy to suppress CIN.
C1 [Manning, Amity L.; Yazinski, Stephanie A.; Nicolay, Brandon; Bryll, Alysia; Zou, Lee; Dyson, Nicholas J.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
[Manning, Amity L.; Yazinski, Stephanie A.; Nicolay, Brandon; Bryll, Alysia; Zou, Lee; Dyson, Nicholas J.] Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA.
RP Dyson, NJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
EM dyson@helix.mgh.harvard.edu
FU MGH ECOR Tosteson postdoctoral fellowship; Department of Defense
[BC120504]; NIH [CA155202, GM076388]
FX We thank Katsuhiko Shirahige for the generous gift of AcSMC3 antibodies,
Duane Compton for sharing the mCherry Mad2 construct, and Andreas
Heilman for technical support. A. L. M. is supported by an MGH ECOR
Tosteson postdoctoral fellowship; S.A.Y. is supported by a fellowship
from the Department of Defense (BC120504); L.Z. is a Jim and Ann Orr MGH
Research Scholar; and N.J.D. is a James and Shirley Curvey MGH Research
Scholar. This work was supported by NIH grants to N.J.D. (CA155202) and
L.Z. (GM076388).
NR 63
TC 21
Z9 21
U1 1
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
EI 1097-4164
J9 MOL CELL
JI Mol. Cell
PD MAR 20
PY 2014
VL 53
IS 6
BP 993
EP 1004
DI 10.1016/j.molcel.2014.01.032
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AD5YM
UT WOS:000333329400014
PM 24613344
ER
PT J
AU Ducker, GS
Atreya, CE
Simko, JP
Hom, YK
Matli, MR
Benes, CH
Hann, B
Nakakura, EK
Bergsland, EK
Donner, DB
Settleman, J
Shokat, KM
Warren, RS
AF Ducker, G. S.
Atreya, C. E.
Simko, J. P.
Hom, Y. K.
Matli, M. R.
Benes, C. H.
Hann, B.
Nakakura, E. K.
Bergsland, E. K.
Donner, D. B.
Settleman, J.
Shokat, K. M.
Warren, R. S.
TI Incomplete inhibition of phosphorylation of 4E-BP1 as a mechanism of
primary resistance to ATP-competitive mTOR inhibitors
SO ONCOGENE
LA English
DT Article
DE mTOR; colon cancer; PIK3CA; KRAS; xenograft; PP242
ID RENAL-CELL CARCINOMA; COLORECTAL-CANCER; KINASE INHIBITORS; BINDING
PARTNER; PIK3CA MUTATION; GROWTH-CONTROL; COLON-CANCER; LUNG-CANCER;
IN-VITRO; RAPAMYCIN
AB The mammalian target of rapamycin (mTOR) regulates cell growth by integrating nutrient and growth factor signaling and is strongly implicated in cancer. But mTOR is not an oncogene, and which tumors will be resistant or sensitive to new adenosine triphosphate (ATP) competitive mTOR inhibitors now in clinical trials remains unknown. We screened a panel of over 600 human cancer cell lines to identify markers of resistance and sensitivity to the mTOR inhibitor PP242. RAS and phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) mutations were the most significant genetic markers for resistance and sensitivity to PP242, respectively; colon origin was the most significant marker for resistance based on tissue type. Among colon cancer cell lines, those with KRAS mutations were most resistant to PP242, whereas those without KRAS mutations most sensitive. Surprisingly, cell lines with co-mutation of PIK3CA and KRAS had intermediate sensitivity. Immunoblot analysis of the signaling targets downstream of mTOR revealed that the degree of cellular growth inhibition induced by PP242 was correlated with inhibition of phosphorylation of the translational repressor eIF4E-binding protein 1 (4E-BP1), but not ribosomal protein S6 (rpS6). In a tumor growth inhibition trial of PP242 in patient-derived colon cancer xenografts, resistance to PP242-induced inhibition of 4E-BP1 phosphorylation and xenograft growth was again observed in KRAS mutant tumors without PIK3CA co-mutation, compared with KRAS wild-type controls. We show that, in the absence of PIK3CA co-mutation, KRAS mutations are associated with resistance to PP242 and that this is specifically linked to changes in the level of phosphorylation of 4E-BP1.
C1 [Ducker, G. S.; Shokat, K. M.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
[Atreya, C. E.; Bergsland, E. K.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Simko, J. P.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA.
[Hom, Y. K.; Hann, B.] Univ Calif San Francisco, Preclin Therapeut Core, San Francisco, CA 94143 USA.
[Hom, Y. K.; Matli, M. R.; Hann, B.; Nakakura, E. K.; Donner, D. B.; Shokat, K. M.; Warren, R. S.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
[Matli, M. R.; Nakakura, E. K.; Donner, D. B.; Warren, R. S.] Univ Calif San Francisco, Dept Surg, Sect Surg Oncol, San Francisco, CA 94115 USA.
[Benes, C. H.; Settleman, J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA.
[Shokat, K. M.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA USA.
[Shokat, K. M.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA.
RP Shokat, KM (reprint author), Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, 600 E 16th St,MC 2280, San Francisco, CA 94158 USA.
EM shokat@cmp.ucsf.edu; robert.warren@ucsfmedctr.org
OI Ducker, Gregory/0000-0002-8651-6846
FU American Cancer Society Postdoctoral Fellowship [11-183-TBG]; Millennium
Pharmaceuticals provided through the Alliance for Clinical Trials in
Oncology Foundation; Littlefield Trust; Howard Hughes Medical Institute;
Waxman Foundation
FX We thank Dan Moore for his critical assistance in the statistical
analysis, Sandy Devries for FISH analysis, Katherine Pogue-Guile for
permission to use the ColoCarta oligonucleotide primer design files and
Morris Feldman, Jon Ostrem and Iana Serafimova for reagents. CEA is
supported in part by American Cancer Society Postdoctoral Fellowship
11-183-TBG; she also acknowledges support Millennium Pharmaceuticals
provided through the Alliance for Clinical Trials in Oncology
Foundation. RSW is supported in part by a charitable donation from the
Littlefield 2000 Trust. KMS is supported by the Howard Hughes Medical
Institute and the Waxman Foundation.
NR 56
TC 23
Z9 23
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD MAR 20
PY 2014
VL 33
IS 12
BP 1590
EP 1600
DI 10.1038/onc.2013.92
PG 11
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA AD4TS
UT WOS:000333244200012
PM 23542178
ER
PT J
AU Chung, AW
Ghebremichael, M
Robinson, H
Brown, E
Choi, I
Lane, S
Dugast, AS
Schoen, MK
Rolland, M
Suscovich, TJ
Mahan, AE
Liao, L
Streeck, H
Andrews, C
Rerks-Ngarm, S
Nitayaphan, S
de Souza, MS
Kaewkungwal, J
Pitisuttithum, P
Francis, D
Michael, NL
Kim, JH
Bailey-Kellogg, C
Ackerman, ME
Alter, G
AF Chung, Amy W.
Ghebremichael, Musie
Robinson, Hannah
Brown, Eric
Choi, Ickwon
Lane, Sophie
Dugast, Anne-Sophie
Schoen, Matthew K.
Rolland, Morgane
Suscovich, Todd J.
Mahan, Alison E.
Liao, Larry
Streeck, Hendrik
Andrews, Charla
Rerks-Ngarm, Supachai
Nitayaphan, Sorachai
de Souza, Mark S.
Kaewkungwal, Jaranit
Pitisuttithum, Punnee
Francis, Donald
Michael, Nelson L.
Kim, Jerome H.
Bailey-Kellogg, Chris
Ackerman, Margaret E.
Alter, Galit
TI Polyfunctional Fc-Effector Profiles Mediated by IgG Subclass Selection
Distinguish RV144 and VAX003 Vaccines
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID NEUTRALIZING ANTIBODY-RESPONSE; HIV-SPECIFIC ANTIBODIES; B-CELL
RESPONSES; EFFICACY TRIAL; HIV-1-INFECTED INDIVIDUALS;
PLASMODIUM-FALCIPARUM; GLYCOFORM SELECTION; TETANUS VACCINATION;
HIGH-THROUGHPUT; INFECTION
AB The human phase 2B RV144 ALVAC-HIV vCP1521/AIDSVAX B/E vaccine trial, held in Thailand, resulted in an estimated 31.2% efficacy against HIV infection. By contrast, vaccination with VAX003 (consisting of only AIDSVAX B/E) was not protective. Because protection within RV144 was observed in the absence of neutralizing antibody activity or cytotoxic T cell responses, we speculated that the specificity or qualitative differences in Fc-effector profiles of nonneutralizing antibodies may have accounted for the efficacy differences observed between the two trials. We show that the RV144 regimen elicited nonneutralizing antibodies with highly coordinated Fc-mediated effector responses through the selective induction of highly functional immunoglobulin G3 (IgG3). By contrast, VAX003 elicited monofunctional antibody responses influenced by IgG4 selection, which was promoted by repeated AIDSVAX B/E protein boosts. Moreover, only RV144 induced IgG1 and IgG3 antibodies targeting the crown of the HIV envelope V2 loop, albeit with limited coverage of breakthrough viral sequences. These data suggest that subclass selection differences associated with coordinated humoral functional responses targeting strain-specific protective V2 loop epitopes may underlie differences in vaccine efficacy observed between these two vaccine trials.
C1 [Chung, Amy W.; Ghebremichael, Musie; Robinson, Hannah; Lane, Sophie; Dugast, Anne-Sophie; Schoen, Matthew K.; Suscovich, Todd J.; Mahan, Alison E.; Alter, Galit] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA 02139 USA.
[Brown, Eric; Ackerman, Margaret E.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA.
[Choi, Ickwon; Bailey-Kellogg, Chris] Dartmouth Coll, Dept Comp Sci, Hanover, NH 03755 USA.
[Rolland, Morgane; Streeck, Hendrik; Andrews, Charla; Michael, Nelson L.; Kim, Jerome H.] US Mil HIV Res Program, Walter Reed Army Inst Res, Dept Mol Virol & Pathogenesis, Silver Spring, MD 20910 USA.
[Liao, Larry] Duke Univ, Human Vaccine Inst, Durham, NC 27710 USA.
[Liao, Larry] Ctr HIV AIDS Vaccine Immunol, Durham, NC 27710 USA.
[Rerks-Ngarm, Supachai] Minist Publ Hlth, Dept Dis Control, Nonthaburi 11000, Thailand.
[Nitayaphan, Sorachai; de Souza, Mark S.] Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand.
[Kaewkungwal, Jaranit; Pitisuttithum, Punnee] Mahidol Univ, Fac Trop Med, Bangkok 10400, Thailand.
[Francis, Donald] Global Solut Infect Dis, Brisbane, CA 94005 USA.
RP Alter, G (reprint author), Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA 02139 USA.
EM galter@partners.org
RI Dugast, AnneSophie/L-9541-2015
FU US Military HIV Research Program (MHRP); NIH [R01 AI080289]; American
Australian Association (Amgen Fellowship); National Health and Medical
Research Center [APP1036470]; Bill and Melinda Gates Foundation
Collaboration; NIH Harvard Center for AIDS Research [P30 AI060354-02]
FX This work was supported by the US Military HIV Research Program (MHRP)
(A.W.C. and G.A.), NIH (R01 AI080289) (G.A.), American Australian
Association (Amgen Fellowship) (A.W.C.), National Health and Medical
Research Center (APP1036470) (A.W.C.), Bill and Melinda Gates Foundation
Collaboration for AIDS Vaccine Discovery (A.W.C., E.B., I.C., A.-S.D.,
A.E.M., C.B.-K., M.E.A., and G.A.), and NIH Harvard Center for AIDS
Research (P30 AI060354-02) (G.A.).
NR 41
TC 24
Z9 24
U1 3
U2 6
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD MAR 19
PY 2014
VL 6
IS 228
AR 228ra8
PG 11
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA AD4XV
UT WOS:000333256000002
ER
PT J
AU Olfson, M
Marcus, SC
Bridge, JA
AF Olfson, Mark
Marcus, Steven C.
Bridge, Jeffrey A.
TI Focusing Suicide Prevention on Periods of High Risk
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID DELIBERATE SELF-HARM; CARE
C1 [Olfson, Mark] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA.
[Olfson, Mark] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Marcus, Steven C.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
[Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA.
[Bridge, Jeffrey A.] Nationwide Childrens Hosp, Res Inst, Ctr Innovat Pediat Practice, Columbus, OH USA.
[Bridge, Jeffrey A.] Ohio State Univ, Columbus, OH 43210 USA.
RP Olfson, M (reprint author), Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York State Psychiat Inst, 1051 Riverside Dr, New York, NY 10032 USA.
EM mo49@columbia.edu
FU AHRQ HHS [U19 HS021112]
NR 10
TC 27
Z9 28
U1 2
U2 7
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAR 19
PY 2014
VL 311
IS 11
BP 1107
EP 1108
DI 10.1001/jama.2014.501
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA AD1RC
UT WOS:000333010100011
PM 24515285
ER
PT J
AU Hayes, JH
Barry, MJ
AF Hayes, Julia H.
Barry, Michael J.
TI Screening for Prostate Cancer With the Prostate-Specific Antigen Test A
Review of Current Evidence
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Review
ID RANDOMIZED CONTROLLED-TRIAL; SERVICES TASK-FORCE; FOLLOW-UP; RADICAL
PROSTATECTOMY; MORTALITY; MEN; STATEMENT; OUTCOMES; RISK; RECOMMENDATION
AB IMPORTANCE Prostate cancer screening with the prostate-specific antigen (PSA) test remains controversial.
OBJECTIVE To review evidence from randomized trials and related modeling studies examining the effect of PSA screening vs no screening on prostate cancer-specific mortality and to suggest an approach balancing potential benefits and harms.
EVIDENCE ACQUISITION MEDLINE, EMBASE, and the Cochrane Register of Controlled Trials were searched from January 1, 2010, to April 3, 2013, for PSA screening trials to update a previous systematic review. Another search was performed in EMBASE and MEDLINE to identify modeling studies extending the results of the 2 large randomized trials identified. The American Heart Association Evidence-Based Scoring System was used to rate level of evidence.
RESULTS Two trials-the Prostate, Lung, Colorectal and Ovarian (PLCO) screening trial and the European Randomized Study of Screening for Prostate Cancer (ERSPC)-dominate the evidence regarding PSA screening. The former trial demonstrated an increase in cancer incidence in the screening group (relative risk [RR], 1.12; 95% CI, 1.07-1.17) but no cancer-specific mortality benefit to PSA screening after 13-year follow-up (RR, 1.09; 95% CI, 0.87-1.36). The ERSPC demonstrated an increase in cancer incidence with screening (RR, 1.63; 95% CI, 1.57-1.69) and an improvement in the risk of prostate cancer-specific death after 11 years (RR, 0.79; 95% CI, 0.68-0.91). The ERSPC documented that 37 additional men needed to receive a diagnosis through screening for every 1 fewer prostate cancer death after 11 years of follow-up among men aged 55 to 69 years (level B evidence for prostate cancer mortality reduction). Harms associated with screening include false-positive results and complications of biopsy and treatment. Modeling studies suggest that this high ratio of additional men receiving diagnoses to prostate cancer deaths prevented will decrease during a longer follow-up (level B evidence).
CONCLUSIONS AND RELEVANCE Available evidence favors clinician discussion of the pros and cons of PSA screening with average-risk men aged 55 to 69 years. Only men who express a definite preference for screening should have PSA testing. Other strategies to mitigate the potential harms of screening include considering biennial screening, a higher PSA threshold for biopsy, and conservative therapy for men receiving a new diagnosis of prostate cancer.
C1 [Hayes, Julia H.] Harvard Univ, Sch Med, Inst Canc, Boston, MA USA.
[Hayes, Julia H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA.
[Barry, Michael J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Internal Med, Boston, MA USA.
RP Hayes, JH (reprint author), 450 Brookline Ave,Dana 1230, Boston, MA 02115 USA.
EM julia_hayes@dfci.harvard.edu
NR 54
TC 75
Z9 75
U1 5
U2 40
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAR 19
PY 2014
VL 311
IS 11
BP 1143
EP 1149
DI 10.1001/jama.2014.2085
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA AD1RC
UT WOS:000333010100019
PM 24643604
ER
PT J
AU Holt, DJ
Cassidy, BS
Yue, XM
Rauch, SL
Boeke, EA
Nasr, S
Tootell, RBH
Coombs, G
AF Holt, Daphne J.
Cassidy, Brittany S.
Yue, Xiaomin
Rauch, Scott L.
Boeke, Emily A.
Nasr, Shahin
Tootell, Roger B. H.
Coombs, Garth, III
TI Neural Correlates of Personal Space Intrusion
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE connectivity; fMRI; intraparietal sulcus; personal space; premotor
cortex; social behavior
ID VENTRAL INTRAPARIETAL AREA; INTRINSIC FUNCTIONAL CONNECTIVITY; HUMAN
CEREBRAL-CORTEX; SOCIAL NETWORK SIZE; PREMOTOR CORTEX; INTERPERSONAL
DISTANCE; DEPENDENT PLASTICITY; RESPONSE PROPERTIES; PERIPERSONAL SPACE;
HUMAN BRAIN
AB A parietal-frontal network in primates is thought to support many behaviors occurring in the space around the body, including interpersonal interactions and maintenance of a particular "comfort zone" or distance from other people ("personal space"). To better understand this network in humans, we used functionalMRIto measure the responses to moving objects (faces, cars, simple spheres) and the functional connectivity of two regions in this network, the dorsal intraparietal sulcus (DIPS) and the ventral premotor cortex (PMv). We found that both areas responded more strongly to faces that were moving toward (vs away from) subjects, but did not show this bias in response to comparable motion in control stimuli (cars or spheres). Moreover, these two regions were functionally interconnected. Tests of activity-behavior associations revealed that the strength of DIPS-PMv connectivity was correlated with the preferred distance that subjects chose to stand from an unfamiliar person (personal space size). In addition, the magnitude of DIPS and PMv responses was correlated with the preferred level of social activity. Together, these findings suggest that this parietal-frontal network plays a role in everyday interactions with others.
C1 [Holt, Daphne J.; Boeke, Emily A.; Coombs, Garth, III] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Holt, Daphne J.; Rauch, Scott L.; Tootell, Roger B. H.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Holt, Daphne J.; Boeke, Emily A.; Nasr, Shahin; Tootell, Roger B. H.; Coombs, Garth, III] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Cassidy, Brittany S.] Brandeis Univ, Dept Psychol, Waltham, MA 02453 USA.
[Yue, Xiaomin] NIMH, Bethesda, MD 20892 USA.
[Rauch, Scott L.] McLean Hosp, Belmont, MA 02478 USA.
[Nasr, Shahin; Tootell, Roger B. H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Holt, DJ (reprint author), 149 13th St, Charlestown, MA 02129 USA.
EM dholt@partners.org
FU National Institute of Mental Health [K23MH076054]
FX This study was supported by the National Institute of Mental Health
K23MH076054 (DH).
NR 50
TC 15
Z9 15
U1 2
U2 16
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAR 19
PY 2014
VL 34
IS 12
BP 4123
EP 4134
DI 10.1523/JNEUROSCI.0686-13.2014
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA AD4WX
UT WOS:000333253300002
PM 24647934
ER
PT J
AU Sperling, RA
Rentz, DM
Johnson, KA
Karlawish, J
Donohue, M
Salmon, DP
Aisen, P
AF Sperling, Reisa A.
Rentz, Dorene M.
Johnson, Keith A.
Karlawish, Jason
Donohue, Michael
Salmon, David P.
Aisen, Paul
TI The A4 Study: Stopping AD Before Symptoms Begin?
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Editorial Material
ID PRECLINICAL ALZHEIMERS-DISEASE; RISK
AB A new secondary prevention trial in older people with amyloid accumulation at high risk for Alzheimer's disease dementia should provide insights into whether anti-amyloid therapy can delay cognitive decline.
C1 [Sperling, Reisa A.; Rentz, Dorene M.; Johnson, Keith A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Alzheimer Res & Treatment,Dept Neurol, Boston, MA 02115 USA.
[Sperling, Reisa A.; Rentz, Dorene M.; Johnson, Keith A.] Harvard Aging Brain Study, Dept Neurol, Boston, MA 02114 USA.
[Johnson, Keith A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Karlawish, Jason] Univ Penn, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA.
[Donohue, Michael; Salmon, David P.; Aisen, Paul] Univ Calif San Diego, Alzheimer Dis Cooperat Study, La Jolla, CA 92093 USA.
RP Sperling, RA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Alzheimer Res & Treatment,Dept Neurol, Boston, MA 02115 USA.
EM reisa@rics.bwh.harvard.edu
FU NIA NIH HHS [K24 AG035007, P30 AG010124, U19 AG010483]
NR 10
TC 93
Z9 94
U1 3
U2 12
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD MAR 19
PY 2014
VL 6
IS 228
AR 228fs13
DI 10.1126/scitranslmed.3007941
PG 3
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA AD4XV
UT WOS:000333256000006
PM 24648338
ER
PT J
AU Qi, QB
Chu, AY
Kang, JH
Huang, JY
Rose, LM
Jensen, MK
Liang, LM
Curhan, GC
Pasquale, LR
Wiggs, JL
De Vivo, I
Chan, AT
Choi, HK
Tamimi, RM
Ridker, PM
Hunter, DJ
Willett, WC
Rimm, EB
Chasman, DI
Hu, FB
Qi, L
AF Qi, Qibin
Chu, Audrey Y.
Kang, Jae H.
Huang, Jinyan
Rose, Lynda M.
Jensen, Majken K.
Liang, Liming
Curhan, Gary C.
Pasquale, Louis R.
Wiggs, Janey L.
De Vivo, Immaculata
Chan, Andrew T.
Choi, Hyon K.
Tamimi, Rulla M.
Ridker, Paul M.
Hunter, David J.
Willett, Walter C.
Rimm, Eric B.
Chasman, Daniel I.
Hu, Frank B.
Qi, Lu
TI Fried food consumption, genetic risk, and body mass index: gene-diet
interaction analysis in three US cohort studies
SO BMJ-BRITISH MEDICAL JOURNAL
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; FREQUENCY QUESTIONNAIRE; PHYSICAL-ACTIVITY;
ENVIRONMENT INTERACTION; ALCOHOL-CONSUMPTION; BREAST-CANCER; OBESITY;
WOMEN; REPRODUCIBILITY; VALIDITY
AB Objective To examine the interactions between genetic predisposition and consumption of fried food in relation to body mass index (BMI) and obesity.
Design Prospective cohort study.
Setting Health professionals in the United States.
Participants 9623 women from the Nurses' Health Study, 6379 men from the Health Professionals Follow-up Study, and a replication cohort of 21 421 women from the Women's Genome Health Study.
Main outcome measure Repeated measurement of BMI over follow-up.
Results There was an interaction between fried food consumption and a genetic risk score based on 32 BMI-associated variants on BMI in both the Nurses' Health Study and Health Professionals Follow-up Study (P <= 0.001 for interaction). Among participants in the highest third of the genetic risk score, the differences in BMI between individuals who consumed fried foods four or more times a week and those who consumed fried foods less than once a week amounted to 1.0 (SE 0.2) in women and 0.7 (SE 0.2) in men, whereas the corresponding differences were 0.5 (SE 0.2) and 0.4 (SE 0.2) in the lowest third of the genetic risk score. The gene-diet interaction was replicated in the Women's Genome Health Study (P<0.001 for interaction). Viewed differently, the genetic association with adiposity was strengthened with higher consumption of fried foods. In the combined three cohorts, the differences in BMI per 10 risk alleles were 1.1 (SE 0.2), 1.6 (SE 0.3), and 2.2 (SE 0.6) for fried food consumption less than once, one to three times, and four or more times a week (P<0.001 for interaction); and the odds ratios (95% confidence intervals) for obesity per 10 risk alleles were 1.61 (1.40 to 1.87), 2.12 (1.73 to 2.59), and 2.72 (2.12 to 3.48) across the three categories of consumption (P=0.002 for interaction). In addition, the variants in or near genes highly expressed or known to act in the central nervous system showed significant interactions with fried food consumption, with the FTO (fat mass and obesity associated) variant showing the strongest result (P<0.001 for interaction).
Conclusion Our findings suggest that consumption of fried food could interact with genetic background in relation to obesity, highlighting the particular importance of reducing fried food consumption in individuals genetically predisposed to obesity.
C1 [Qi, Qibin; Jensen, Majken K.; Hunter, David J.; Willett, Walter C.; Rimm, Eric B.; Hu, Frank B.; Qi, Lu] Harvard Univ, Dept Nutr, Sch Publ Hlth, Boston, MA 02115 USA.
[Qi, Qibin] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Chu, Audrey Y.; Rose, Lynda M.; Ridker, Paul M.; Chasman, Daniel I.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA.
[Chu, Audrey Y.; Kang, Jae H.; Rose, Lynda M.; Curhan, Gary C.; Pasquale, Louis R.; De Vivo, Immaculata; Chan, Andrew T.; Choi, Hyon K.; Tamimi, Rulla M.; Ridker, Paul M.; Hunter, David J.; Willett, Walter C.; Rimm, Eric B.; Chasman, Daniel I.; Hu, Frank B.; Qi, Lu] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Kang, Jae H.; Curhan, Gary C.; Pasquale, Louis R.; De Vivo, Immaculata; Chan, Andrew T.; Choi, Hyon K.; Tamimi, Rulla M.; Hunter, David J.; Willett, Walter C.; Rimm, Eric B.; Hu, Frank B.; Qi, Lu] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Huang, Jinyan; Liang, Liming; Curhan, Gary C.; De Vivo, Immaculata; Tamimi, Rulla M.; Hunter, David J.; Willett, Walter C.; Rimm, Eric B.; Hu, Frank B.] Harvard Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02115 USA.
[Pasquale, Louis R.; Wiggs, Janey L.] Harvard Univ, Dept Ophthalmol, Sch Med, Mass Eye & Ear Infirm, Boston, MA 02115 USA.
[Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Choi, Hyon K.] Boston Univ, Sch Med, Sect Rheumatol, Boston, MA 02118 USA.
[Choi, Hyon K.] Boston Univ, Sch Med, Clin Epidemiol Unit, Boston, MA 02118 USA.
[Ridker, Paul M.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Dis, Boston, MA 02115 USA.
[Chasman, Daniel I.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
RP Qi, L (reprint author), Harvard Univ, Dept Nutr, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA.
EM nhlqi@channing.harvard.edu
FU National Institutes of Health [DK091718, HL071981, HL073168, CA87969,
CA49449, CA055075, HL34594, HL088521, U01HG004399, DK080140, P30DK46200,
U01CA137088, U54CA155626, DK58845, DK098311, U01HG004728, EY015473,
CA134958, DK70756, DK46200, HL043851, HL080467, CA047988]; Merck
Research Laboratories, North Wales, PA; Amgen; American Heart
Association Scientist Development Award [0730094N]; Arthur Ashley
Williams Foundation; Harvard Ophthalmology Scholar Award (Harvard
Medical School) from the Harvard Glaucoma Center of Excellence
FX This study was supported by grants DK091718, HL071981, HL073168,
CA87969, CA49449, CA055075, HL34594, HL088521, U01HG004399, DK080140,
P30DK46200, U01CA137088, U54CA155626, DK58845, DK098311, U01HG004728,
EY015473, CA134958, DK70756 and DK46200 from the National Institutes of
Health, with additional support for genotyping from Merck Research
Laboratories, North Wales, PA. The Women's Genome Health Study is
supported by HL043851, HL080467 and CA047988 from the National
Institutes of Health, with collaborative scientific support and funding
for genotyping provided by Amgen. LQ is a recipient of the American
Heart Association Scientist Development Award (0730094N). LRP is
supported by the Arthur Ashley Williams Foundation and a Harvard
Ophthalmology Scholar Award (Harvard Medical School) from the Harvard
Glaucoma Center of Excellence. ATC is a Damon Runyon Cancer Foundation
Clinical Investigator. The funding sources had no role in the design or
conduct of the study; collection, management, analysis, and
interpretation of the data; or preparation, review, or approval of the
manuscript.
NR 56
TC 45
Z9 45
U1 1
U2 21
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1756-1833
J9 BMJ-BRIT MED J
JI BMJ-British Medical Journal
PD MAR 19
PY 2014
VL 348
AR g1610
DI 10.1136/bmj.g1610
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA AD7AZ
UT WOS:000333414500002
PM 24646652
ER
PT J
AU Helmerhorst, GTT
Vranceanu, AM
Vrahas, M
Smith, M
Ring, D
AF Helmerhorst, Gijs T. T.
Vranceanu, Ana-Maria
Vrahas, Mark
Smith, Malcolm
Ring, David
TI Risk Factors for Continued Opioid Use One to Two Months After Surgery
for Musculoskeletal Trauma
SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME
LA English
DT Article
ID CHRONIC NONCANCER PAIN; LOW-BACK-PAIN; OPERATIVE TREATMENT;
POSTOPERATIVE PAIN; UNITED-STATES; PRESCRIPTION; ASSOCIATION;
MANAGEMENT; DEPENDENCE; ABUSE
AB Background: The aim of this study was to determine factors associated with self-reported ongoing use of opioid medication one to two months after operative treatment of musculoskeletal trauma.
Methods: Operatively treated patients (n = 145) with musculoskeletal trauma were evaluated one to two months after surgery. Patients indicated if they were taking opioid pain medication and completed several psychological questionnaires: the Center for Epidemiologic Studies Depression Scale, the Pain Catastrophizing Scale, the Pain Anxiety Symptoms Scale, and the Posttraumatic Stress Disorder Checklist, civilian version. The Numeric Rating Scale was used to measure pain intensity. Disability was measured with use of the Short Musculoskeletal Function Assessment Questionnaire and injury severity was measured with use of the Abbreviated Injury Scale.
Results: Patients who scored higher on the catastrophic thinking, anxiety, posttraumatic stress disorder, and depression questionnaires were significantly more likely (p < 0.001) to report taking opioid pain medications one to two months after surgery, regardless of injury severity, fracture site, or treating surgeon. The magnitude of disability as measured by the Short Musculoskeletal Function Assessment score was significantly higher (p < 0.001) in the patients who reported using opioids (40 points) compared with those who reported not using opioids (24 points). A logistic regression model not including pain intensity found that the single best predictor of reported opioid use was catastrophic thinking (odds ratio, 1.12 [95% confidence interval, 1.07 to 1.18]), which explained 23% of the variance (p < 0.001).
Conclusions: Patients who continue to use opioid pain medication one to two months after surgery for musculoskeletal trauma have more psychological distress, less effective coping strategies, and greater symptoms and disability than patients who do not take opioids, irrespective of injury, surgical procedure, or surgeon.
C1 [Helmerhorst, Gijs T. T.; Vranceanu, Ana-Maria; Vrahas, Mark; Smith, Malcolm; Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA.
RP Helmerhorst, GTT (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, 55 Fruit St, Boston, MA 02114 USA.
EM ghelmerhorst@gmail.com; avranceanu@partners.org; mvrahas@partners.org;
rmsmith1@partners.org; dring@partners.org
NR 44
TC 29
Z9 29
U1 1
U2 8
PU JOURNAL BONE JOINT SURGERY INC
PI NEEDHAM
PA 20 PICKERING ST, NEEDHAM, MA 02192 USA
SN 0021-9355
EI 1535-1386
J9 J BONE JOINT SURG AM
JI J. Bone Joint Surg.-Am. Vol.
PD MAR 19
PY 2014
VL 96A
IS 6
BP 495
EP 499
DI 10.2106/JBJS.L.01406
PG 5
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA AD2NP
UT WOS:000333072700009
PM 24647506
ER
PT J
AU Takeuchi, K
Yanai, R
Kumase, F
Morizane, Y
Suzuki, J
Kayama, M
Brodowska, K
Nakazawa, M
Miller, JW
Connor, KM
Vavvas, DG
AF Takeuchi, Kimio
Yanai, Ryoji
Kumase, Fumiaki
Morizane, Yuki
Suzuki, Jun
Kayama, Maki
Brodowska, Katarzyna
Nakazawa, Mitsuru
Miller, Joan W.
Connor, Kip M.
Vavvas, Demetrios G.
TI EGF-Like-Domain-7 Is Required for VEGF-Induced Akt/ERK Activation and
Vascular Tube Formation in an Ex Vivo Angiogenesis Assay
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MICRORNA MIR-126; EGFL7; MECHANISMS; CELLS;
NOTCH; NEUROPILIN-1; RETINOPATHY; INTEGRITY; MIGRATION
AB EGFL7 is a secreted angiogenic factor, which in contrast to the well-known secreted angiogenic molecules VEGF and FGF-2, is almost exclusively expressed by endothelial cells and may act in an autocrine fashion. Prior studies have shown EGFL7 to mediate its angiogenic effects by interfering with the Notch pathway and/or via the intronic miR126. Less is known about its effects on VEGF signaling. We wanted to investigate the role of epidermal growth factor-like domain 7 (EGFL7) in VEGF-driven angiogenesis using an ex vivo Matrigel-embedded mouse eye cup assay and siRNA mediated knockdown of EGFL7 by siRNA. Our results suggested that VEGF-induced vascular tube formation was significantly impaired after siRNA downregulation of EGFL7. In addition, knockdown of EGFL7 suppressed VEGF upregulation of phospho-Akt and phospho-Erk(1/2) in endothelial cells, but did not alter VEGFR phosphorylation and neuropilin-1 protein expression or miR126 expression. Thus, in conclusion, EGFL7 is required for VEGF upregulation of the Akt/Erk (1/2) pathway during angiogenesis, and may represent a new therapeutic target in diseases of pathological neovascularization.
C1 [Takeuchi, Kimio; Yanai, Ryoji; Kumase, Fumiaki; Morizane, Yuki; Suzuki, Jun; Kayama, Maki; Brodowska, Katarzyna; Miller, Joan W.; Connor, Kip M.; Vavvas, Demetrios G.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Angiogenesis Lab,Dept Ophthalmol, Boston, MA 02114 USA.
[Kumase, Fumiaki; Morizane, Yuki] Okayama Univ, Dept Ophthalmol, Grad Sch Med Dent & Pharmaceut Sci, Okayama, Japan.
[Takeuchi, Kimio; Nakazawa, Mitsuru] Hirosaki Univ, Grad Sch Med, Dept Ophthalmol, Aomori, Japan.
RP Vavvas, DG (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Angiogenesis Lab,Dept Ophthalmol, Boston, MA 02114 USA.
EM vavvas@meei.harvard.edu
OI Nakazawa, Mitsuru/0000-0001-6095-5712; Connor, Kip/0000-0002-2048-9080;
Vavvas, Demetrios/0000-0002-8622-6478
FU Research to Prevent Blindness Physician Scientist Award; NIH NEI
[R21EY023079-01A1]; Foundation Lions Eye Research Fund; Yeatts Family
Foundation; Macula Society Research Grant award; Research to Prevent
Blindness Foundation; National Institutes of Health Grant [EY014104,
R01EY022084-01/S1]; Fight for Sight Grant in Aid; Bausch and Lomb Japan
Vitreoretinal fellowship
FX This work was supported, in whole or in part, by Research to Prevent
Blindness Physician Scientist Award (DGV), NIH NEI R21EY023079-01A1
(DGV), Foundation Lions Eye Research Fund (DGV), The Yeatts Family
Foundation (JWM, DGV), 2013 Macula Society Research Grant award (DGV),
unrestricted grant to Massachusetts Eye and Ear Infirmary from the
Research to Prevent Blindness Foundation (to D. G. V. and J.W.M.),
National Institutes of Health Grant EY014104 core grant and
R01EY022084-01/S1 (KMC), the Fight for Sight Grant in Aid (DGV), and a
Bausch and Lomb Japan Vitreoretinal fellowship (KT, YM, JS, and MK). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 33
TC 8
Z9 8
U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 19
PY 2014
VL 9
IS 3
AR e91849
DI 10.1371/journal.pone.0091849
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD6ER
UT WOS:000333348500056
PM 24647208
ER
PT J
AU Kuo, P
Hartzell, TL
Eberlin, KR
Miao, D
Zurakowski, D
Winograd, JM
Day, CS
AF Kuo, Phoebe
Hartzell, Tristan L.
Eberlin, Kyle R.
Miao, Diana
Zurakowski, David
Winograd, Jonathan M.
Day, Charles S.
TI The Characteristics of Referring Facilities and Transferred Hand Surgery
Patients
SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME
LA English
DT Article
ID ON-CALL COVERAGE; CALIFORNIA; LEVEL; TRANSPLANTATION; COMPLICATIONS
AB Background: As emergency departments (EDs) become increasingly overwhelmed and specialist coverage in some EDs decreases, patients may be transferred to tertiary or quaternary facilities for specialized care to decrease patient load at transferring facilities. Our objective was to determine whether facilities that transferred patients for hand surgery had hand surgery coverage and to evaluate any nonmedical factors that might have been associated with transfer.
Methods: A retrospective review was conducted for 1167 visits of hand and wrist patients seen in the EDs of two urban level-I trauma centers. The hand surgery capacity of referring facilities was determined by phone calls to the EDs. Univariate and multivariable analyses were conducted to identify nonmedical factors that could potentially affect the decision to transfer.
Results: A total of 155 (13.3%) of 1167 patients arrived from other facilities for specialized hand care. These patients were significantly more likely to be male (p = 0.02), have noncommercial insurance (p = 0.04), require an interpreter (p = 0.01), and arrive between 6: 00 P.M. and midnight (p = 0.03). In a multivariable analysis, sex and insurance status were significantly associated with transfer (p < 0.05). The subset of ninety-five patients who were transferred from other EDs was significantly more likely to be male (p < 0.01) and arrive on weekends (p < 0.01) or between 6: 00 P.M. and midnight (p < 0.01). Of these patients, seventy-seven (81%) were transferred from an ED that reported partial or full hand surgery coverage. However, only eight (10.4%) received a hand surgery evaluation prior to transfer.
Conclusions: The low percentage of patients receiving hand surgery evaluations prior to transfer suggests that referring hospitals are not using their own hand surgeon resources. Nonmedical factors, including noncommercial insurance and off-hour time of initial arrival, may be associated with the decision to transfer patients.
C1 [Kuo, Phoebe; Miao, Diana; Day, Charles S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Orthoped Surg, Boston, MA 02215 USA.
[Hartzell, Tristan L.] Faith Reg Hlth Serv, Norfolk, NE 68701 USA.
[Eberlin, Kyle R.; Winograd, Jonathan M.] Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, WACC, Boston, MA 02114 USA.
[Zurakowski, David] Childrens Hosp Boston, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA.
RP Kuo, P (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Orthoped Surg, 330 Brookline Ave,Stoneman 10, Boston, MA 02215 USA.
EM cday1@bidmc.harvard.edu
NR 15
TC 4
Z9 4
U1 0
U2 0
PU JOURNAL BONE JOINT SURGERY INC
PI NEEDHAM
PA 20 PICKERING ST, NEEDHAM, MA 02192 USA
SN 0021-9355
EI 1535-1386
J9 J BONE JOINT SURG AM
JI J. Bone Joint Surg.-Am. Vol.
PD MAR 19
PY 2014
VL 96A
IS 6
DI 10.2106/JBJS.L.01213
PG 8
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA CF1QF
UT WOS:000352322000005
PM 24647515
ER
PT J
AU Stengel, A
Tache, Y
AF Stengel, Andreas
Tache, Yvette
TI CRF and urocortin peptides as modulators of energy balance and feeding
behavior during stress
SO FRONTIERS IN NEUROSCIENCE
LA English
DT Review
DE body weight; CRF; food intake; stress; urocortin
ID CORTICOTROPIN-RELEASING-FACTOR; CONDITIONED TASTE-AVERSION;
FACTOR-RECEPTOR EXPRESSION; ENTERIC NERVOUS-SYSTEM; FASTED PLASMA
GHRELIN; REDUCES FOOD-INTAKE; C-FOS EXPRESSION; RAT-BRAIN; INDUCED
ANOREXIA; SIGNALING PATHWAYS
AB Early on, corticotropin-releasing factor (CRF), a hallmark brain peptide mediating many components of the stress response, was shown to affect food intake inducing a robust anorexigenic response when injected into the rodent brain. Subsequently, other members of the CRF signaling family have been identified, namely urocortin (Ucn) 1, Ucn 2, and Ucn 3 which were also shown to decrease food intake upon central or peripheral injection. However, the kinetics of feeding suppression was different with an early decrease following intracerebroventricular injection of CRF and a delayed action of Ucns contrasting with the early onset after systemic injection. CRF and Ucns bind to two distinct G-protein coupled membrane receptors, the CRF1 and CRF2. New pharmacological tools such as highly selective peptide CRF1 or CRF2 agonists or antagonists along with genetic knock-in or knock-out models have allowed delineating the primary role of CRF2 involved in the anorexic response to exogenous administration of CRF and Ucns. Several stressors trigger behavioral changes including suppression of feeding behavior which are mediated by brain CRF receptor activation. The present review will highlight the state-of-knowledge on the effects and mechanisms of action of CRF/Ucns-CRF112 signaling under basal conditions and the role in the alterations of food intake in response to stress.
C1 [Stengel, Andreas] Charite, Charite Ctr Internal Med & Dermatol, Div Gen Internal & Psychosomat Med, D-12200 Berlin, Germany.
[Tache, Yvette] Univ Calif Los Angeles, Dept Med, CURE Digest Dis Res Ctr, Ctr Neurobiol Stress & Womens Hlth,Digest Dis Div, Los Angeles, CA 90024 USA.
[Tache, Yvette] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA.
RP Stengel, A (reprint author), Charite, Charite Ctr Internal Med & Dermatol, Div Gen Internal & Psychosomat Med, Campus Benjamin Franklin,Hindenburgdamm 30, D-12200 Berlin, Germany.
EM andreas.stengel@charite.de; ytache@mednet.ucla.edu
FU NIH (Animal Core) [RO1 DK-33061, DK-41301]; VA Research Career Scientist
(Yvette Tache), German Research Foundation STE [1765/3-1]; Charite
University Funding UFF [89-441176]
FX This work was supported by NIH RO1 DK-33061, NIH Center Grant DK-41301
(Animal Core), VA Research Career Scientist (Yvette Tache), German
Research Foundation STE 1765/3-1 (Andreas Stengel) and Charite
University Funding UFF 89-441176 (Andreas Stengel).
NR 154
TC 21
Z9 22
U1 4
U2 13
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-453X
J9 FRONT NEUROSCI-SWITZ
JI Front. Neurosci.
PD MAR 18
PY 2014
VL 8
AR 52
DI 10.3389/fnins.2014.00052
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA AW7HO
UT WOS:000346435500003
PM 24672423
ER
PT J
AU Lo Re, V
Kallan, MJ
Tate, JP
Localio, AR
Lim, JK
Goetz, MB
Klein, MB
Rimland, D
Rodriguez-Barradas, MC
Butt, AA
Gibert, CL
Brown, ST
Park, L
Dubrow, R
Reddy, KR
Kostman, JR
Strom, BL
Justice, AC
AF Lo Re, Vincent, III
Kallan, Michael J.
Tate, Janet P.
Localio, A. Russell
Lim, Joseph K.
Goetz, Matthew Bidwell
Klein, Marina B.
Rimland, David
Rodriguez-Barradas, Maria C.
Butt, Adeel A.
Gibert, Cynthia L.
Brown, Sheldon T.
Park, Lesley
Dubrow, Robert
Reddy, K. Rajender
Kostman, Jay R.
Strom, Brian L.
Justice, Amy C.
TI Hepatic Decompensation in Antiretroviral-Treated Patients Co-Infected
With HIV and Hepatitis C Virus Compared With Hepatitis C
Virus-Monoinfected Patients A Cohort Study
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHRONIC LIVER-DISEASE; POLYMERASE
CHAIN-REACTION; SIMPLE NONINVASIVE INDEX; VETERANS AGING COHORT;
PROTEIN-S DEFICIENCY; SOCIETY-USA PANEL; FIBROSIS PROGRESSION;
HEPATOCELLULAR-CARCINOMA; HIV/HCV COINFECTION
AB Background: The incidence and determinants of hepatic decompensation have been incompletely examined among patients co-infected with HIV and hepatitis C virus (HCV) in the antiretroviral therapy (ART) era, and few studies have compared outcome rates with those of patients with chronic HCV alone.
Objective: To compare the incidence of hepatic decompensation between antiretroviral-treated patients co-infected with HIV and HCV and HCV-monoinfected patients and to evaluate factors associated with decompensation among co-infected patients receiving ART.
Design: Retrospective cohort study.
Setting: Veterans Health Administration.
Patients: 4280 co-infected patients who initiated ART and 6079 HCV-monoinfected patients receiving care between 1997 and 2010. All patients had detectable HCV RNA and were HCV treatment-naive.
Measurements: Incident hepatic decompensation, determined by diagnoses of ascites, spontaneous bacterial peritonitis, or esophageal variceal hemorrhage.
Results: The incidence of hepatic decompensation was greater among co-infected than monoinfected patients (7.4% vs. 4.8% at 10 years; P < 0.001). Compared with HCV-monoinfected patients, co-infected patients had a higher rate of hepatic decompensation (hazard ratio [HR] accounting for competing risks, 1.56 [95% CI, 1.31 to 1.86]). Co-infected patients who maintained HIV RNA levels less than 1000 copies/mL still had higher rates of decompensation than HCV-monoinfected patients (HR, 1.44 [CI, 1.05 to 1.99]). Baseline advanced hepatic fibrosis (FIB-4 score >3.25) (HR, 5.45 [CI, 3.79 to 7.84]), baseline hemoglobin level less than 100 g/L (HR, 2.24 [CI, 1.20 to 4.20]), diabetes mellitus (HR, 1.88 [CI, 1.38 to 2.56]), and nonblack race (HR, 2.12 [CI, 1.65 to 2.72]) were each associated with higher rates of decompensation among co-infected patients.
Limitation: Observational study of predominantly male patients.
Conclusion: Despite receiving ART, patients co-infected with HIV and HCV had higher rates of hepatic decompensation than HCV-monoinfected patients. Rates of decompensation were higher for co-infected patients with advanced liver fibrosis, severe anemia, diabetes, and nonblack race.
C1 Univ Penn, Philadelphia, PA 19104 USA.
Philadelphia VA Med Ctr, Philadelphia, PA USA.
VA Connecticut Healthcare Syst, West Haven, CT 06516 USA.
Yale Univ, Sch Med, West Haven, CT 06516 USA.
Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA.
VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA.
Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
McGill Univ, Ctr Hlth, Montreal, PQ, Canada.
Atlanta VA Med Ctr, Atlanta, GA 30033 USA.
Emory Univ, Sch Med, Atlanta, GA USA.
Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA.
Baylor Coll Med, Houston, TX 77030 USA.
Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA.
Sheikh Khalifa Med City, Abu Dhabi, U Arab Emirates.
Washington DC VA Med Ctr, Washington, DC 20422 USA.
George Washington Univ, Med Ctr, Washington, DC 20037 USA.
James J Peters VA Med Ctr, New York, NY USA.
Mt Sinai Sch Med, New York, NY USA.
Rutgers State Univ, Newark, NJ 07103 USA.
RP Lo Re, V (reprint author), Univ Penn, Penn Ctr AIDS Res, Ctr Clin Epidemiol & Biostat, Div Infect Dis,Dept Med,Perelman Sch Med, 836 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA.
EM vincentl@mail.med.upenn.edu
RI Lo Re, Vincent/N-7817-2015;
OI Butt, Adeel/0000-0002-1118-1826; Goetz, Matthew/0000-0003-4542-992X
FU National Institute of Allergy and Infectious Diseases [K01 AI070001];
National Institute on Alcohol Abuse and Alcoholism [U01 AA13566];
National Institute of Mental Health [T32 MH020031]; National Institutes
of Health
FX National Institutes of Health.
NR 67
TC 71
Z9 71
U1 1
U2 8
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD MAR 18
PY 2014
VL 160
IS 6
BP 369
EP +
DI 10.7326/M13-1829
PG 14
WC Medicine, General & Internal
SC General & Internal Medicine
GA AD8MW
UT WOS:000333521300013
PM 24723077
ER
PT J
AU Wang, Y
Choueiri, TK
Lee, JL
Tan, MH
Rha, SY
North, SA
Kollmannsberger, CK
McDermott, DF
Heng, DYC
AF Wang, Y.
Choueiri, T. K.
Lee, J-L
Tan, M-H
Rha, S. Y.
North, S. A.
Kollmannsberger, C. K.
McDermott, D. F.
Heng, D. Y. C.
TI Anti-VEGF therapy in mRCC: differences between Asian and non-Asian
patients
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE sunitinib; sorafenib; ethnicity; VEGF; progression-free survival;
overall survival
ID RENAL-CELL CARCINOMA; JAPANESE PATIENTS; PHASE-II; INTERFERON-ALPHA;
SUNITINIB; EFFICACY; SAFETY; SORAFENIB; TOXICITY; CANCER
AB Background: Several reports suggest that vascular endothelial growth factor (VEGF)-targeted therapy in metastatic renal cell carcinoma (mRCC) may be more toxic in Asian vs non-Asian populations. Comparative efficacy of these agents with respect to ethnicity is not well characterised.
Methods: A multicentre, retrospective, cohort study using Asian and non-Asian centres which collected data on ethnicity, dose reductions and outcomes using the International mRCC Database Consortium.
Results: This study included 1024 (464 Asian, 560 non-Asian) patients with a 29.4 months median follow-up. The percentage of dose modifications/ reductions between non-Asians and Asians was similar (55% vs 61% P = 0.1197). When adjusted for risk groups, there was no difference in overall or progression-free survival between non-Asians and Asians. Patients with dose reductions due to toxicity had longer treatment durations and overall survival than those who did not in both non-Asian (10.6 vs 5.0 months, P<0.0001; 22.6 vs 16.1 months, P = 0.0016, respectively) and Asian populations (8.9 vs 5.4 months, P = 0.0028; 28.0 vs 18.7 months, P = 0.0069, respectively).
Conclusions: Adjusting for risk groups, there appears to be no difference in outcome between Asian vs non-Asian patients with mRCC treated with VEGF-targeted therapy. Judicious dose reductions may allow for better outcomes in both populations due to longer treatment durations, but direct comparisons are needed.
C1 [Wang, Y.] Univ Calgary, Calgary, AB, Canada.
[Choueiri, T. K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Kidney Canc Ctr,Dana Farber Canc Inst, Boston, MA 02115 USA.
[Lee, J-L] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul, South Korea.
[Tan, M-H] Natl Canc Ctr, Singapore, Singapore.
[Rha, S. Y.] Yonsei Univ, Coll Med, Yonsei Canc Ctr, Seoul, South Korea.
[North, S. A.] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada.
[Kollmannsberger, C. K.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
[McDermott, D. F.] Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Boston, MA USA.
[Heng, D. Y. C.] Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada.
RP Heng, DYC (reprint author), Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada.
EM daniel.heng@albertahealthservices.ca
FU (Alberta Health Services Cancer Care, British Columbia Cancer Agency);
Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center);
(Asan Medical Center, Yonsei Cancer Center); (National Cancer Center)
FX Authors would like to acknowledge the support they have received from
host institutions including cancer centres in Canada (Alberta Health
Services Cancer Care, British Columbia Cancer Agency), the United States
of America (Dana-Farber Cancer Institute, Beth Israel Deaconess Medical
Center), Korea (Asan Medical Center, Yonsei Cancer Center), and
Singapore (National Cancer Center).
NR 29
TC 8
Z9 8
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
EI 1532-1827
J9 BRIT J CANCER
JI Br. J. Cancer
PD MAR 18
PY 2014
VL 110
IS 6
BP 1433
EP 1437
DI 10.1038/bjc.2014.28
PG 5
WC Oncology
SC Oncology
GA AD4DB
UT WOS:000333195800005
PM 24548864
ER
PT J
AU Hirata, H
Hinoda, Y
Shahryari, V
Deng, G
Tanaka, Y
Tabatabai, ZL
Dahiya, R
AF Hirata, H.
Hinoda, Y.
Shahryari, V.
Deng, G.
Tanaka, Y.
Tabatabai, Z. L.
Dahiya, R.
TI Genistein downregulates onco-miR-1260b and upregulates sFRP1 and Smad4
via demethylation and histone modification in prostate cancer cells
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE genistein; miR-1260b; PC; sFRP1; Smad4; apoptosis
ID WNT SIGNALING PATHWAY; UNITED-STATES; EPIGENETIC INACTIVATION;
COLORECTAL-CANCER; INCIDENCE TRENDS; ALTERS GROWTH; GENES; METHYLATION;
PROGRESSION; EXPRESSION
AB Background: Recently several microRNAs (miRNAs) have been found to be regulated by genistein in cancer cells. In this study, we focused on the gene regulatory effect of genistein on microRNA and its target genes in prostate cancer (PC).
Methods: Initially, we investigated the effect of genistein on prostate cancer cells and identified that the expression of miRNA1260b was decreased by genistein. We performed functional analyses and investigated the relationship between miRNA-1260b expression and prostate cancer patient outcomes. Two target genes (sFRP1 and Smad4) of miR-1260b were identified based on computer algorithm and 3 ' UTR luciferase assay was carried out to determine direct miRNA regulation of the genes.
Results: Genistein promoted apoptosis while inhibiting prostate cancer cell proliferation, invasion and TCF reporter activity in PC cells. MiR-1260b was highly expressed in prostate cancer tissues and significantly downregulated by genistein in PC cells. After knocking down miR-1260b, cell proliferation, invasion, migration and TCF reporter activity were decreased in PC cells. Western analysis and 30UTR luciferase assay showed that the two target genes (sFRP1 and Smad4) were directly regulated by miR-1260b. The expression of sFRP1 and Smad4 was significantly decreased in prostate cancer tissues. Genistein also increased expression of these two genes via DNA demethylation and histone modifications.
Conclusions: Our data suggest that genistein exerts its anti-tumour effect via downregulation of miR-1260b that targeted sRRP1 and Smad4 genes in prostate cancer cells. The expression of sFRP1 and Smad4 was also modulated by genistein via DNA methylation or histone modifications in PC cell lines.
C1 [Hirata, H.; Shahryari, V.; Deng, G.; Tanaka, Y.; Dahiya, R.] San Francisco VA Med Ctr, Dept Urol, San Francisco, CA 94121 USA.
[Hirata, H.; Shahryari, V.; Deng, G.; Tanaka, Y.; Tabatabai, Z. L.; Dahiya, R.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Hinoda, Y.] Yamaguchi Univ, Grad Sch Med, Dept Oncol & Lab Med, Yamaguchi, Japan.
[Tabatabai, Z. L.] San Francisco VA Med Ctr, Dept Pathol, San Francisco, CA USA.
RP Dahiya, R (reprint author), San Francisco VA Med Ctr, Dept Urol, San Francisco, CA 94121 USA.
EM rdahiya@urology.ucsf.edu
FU National Center for Research Resources of the National Institutes of
Health [RO1CA138642, RO1CA130860, RO1CA160079, I01BX001123]; VA Merit
Review, VA Program Project; Yamada Science Foundation
FX We thank Dr Roger Erickson for his support and assistance with the
preparation of the manuscript. This study was supported by National
Center for Research Resources of the National Institutes of Health
through Grant Number RO1CA138642, RO1CA130860, RO1CA160079, I01BX001123,
VA Merit Review, VA Program Project (PI: R Dahiya) and Yamada Science
Foundation.
NR 46
TC 19
Z9 22
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
EI 1532-1827
J9 BRIT J CANCER
JI Br. J. Cancer
PD MAR 18
PY 2014
VL 110
IS 6
BP 1645
EP 1654
DI 10.1038/bjc.2014.48
PG 10
WC Oncology
SC Oncology
GA AD4DB
UT WOS:000333195800029
PM 24504368
ER
PT J
AU Li, XY
Tao, H
Xie, KW
Ni, ZH
Yan, YC
Wei, K
Chuang, PY
He, JC
Gu, LY
AF Li, Xiaoying
Tao, Hua
Xie, Kewei
Ni, Zhaohui
Yan, Yucheng
Wei, Kai
Chuang, Peter Y.
He, John Cijiang
Gu, Leyi
TI cAMP Signaling Prevents Podocyte Apoptosis via Activation of Protein
Kinase A and Mitochondrial Fusion
SO PLOS ONE
LA English
DT Article
ID GLOMERULAR PODOCYTES; EPITHELIAL-CELLS; MOUSE MODEL; IN-VITRO; PATHWAY;
EXPRESSION; RECEPTOR; NEPHROPATHY; DAMAGE; STRESS
AB Our previous in vitro studies suggested that cyclic AMP (cAMP) signaling prevents adriamycin (ADR) and puromycin aminonucleoside (PAN)-induced apoptosis in podocytes. As cAMP is an important second messenger and plays a key role in cell proliferation, differentiation and cytoskeleton formation via protein kinase A (PKA) or exchange protein directly activated by cAMP (Epac) pathways, we sought to determine the role of PKA or Epac signaling in cAMP-mediated protection of podocytes. In the ADR nephrosis model, we found that forskolin, a selective activator of adenylate cyclase, attenuated albuminuria and improved the expression of podocyte marker WT-1. When podocytes were treated with pCPT-cAMP (a selective cAMP/PKA activator), PKA activation was increased in a time-dependent manner and prevented PAN-induced podocyte loss and caspase 3 activation, as well as a reduction in mitochondrial membrane potential. We found that PAN and ADR resulted in a decrease in Mfn1 expression and mitochondrial fission in podocytes. pCPT-cAMP restored Mfn1 expression in puromycin or ADR-treated podocytes and induced Drp1 phosphorylation, as well as mitochondrial fusion. Treating podocytes with arachidonic acid resulted in mitochondrial fission, podocyte loss and cleaved caspase 3 production. Arachidonic acid abolished the protective effects of pCPT-cAMP on PAN-treated podocytes. Mdivi, a mitochondrial division inhibitor, prevented PAN-induced cleaved caspase 3 production in podocytes. We conclude that activation of cAMP alleviated murine podocyte caused by ADR. PKA signaling resulted in mitochondrial fusion in podocytes, which at least partially mediated the effects of cAMP.
C1 [Li, Xiaoying; Tao, Hua; Xie, Kewei; Ni, Zhaohui; Yan, Yucheng; Wei, Kai; Gu, Leyi] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Div Renal, Shanghai 200030, Peoples R China.
[Li, Xiaoying; Tao, Hua; Xie, Kewei; Ni, Zhaohui; Yan, Yucheng; Wei, Kai; Gu, Leyi] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Mol Cell Lab Kidney Dis, Shanghai 200030, Peoples R China.
[Chuang, Peter Y.; He, John Cijiang] Icahn Sch Med Mt Sinai, Div Nephrol, New York, NY USA.
[He, John Cijiang] James J Peter Vet Affairs Med Ctr, Renal Sect, Bronx, NY USA.
RP Gu, LY (reprint author), Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Div Renal, Shanghai 200030, Peoples R China.
EM guleyi@aliyun.com
FU National Nature Science Foundation Grant of China [30971363, 81270781];
Nature Science Foundation Grant of Shanghai [08ZR1413200]; National
Basic Research Program of China 973 Program [2012CB517602]; Nature
Science Foundation of Shanghai [10JC1410200]
FX This work was supported by the National Nature Science Foundation Grant
of China (30971363 and 81270781, http://www.nsfc.gov.cn) and Nature
Science Foundation Grant of Shanghai (08ZR1413200,
http://www.stcsm.gov.cn) to Dr Gu. National Basic Research Program of
China 973 Program (2012CB517602,http://program.most.gov.cn) to Dr Ni as
well as by a grant (10JC1410200,http://www.stcsm.gov.cn) from the Nature
Science Foundation of Shanghai to Dr Yan. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparaton of the manuscript.
NR 43
TC 6
Z9 8
U1 1
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 18
PY 2014
VL 9
IS 3
AR e92003
DI 10.1371/journal.pone.0092003
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD4ZE
UT WOS:000333259900058
PM 24642777
ER
PT J
AU Anderson, RF
Shinde, SS
Hille, R
Rothery, RA
Weiner, JH
Rajagukguk, S
Maldashina, E
Cecchini, G
AF Anderson, Robert F.
Shinde, Sujata S.
Hille, Russ
Rothery, Richard A.
Weiner, Joel H.
Rajagukguk, Sany
Maldashina, Elena
Cecchini, Gary
TI Electron-Transfer Pathways in the Heme and Quinone-Binding Domain of
Complex II (Succinate Dehydrogenase)
SO BIOCHEMISTRY
LA English
DT Article
ID ESCHERICHIA-COLI; UBIQUINONE OXIDOREDUCTASE; FUMARATE REDUCTASE;
CATALYTIC-ACTIVITY; RESPIRATORY-CHAIN; SITE; PARAGANGLIOMAS; SUPEROXIDE;
MUTATIONS; OXIDASE
AB Single electron transfers have been examined in complex II (succinate:ubiquinone oxidoreductase) by the method of pulse radiolysis. Electrons are introduced into the enzyme initially at the [3Fe-4S] and ubiquinone sites followed. by intramolecular equilibration with the b heme of the enzyme. To define thermodynamic and other controlling parameters for the pathways of electron transfer in complex II, site-directed variants were constructed and analyzed. Variants at SdhB-His207 and SdhB-Ile209 exhibit significantly perturbed electron transfer between the [3Fe-4S] cluster and ubiquinone. Analysis of the data using Marcus theory shows that the electronic coupling constants for wild-type and variant enzyme are all small, indicating that electron transfer occurs by diabatic tunneling. The presence of the ubiquinone is necessary for efficient electron transfer to the heme, which only slowly equilibrates with the [3Fe-4S] cluster in the absence of the quinone.
C1 [Anderson, Robert F.; Shinde, Sujata S.] Univ Auckland, Fac Med & Hlth Sci, Auckland Canc Soc Res Ctr, Auckland 1142, New Zealand.
[Hille, Russ] Univ Calif Riverside, Dept Biochem, Riverside, CA 92521 USA.
[Rothery, Richard A.; Weiner, Joel H.] Univ Alberta, Dept Biochem, Membrane Protein Res Grp, Edmonton, AB T6G 2H7, Canada.
[Rajagukguk, Sany; Maldashina, Elena; Cecchini, Gary] San Francisco VA Med Ctr, Div Mol Biol, San Francisco, CA 94121 USA.
[Maldashina, Elena; Cecchini, Gary] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
RP Cecchini, G (reprint author), Univ Auckland, Fac Med & Hlth Sci, Auckland Canc Soc Res Ctr, Auckland 1142, New Zealand.
EM r.anderson@auckland.ac.nz; gary.cecchini@ucsf.edu
FU Department of Veterans Affairs Biomedical Laboratory Research and
Development Merit Award [BX001077]; National Institutes of Health
[GM61606]; U.S. Department of Energy [DE-SC0010666]; Canadian Institutes
of Health Research [MOP89735]
FX The work in the authors' laboratories was supported in whole or in part
by the Department of Veterans Affairs Biomedical Laboratory Research and
Development Merit Award (BX001077), the National Institutes of Health
(GM61606), the U.S. Department of Energy (DE-SC0010666), and the
Canadian Institutes of Health Research (MOP89735).
NR 49
TC 1
Z9 1
U1 2
U2 30
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD MAR 18
PY 2014
VL 53
IS 10
BP 1637
EP 1646
DI 10.1021/bi401630m
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AD4QM
UT WOS:000333235600012
PM 24559074
ER
PT J
AU Seely, EW
Ecker, J
AF Seely, Ellen W.
Ecker, Jeffrey
TI Chronic Hypertension in Pregnancy
SO CIRCULATION
LA English
DT Article
DE hypertension; pre-eclampsia; pregnancy; pregnancy complications
ID CONVERTING ENZYME-INHIBITORS; DIETARY-SODIUM RESTRICTION; HIGH
BLOOD-PRESSURE; DEVELOPMENTAL TOXICITY; RECEPTOR ANTAGONISTS; PREVENT
PREECLAMPSIA; 1ST TRIMESTER; RISK-FACTORS; WOMEN; MANAGEMENT
C1 [Seely, Ellen W.] Harvard Univ, Brigham & Womens Hosp, Endocrinol Diabet & Hypertens Div, Sch Med, Boston, MA 02115 USA.
[Ecker, Jeffrey] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Maternal Fetal Med, Boston, MA USA.
RP Seely, EW (reprint author), Brigham & Womens Hosp, Endocrinol Diabet & Hypertens Div, 221 Longwood Ave, Boston, MA 02115 USA.
EM eseely@partners.org
FU Bayer Health Care
FX Dr Seely received support from Bayer Health Care for an
investigator-initiated study of postmenopausal women ending in 2012. Dr
Ecker reports no conflicts.
NR 63
TC 15
Z9 16
U1 1
U2 13
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 18
PY 2014
VL 129
IS 11
BP 1254
EP 1261
DI 10.1161/CIRCULATIONAHA.113.003904
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AD3MN
UT WOS:000333145200015
PM 24637432
ER
PT J
AU Pishesha, N
Thiru, P
Shi, JH
Eng, JC
Sankaran, VG
Lodish, HF
AF Pishesha, Novalia
Thiru, Prathapan
Shi, Jiahai
Eng, Jennifer C.
Sankaran, Vijay G.
Lodish, Harvey F.
TI Transcriptional divergence and conservation of human and mouse
erythropoiesis
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE hematopoiesis; comparative genomics; microarray
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ANEMIA TYPE-II; ERYTHROID-DIFFERENTIATION;
HUMAN IMMUNOLOGY; GENE-EXPRESSION; DISTINCT STAGES; HEMATOPOIESIS;
MUTATIONS; COPII; CELLS
AB Mouse models have been used extensively for decades and have been instrumental in improving our understanding of mammalian erythropoiesis. Nonetheless, there are several examples of variation between human and mouse erythropoiesis. We performed a comparative global gene expression study using data from morphologically identical stage-matched sorted populations of human and mouse erythroid precursors from early to late erythroblasts. Induction and repression of major transcriptional regulators of erythropoiesis, as well as major erythroid-important proteins, are largely conserved between the species. In contrast, at a global level we identified a significant extent of divergence between the species, both at comparable stages and in the transitions between stages, especially for the 500 most highly expressed genes during development. This suggests that the response of multiple developmentally regulated genes to key erythroid transcriptional regulators represents an important modification that has occurred in the course of erythroid evolution. In developing a systematic framework to understand and study conservation and divergence between human and mouse erythropoiesis, we show how mouse models can fail to mimic specific human diseases and provide predictions for translating findings from mouse models to potential therapies for human disease.
C1 [Pishesha, Novalia; Thiru, Prathapan; Shi, Jiahai; Eng, Jennifer C.; Sankaran, Vijay G.; Lodish, Harvey F.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
[Pishesha, Novalia; Lodish, Harvey F.] MIT, Dept Biol Engn, Cambridge, MA 02142 USA.
[Lodish, Harvey F.] MIT, Dept Biol, Cambridge, MA 02142 USA.
[Sankaran, Vijay G.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Sankaran, Vijay G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Sankaran, Vijay G.; Lodish, Harvey F.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
RP Sankaran, VG (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
EM sankaran@broadinstitute.org; lodish@wi.mit.edu
RI shi, jiahai/D-7650-2013
OI shi, jiahai/0000-0002-6467-8289
FU National Institutes of Health (NIH) [P01 HL32262, T32 HL007574-30];
Schlumberger Foundation Faculty for the Future; American Association of
University Women International Fellowship; Philanthropic Educational
Organization International Peace Scholarship Fund
FX We thank Tom DiCesare for assistance with illustrations and Marko Knoll
and Leif Si-Hun Ludwig for discussion and critical proofreading of the
manuscript. This work was supported by National Institutes of Health
(NIH) Grants P01 HL32262 (to H. F. L.) and T32 HL007574-30 (to V. G.
S.). N.P. was supported by grants from the Schlumberger Foundation
Faculty for the Future, the American Association of University Women
International Fellowship, and the Philanthropic Educational Organization
International Peace Scholarship Fund.
NR 46
TC 21
Z9 21
U1 0
U2 9
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 18
PY 2014
VL 111
IS 11
BP 4103
EP 4108
DI 10.1073/pnas.1401598111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD1XV
UT WOS:000333027900054
PM 24591581
ER
PT J
AU Lakkireddy, D
Reddy, YM
Di Biase, L
Vallakati, A
Mansour, MC
Santangeli, P
Gangireddy, S
Swarup, V
Chalhoub, F
Atkins, D
Bommana, S
Verma, A
Sanchez, JE
Burkhardt, JD
Barrett, CD
Baheiry, S
Ruskin, J
Reddy, V
Natale, A
AF Lakkireddy, Dhanunjaya
Reddy, Yeruva Madhu
Di Biase, Luigi
Vallakati, Ajay
Mansour, Moussa C.
Santangeli, Pasquale
Gangireddy, Sandeep
Swarup, Vijay
Chalhoub, Fadi
Atkins, Donita
Bommana, Sudharani
Verma, Atul
Sanchez, Javier E.
Burkhardt, J. David
Barrett, Conor D.
Baheiry, Salwa
Ruskin, Jeremy
Reddy, Vivek
Natale, Andrea
TI Feasibility and Safety of Uninterrupted Rivaroxaban for Periprocedural
Anticoagulation in Patients Undergoing Radiofrequency Ablation for
Atrial Fibrillation
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE periprocedural anticoagulation; radiofrequency ablation; rivaroxaban;
warfarin
ID INTERNATIONAL NORMALIZED RATIO; CATHETER ABLATION; ORAL ANTICOAGULANTS;
DABIGATRAN; WARFARIN; COMPLICATIONS; PHARMACODYNAMICS; PHARMACOKINETICS;
MANAGEMENT; THROMBOEMBOLISM
AB Objectives The purpose of this study was to evaluate the feasibility and safety of uninterrupted rivaroxaban therapy during atrial fibrillation (AF) ablation.
Background Optimal periprocedural anticoagulation strategy is essential for minimizing bleeding and thromboembolic complications during and after AF ablation. The safety and efficacy of uninterrupted rivaroxaban therapy as a periprocedural anticoagulant for AF ablation are unknown.
Methods We performed a multicenter, observational, prospective study of a registry of patients undergoing AF ablation in 8 centers in North America. Patients taking uninterrupted periprocedural rivaroxaban were matched by age, sex, and type of AF with an equal number of patients taking uninterrupted warfarin therapy who were undergoing AF ablation during the same period.
Results A total of 642 patients were included in the study, with 321 in each group. Mean age was 63 +/- 10 years, with 442 (69%) males and 328 (51%) patients with paroxysmal AF equally distributed between the 2 groups. Patients in the warfarin group had a slightly higher mean HAS- BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly) score (1.70 +/- 1.0 vs. 1.47 +/- 0.9, respectively; p = 0.032). Bleeding and embolic complications occurred in 47 (7.3%) and 2 (0.3%) patients (both had transient ischemic attacks) respectively. There were no differences in the number of major bleeding complications (5 [1.6%] vs. 7 [1.9%], respectively; p = 0.772), minor bleeding complications (16 [5.0%] vs. 19 [5.9%], respectively; p = 0.602), or embolic complications (1 [0.3%] vs. 1 [0.3%], respectively; p = 1.0) between the rivaroxaban and warfarin groups in the first 30 days.
Conclusions Uninterrupted rivaroxaban therapy appears to be as safe and efficacious in preventing bleeding and thromboembolic events in patients undergoing AF ablation as uninterrupted warfarin therapy. (C) 2014 by the American College of Cardiology Foundation
C1 [Lakkireddy, Dhanunjaya; Reddy, Yeruva Madhu; Vallakati, Ajay; Atkins, Donita; Bommana, Sudharani] Univ Kansas Hosp & Med Ctr, Cardiovasc Res Inst, Div Cardiovasc Dis, Mid Amer Cardiol, Kansas City, KS USA.
Texas Cardiac Arrhythmia Inst, Austin, TX USA.
[Di Biase, Luigi] Univ Foggia, Dept Cardiol, Foggia, Italy.
[Di Biase, Luigi; Natale, Andrea] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA.
[Mansour, Moussa C.; Chalhoub, Fadi; Ruskin, Jeremy] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Gangireddy, Sandeep; Reddy, Vivek] Mt Sinai Med Ctr, New York, NY 10029 USA.
[Swarup, Vijay] Arizona Heart Rhythm Ctr, Phoenix, AZ USA.
[Verma, Atul] Southlake Reg Med Ctr, Toronto, ON, Canada.
[Baheiry, Salwa] Calif Pacific Med Ctr, San Francisco, CA USA.
[Barrett, Conor D.] St Lukes Roosevelt Hosp, New York, NY 10025 USA.
RP Lakkireddy, D (reprint author), Univ Kansas, Cardiovasc Res Inst, 3901 Rainbow Blvd,MS 4023, Kansas City, KS 66160 USA.
EM dlakkireddy@kumc.edu
FU consultant with Biosense Webster; Bristol-Myers Squibb; Boston
Scientific; Medtronic; Pfizer; Sanofi-Aventis; St. Jude Medical;
Advanced Medical Education
FX From the *Division of Cardiovascular Diseases, Cardiovascular Research
Institute, Mid America Cardiology, University of Kansas Hospital &
Medical Center, Kansas City, Kansas; |Texas Cardiac Arrhythmia
Institute, Austin, Texas; double dagger Department of Cardiology,
University of Foggia, Foggia, Italy; Department of Biomedical
Engineering, University of Texas, Austin, Texas; parallel to
Massachusetts General Hospital, Boston, Massachusetts; Mount Sinai
Medical Center, New York, New York; #Arizona Heart Rhythm Center,
Phoenix, Arizona; **Southlake Regional Medical Center, Toronto, Ontario,
Canada; dagger dagger California Pacific Medical Center, San Francisco,
California; and the double dagger double dagger St. Lukes Roosevelt
Hospital, New York, New York. Dr. Lakkireddy has received speaker
honoraria from St. JudeMedical, Boehringer Ingelheim, Jansen, and
Bristol Meyers Squibb. Dr. Di Biase is a consultant for Hansen Medical,
St. JudeMedical, and Biosense Webster. Dr. Mansour received research
grants from Biosense Webster, St. Jude Medical, Boston Scientific, and
MC 10. Dr. Swarup has a research relationship with Biosense Webster, St.
Jude Medical, Boston Scientific, Medtronic, and Biotronik. Dr. Verma
serves on the advisory boards of Bayer, Boehringer Ingelheim, and
Pfizer. Dr. Sanchez has received speaker fees from Janssen. Dr.
Burkhardt is a speaker for Boehringer Ingelheim and a consultant with
Biosense Webster. Dr. Ruskin has received fellowship grants and/or is a
consultant with Biosense Webster, Bristol-Myers Squibb, Boston
Scientific, Medtronic, Pfizer, Sanofi-Aventis, St. Jude Medical, and
Advanced Medical Education. Dr. Natale is a consultant with Medtronic,
BiosenseWebster, Boston Scientific, St. Jude Medical, and Biotronik. All
other authors have reported that they have no relationships relevant to
the contents of this paper to disclose. Drs. Lakkireddy and Reddy
contributed equally and are primary coauthors of the manuscript.
NR 38
TC 79
Z9 83
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 18
PY 2014
VL 63
IS 10
BP 982
EP 988
DI 10.1016/j.jacc.2013.11.039
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AC4ZG
UT WOS:000332529400007
PM 24412445
ER
PT J
AU Hawkins, BM
McCoy, LA
Neely, ML
Adusumalli, S
Messenger, JC
Drachman, DE
Bass, TA
O'Gara, PT
Rao, SV
Yeh, RW
AF Hawkins, Beau M.
McCoy, Lisa A.
Neely, Megan L.
Adusumalli, Srinath
Messenger, John C.
Drachman, Douglas E.
Bass, Theodore A.
O'Gara, Patrick T.
Rao, Sunil V.
Yeh, Robert W.
TI Impact of Academic Year Timing on Percutaneous Coronary Intervention
Outcomes at Training Institutions
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Letter
C1 [Yeh, Robert W.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Hawkins, Beau M.] Univ Oklahoma, Hlth Sci Ctr, Dept Internal Med, Cardiovasc Sect, Oklahoma City, OK USA.
[McCoy, Lisa A.; Neely, Megan L.; Rao, Sunil V.] Duke Clin Res Inst, Durham, NC USA.
[Adusumalli, Srinath; Drachman, Douglas E.; Yeh, Robert W.] Massachusetts Gen Hosp, Div Cardiol, Dept Internal Med, Boston, MA 02114 USA.
[Messenger, John C.] Univ Colorado Hosp Denver, Dept Med, Aurora, CO USA.
[Messenger, John C.] Hlth Sci Ctr, Aurora, CO USA.
[Bass, Theodore A.] Univ Florida, Coll Med Jacksonville, Jacksonville, FL USA.
[O'Gara, Patrick T.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA.
RP Yeh, RW (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St GRB 800, Boston, MA 02114 USA.
EM ryeh@partners.org
NR 6
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 18
PY 2014
VL 63
IS 10
BP 1025
EP 1026
DI 10.1016/j.jacc.2013.11.019
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AC4ZG
UT WOS:000332529400016
PM 24333492
ER
PT J
AU Preti, MG
Makris, N
Papadimitriou, G
Lagana, MM
Griffanti, L
Clerici, M
Nemni, R
Westin, CF
Baselli, G
Baglio, F
AF Preti, Maria Giulia
Makris, Nikos
Papadimitriou, George
Lagana, Maria Marcella
Griffanti, Ludovica
Clerici, Mario
Nemni, Raffaello
Westin, Carl-Fredrik
Baselli, Giuseppe
Baglio, Francesca
TI A Novel Approach of Groupwise fMRI-Guided Tractography Allowing to
Characterize the Clinical Evolution of Alzheimer's Disease
SO PLOS ONE
LA English
DT Article
ID MILD COGNITIVE IMPAIRMENT; ASSOCIATION WORKGROUPS; DIAGNOSTIC
GUIDELINES; NATIONAL INSTITUTE; BRAIN ACTIVATION; DIFFUSION; DTI;
RECOMMENDATIONS; DISCONNECTION; DEMENTIA
AB Guiding diffusion tract-based anatomy by functional magnetic resonance imaging (fMRI), we aim to investigate the relationship between structural connectivity and functional activity in the human brain. To this purpose, we introduced a novel groupwise fMRI-guided tractographic approach, that was applied on a population ranging between prodromic and moderate stages of Alzheimer's disease (AD). The study comprised of 15 subjects affected by amnestic mild cognitive impairment (aMCI), 14 diagnosed with AD and 14 elderly healthy adults who were used as controls. By creating representative (ensemble) functionally guided tracts within each group of participants, our methodology highlighted the white matter fiber connections involved in verbal fluency functions for a specific population, and hypothesized on brain compensation mechanisms that potentially counteract or reduce cognitive impairment symptoms in prodromic AD. Our hope is that this fMRI-guided tractographic approach could have potential impact in various clinical studies, while investigating white/gray matter connectivity, in both health and disease.
C1 [Preti, Maria Giulia; Lagana, Maria Marcella; Griffanti, Ludovica; Clerici, Mario; Nemni, Raffaello; Baglio, Francesca] Fdn Don Carlo Gnocchi ONLUS, IRCCS, Milan, Italy.
[Preti, Maria Giulia; Griffanti, Ludovica; Baselli, Giuseppe] Politecn Milan, Dept Elect Informat & Bioengn, I-20133 Milan, Italy.
[Makris, Nikos; Papadimitriou, George] Harvard Univ, Sch Med, Dept Psychiat,Massachusetts Gen Hosp, Ctr Neural Syst Invest,Ctr Morphometr Anal,Athino, Boston, MA 02115 USA.
[Makris, Nikos; Papadimitriou, George] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Neur, Ctr Neural Syst Invest,Ctr Morphometr Anal,Sch Me, Boston, MA USA.
[Makris, Nikos] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat,Psychiat Neuroimaging Lab, Boston, MA 02115 USA.
[Makris, Nikos] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA.
[Clerici, Mario; Nemni, Raffaello] Univ Milan, Dept Pathophysiol & Transplantat, Milan, Italy.
[Westin, Carl-Fredrik] Brigham & Womens Hosp, Dept Radiol, Lab Math Imaging, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Preti, MG (reprint author), Fdn Don Carlo Gnocchi ONLUS, IRCCS, Milan, Italy.
EM gpreti@dongnocchi.it
RI Baglio, Francesca/K-2808-2016;
OI Baglio, Francesca/0000-0002-6145-5274; Clerici,
Mario/0000-0001-5920-6191; Griffanti, Ludovica/0000-0002-0540-9353
FU Ricerca Corrente; Italian Ministry of Health; National Institutes of
Health (NIH) [R01MH074794, P41EB015902, R01AG042512, R01DA027804,
R21NS079905, R21NS077059]
FX The study was supported by 2011-2012 Ricerca Corrente, Italian Ministry
of Health (http://www.salute.gov.it/portale/temi/p2_5. jsp?lingua =
italiano&area = Ricerca%20sanita ria&menu = corrente), National
Institutes of Health (NIH) R01MH074794, NIH P41EB015902, NIH
R01AG042512, NIH R01DA027804, NIH R21NS079905 and NIH R21NS077059. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 39
TC 4
Z9 4
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 17
PY 2014
VL 9
IS 3
AR e92026
DI 10.1371/journal.pone.0092026
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AD4XD
UT WOS:000333254100102
PM 24637718
ER
PT J
AU Gutierrez, A
Roderick, JE
Kelliher, MA
AF Gutierrez, Alejandro
Roderick, Justine E.
Kelliher, Michelle A.
TI Leukemia Propagating Cells Akt Up
SO CANCER CELL
LA English
DT Editorial Material
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; GLUCOCORTICOID RESISTANCE; INITIATING
CELLS
C1 [Gutierrez, Alejandro] Boston Childrens Hosp, Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA.
[Gutierrez, Alejandro] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Roderick, Justine E.; Kelliher, Michelle A.] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA.
RP Gutierrez, A (reprint author), Boston Childrens Hosp, Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA.
EM alejandro.gutierrez@childrens.harvard.edu;
michelle.kelliher@umassmed.edu
FU NCI NIH HHS [R01 CA096899]
NR 11
TC 2
Z9 2
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
EI 1878-3686
J9 CANCER CELL
JI Cancer Cell
PD MAR 17
PY 2014
VL 25
IS 3
BP 263
EP 265
DI 10.1016/j.ccr.2014.02.022
PG 3
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA AD4PQ
UT WOS:000333233400003
PM 24651006
ER
PT J
AU Arteaga, CL
Engelman, JA
AF Arteaga, Carlos L.
Engelman, Jeffrey A.
TI ERBB Receptors: From Oncogene Discovery to Basic Science to
Mechanism-Based Cancer Therapeutics
SO CANCER CELL
LA English
DT Article
ID EPIDERMAL-GROWTH-FACTOR; CELL LUNG-CANCER; METASTATIC BREAST-CANCER;
TYROSINE KINASE INHIBITOR; GENE COPY NUMBER; PERTUZUMAB PLUS
TRASTUZUMAB; POLARIZED EPITHELIAL-CELLS; MUTANT COLORECTAL CANCERS;
FACTOR-I RECEPTOR; ACQUIRED-RESISTANCE
AB ERBB receptors were linked to human cancer pathogenesis approximately three decades ago. Biomedical investigators have since developed substantial understanding of the biology underlying the dependence of cancers on aberrant ERBB receptor signaling. An array of cancer-associated genetic alterations in ERBB receptors has also been identified. These findings have led to the discovery and development of mechanism-based therapies targeting ERBB receptors that have improved outcome for many cancer patients. In this Perspective, we discuss current paradigms of targeting ERBB receptors with cancer therapeutics and our understanding of mechanisms of action and resistance to these drugs. As current strategies still have limitations, we also discuss challenges and opportunities that lie ahead as basic scientists and clinical investigators work toward more breakthroughs.
C1 [Arteaga, Carlos L.] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA.
[Engelman, Jeffrey A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
RP Arteaga, CL (reprint author), Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA.
EM carlos.arteaga@vanderbilt.edu; jengelman@mgh.harvard.edu
RI Mendez, Pedro /J-8955-2016
OI Mendez, Pedro /0000-0001-6713-7907
FU NCI [R01 CA80195, R01 CA137008, R01 CA164273, R01 CA140954]; ACS
Clinical Research Professorship Grant [CRP-07-234]; Breast Cancer SPORE
grant [P50 CA98131]; GI Cancer SPORE grant [P50 CA127003]; Department of
Defense; Vanderbilt-Ingram Cancer Center Support grant [P30 CA68485]
FX This work was supported by NCI grants R01 CA80195 (C.L.A.), R01 CA137008
(J.A.E.), R01 CA164273 (J.A.E.), and R01 CA140954 (J.A.E.), ACS Clinical
Research Professorship Grant CRP-07-234 (CIA.), Breast Cancer SPORE
grant P50 CA98131, GI Cancer SPORE grant P50 CA127003, the Department of
Defense (J.A.E.), and Vanderbilt-Ingram Cancer Center Support grant P30
CA68485.
NR 219
TC 172
Z9 177
U1 8
U2 40
PU CELL PRESS
PI CAMBRIDGE
PA 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA
SN 1535-6108
EI 1878-3686
J9 CANCER CELL
JI Cancer Cell
PD MAR 17
PY 2014
VL 25
IS 3
BP 282
EP 303
DI 10.1016/j.ccr.2014.02.025
PG 22
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA AD4PQ
UT WOS:000333233400008
PM 24651011
ER
PT J
AU Blackburn, JS
Liu, SL
Wilder, JL
Dobrinski, KP
Lobbardi, R
Moore, FE
Martinez, SA
Chen, EY
Lee, C
Langenau, DM
AF Blackburn, Jessica S.
Liu, Sali
Wilder, Jayme L.
Dobrinski, Kimberly P.
Lobbardi, Riadh
Moore, Finola E.
Martinez, Sarah A.
Chen, Eleanor Y.
Lee, Charles
Langenau, David M.
TI Clonal Evolution Enhances Leukemia-Propagating Cell Frequency in T Cell
Acute Lymphoblastic Leukemia through Akt/mTORC1 Pathway Activation
SO CANCER CELL
LA English
DT Article
ID GLUCOCORTICOID RESISTANCE; INHIBITOR NVP-BEZ235; INITIATING CELLS;
CANCER MEDICINE; PTEN; MYC; HETEROGENEITY; ZEBRAFISH; RELAPSE; TRIAL
AB Clonal evolution and intratumoral heterogeneity drive cancer progression through unknown molecular mechanisms. To address this issue, functional differences between single T cell acute lymphoblastic leukemia (T-ALL) clones were assessed using a zebrafish transgenic model. Functional variation was observed within individual clones, with a minority of clones enhancing growth rate and leukemia-propagating potential with time. Akt pathway activation was acquired in a subset of these evolved clones, which increased the number of leukemia-propagating cells through activating mTORC1, elevated growth rate likely by stabilizing the Myc protein, and rendered cells resistant to dexamethasone, which was reversed by combined treatment with an Akt inhibitor. Thus, T-ALL clones spontaneously and continuously evolve to drive leukemia progression even in the absence of therapy-induced selection.
C1 [Blackburn, Jessica S.; Lobbardi, Riadh; Moore, Finola E.; Martinez, Sarah A.; Chen, Eleanor Y.; Langenau, David M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Blackburn, Jessica S.; Lobbardi, Riadh; Moore, Finola E.; Martinez, Sarah A.; Chen, Eleanor Y.; Langenau, David M.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA.
[Blackburn, Jessica S.; Wilder, Jayme L.; Lobbardi, Riadh; Moore, Finola E.; Chen, Eleanor Y.; Langenau, David M.] Harvard Stem Cell Inst, Boston, MA 02138 USA.
[Liu, Sali] Northwestern Univ, Chicago, IL 60208 USA.
[Dobrinski, Kimberly P.] Univ S Florida, Ctr Integrat Med, Tampa, FL 33620 USA.
[Chen, Eleanor Y.] Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA.
[Lee, Charles] Jackson Lab Genom Med, Farmington, CT 06030 USA.
[Lee, Charles] Seoul Natl Univ, Sch Med, Dept Grad Studies, Seoul 110744, South Korea.
RP Langenau, DM (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
EM dlangenau@mgh.harvard.edu
FU Alex Lemonade Stand Foundation; Leukemia and Lymphoma Society;
Massachusetts General Hospital Toteson Fund for Medical Discovery
Postdoctoral Fellowship; National Institutes of Health (NIH)
[1K99CA181500-01]; NIH [F32DK098875, R01-GM081533, U01-HG005725];
American Cancer Society; Leukemia Research Foundation; Harvard Stem Cell
Institute; MGH Goodman Fellowship
FX We thank Dr. Ravi Mylvaganam for expert advice and assistance with FAGS
and Eric Stone and Marcellino Pena for excellent zebrafish husbandry. We
thank Dr. Alejandro Gutierrez and Dr. Hui Feng for reagents and
technical advice and Dr. Donna Neuberg for assistance with statistical
analyses. J.S.B. is supported by the Alex Lemonade Stand Foundation
Young Investigator Award, the Leukemia and Lymphoma Society Special
Fellow Award, the Massachusetts General Hospital Toteson Fund for
Medical Discovery Postdoctoral Fellowship, and National Institutes of
Health (NIH) grant 1K99CA181500-01. F.E.M. is supported by NIH grant
F32DK098875. C.L. received support from NIH grants R01-GM081533 and
U01-HG005725. D.M.L. received funding for this project from the American
Cancer Society, the Leukemia Research Foundation, the Harvard Stem Cell
Institute, the MGH Goodman Fellowship, and the Alex Lemonade Stand
Foundation Innovation Grant.
NR 41
TC 26
Z9 29
U1 2
U2 14
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
EI 1878-3686
J9 CANCER CELL
JI Cancer Cell
PD MAR 17
PY 2014
VL 25
IS 3
BP 366
EP 378
DI 10.1016/j.ccr.2014.01.032
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA AD4PQ
UT WOS:000333233400013
PM 24613413
ER
PT J
AU Kool, M
Jones, DTW
Jager, N
Northcott, PA
Pugh, TJ
Hovestadt, V
Piro, RM
Esparza, LA
Markant, SL
Remke, M
Milde, T
Bourdeaut, F
Ryzhova, M
Sturm, D
Pfaff, E
Stark, S
Hutter, S
Seker-Cin, H
Johann, P
Bender, S
Schmidt, C
Rausch, T
Shih, D
Reimand, J
Sieber, L
Wittmann, A
Linke, L
Witt, H
Weber, UD
Zapatka, M
Konig, R
Beroukhim, R
Bergthold, G
van Sluis, P
Volckmann, R
Koster, J
Versteeg, R
Schmidt, S
Wolf, S
Lawerenz, C
Bartholomae, CC
von Kalle, C
Unterberg, A
Herold-Mende, C
Hofer, S
Kulozik, AE
von Deimling, A
Scheurlen, W
Felsberg, J
Reifenberger, G
Hasselblatt, M
Crawford, JR
Grant, GA
Jabado, N
Perry, A
Cowdrey, C
Croul, S
Zadeh, G
Korbel, JO
Doz, F
Delattre, O
Bader, GD
McCabe, MG
Collins, VP
Kieran, MW
Cho, YJ
Pomeroy, SL
Witt, O
Brors, B
Taylor, MD
Schuller, U
Korshunov, A
Eils, R
Wechsler-Reya, RJ
Lichter, P
Pfister, SM
AF Kool, Marcel
Jones, David T. W.
Jaeger, Natalie
Northcott, Paul A.
Pugh, Trevor J.
Hovestadt, Volker
Piro, Rosario M.
Esparza, L. Adriana
Markant, Shirley L.
Remke, Marc
Milde, Till
Bourdeaut, Franck
Ryzhova, Marina
Sturm, Dominik
Pfaff, Elke
Stark, Sebastian
Hutter, Sonja
Seker-Cin, Huriye
Johann, Pascal
Bender, Sebastian
Schmidt, Christin
Rausch, Tobias
Shih, David
Reimand, Jueri
Sieber, Laura
Wittmann, Andrea
Linke, Linda
Witt, Hendrik
Weber, Ursula D.
Zapatka, Marc
Koenig, Rainer
Beroukhim, Rameen
Bergthold, Guillaume
van Sluis, Peter
Volckmann, Richard
Koster, Jan
Versteeg, Rogier
Schmidt, Sabine
Wolf, Stephan
Lawerenz, Chris
Bartholomae, Cynthia C.
von Kalle, Christof
Unterberg, Andreas
Herold-Mende, Christel
Hofer, Silvia
Kulozik, Andreas E.
von Deimling, Andreas
Scheurlen, Wolfram
Felsberg, Joerg
Reifenberger, Guido
Hasselblatt, Martin
Crawford, John R.
Grant, Gerald A.
Jabado, Nada
Perry, Arie
Cowdrey, Cynthia
Croul, Sydney
Zadeh, Gelareh
Korbel, Jan O.
Doz, Francois
Delattre, Olivier
Bader, Gary D.
McCabe, Martin G.
Collins, V. Peter
Kieran, Mark W.
Cho, Yoon-Jae
Pomeroy, Scott L.
Witt, Olaf
Brors, Benedikt
Taylor, Michael D.
Schueller, Ulrich
Korshunov, Andrey
Eils, Roland
Wechsler-Reya, Robert J.
Lichter, Peter
Pfister, Stefan M.
CA ICGC PedBrain Tumor Project
TI Genome Sequencing of SHH Medulloblastoma Predicts Genotype-Related
Response to Smoothened Inhibition
SO CANCER CELL
LA English
DT Article
ID TERT PROMOTER MUTATIONS; HEDGEHOG PATHWAY INHIBITOR; PEDIATRIC
MEDULLOBLASTOMA; NERVOUS-SYSTEM; MOUSE MODELS; CANCER; GROWTH; TUMORS;
ADULT; ITRACONAZOLE
AB Smoothened (SMO) inhibitors recently entered clinical trials for sonic-hedgehog-driven medulloblastoma (SHH-MB). Clinical response is highly variable. To understand the mechanism(s) of primary resistance and identify pathways cooperating with aberrant SHH signaling, we sequenced and profiled a large cohort of SHH-MBs (n = 133). SHH pathway mutations involved PTCH1 (across all age groups), SUFU (infants, including germline), and SMO (adults). Children >3 years old harbored an excess of downstream MYCN and GLI2 amplifications and frequent TP53 mutations, often in the gernnline, all of which were rare in infants and adults. Functional assays in different SHH-MB xenograft models demonstrated that SHH-MBs harboring a PTCH1 mutation were responsive to SMO inhibition, whereas tumors harboring an SUFU mutation or MYCN amplification were primarily resistant.
C1 [Kool, Marcel; Jones, David T. W.; Northcott, Paul A.; Sturm, Dominik; Pfaff, Elke; Stark, Sebastian; Hutter, Sonja; Seker-Cin, Huriye; Johann, Pascal; Bender, Sebastian; Schmidt, Christin; Sieber, Laura; Wittmann, Andrea; Linke, Linda; Witt, Hendrik; Korshunov, Andrey; Pfister, Stefan M.] German Canc Res Ctr, Div Pediat Neurooncol, D-69121 Heidelberg, Germany.
[Jaeger, Natalie; Piro, Rosario M.; Koenig, Rainer; Brors, Benedikt; Eils, Roland] German Canc Res Ctr, Div Theoret Bioinformat, D-69121 Heidelberg, Germany.
[Pugh, Trevor J.; Beroukhim, Rameen; Bergthold, Guillaume] Broad Inst MIT & Harvard, Cambridge, MA 02141 USA.
[Hovestadt, Volker; Weber, Ursula D.; Zapatka, Marc; Lichter, Peter] German Canc Res Ctr, Div Mol Genet, D-69121 Heidelberg, Germany.
[Esparza, L. Adriana; Markant, Shirley L.; Wechsler-Reya, Robert J.] Sanford Burnham Med Res Inst, La Jolla, CA 92037 USA.
[Remke, Marc; Shih, David; Taylor, Michael D.] Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON M5G 1L7, Canada.
[Milde, Till; Witt, Hendrik; Kulozik, Andreas E.; Pfister, Stefan M.] Univ Heidelberg Hosp, Dept Pediat Oncol Hematol & Immunol, D-69120 Heidelberg, Germany.
[Bourdeaut, Franck; Doz, Francois; Delattre, Olivier] Inst Curie, F-75005 Paris, France.
[Bourdeaut, Franck; Delattre, Olivier] Inst Curie, INSERM, U830, F-75248 Paris, France.
[Ryzhova, Marina] NN Burdenko Inst Neurosurg, Dept Neuropathol, Moscow 125047, Russia.
[Rausch, Tobias; Korbel, Jan O.] EMBL, D-69117 Heidelberg, Germany.
[Reimand, Jueri; Bader, Gary D.] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada.
[Koenig, Rainer] Jena Univ Hosp, Ctr Sepsis Control & Care, Integrated Res & Treatment Ctr, D-07747 Jena, Germany.
[Koenig, Rainer] HKI, Leibniz Inst Nat Prod Res & Infect Biol, D-07745 Jena, Germany.
[Beroukhim, Rameen; Bergthold, Guillaume] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
[Beroukhim, Rameen] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Beroukhim, Rameen; Pomeroy, Scott L.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Bergthold, Guillaume] Univ Paris 11, Gustave Roussy Canc Inst, CNRS Vectorol & Anticanc Therapeut, UMR 8203, F-94805 Villejuif, France.
[van Sluis, Peter; Volckmann, Richard; Koster, Jan; Versteeg, Rogier] Univ Amsterdam, Acad Med Ctr, Dept Oncogen, NL-1105 AZ Amsterdam, Netherlands.
[Schmidt, Sabine; Wolf, Stephan] German Canc Res Ctr, Genom & Prote Core Facil, D-69121 Heidelberg, Germany.
[Lawerenz, Chris] German Canc Res Ctr, Data Management Facil, D-69121 Heidelberg, Germany.
[Bartholomae, Cynthia C.; von Kalle, Christof; Unterberg, Andreas; Herold-Mende, Christel] German Canc Res Ctr, Div Translat Oncol, D-69121 Heidelberg, Germany.
[Bartholomae, Cynthia C.; von Kalle, Christof; Unterberg, Andreas; Herold-Mende, Christel] Natl Ctr Tumor Dis NCT, D-69121 Heidelberg, Germany.
[Hofer, Silvia] Univ Zurich Hosp, Dept Oncol, CH-8006 Zurich, Switzerland.
[von Deimling, Andreas; Korshunov, Andrey] Heidelberg Univ, Dept Neuropathol, D-69120 Heidelberg, Germany.
[von Deimling, Andreas; Korshunov, Andrey] German Canc Res Ctr, Clin Cooperat Unit Neuropathol, D-69121 Heidelberg, Germany.
[Scheurlen, Wolfram] Nurnberg Childrens Hosp, Cnopfsche Kinderklin, D-90419 Nurnberg, Germany.
[Felsberg, Joerg; Reifenberger, Guido] Univ Dusseldorf, Dept Neuropathol, D-40225 Dusseldorf, Germany.
[Hasselblatt, Martin] Univ Hosp Munster, Inst Neuropathol, D-48149 Munster, Germany.
[Crawford, John R.] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA.
[Crawford, John R.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
[Crawford, John R.] Rady Childrens Hosp, San Diego, CA 92123 USA.
[Grant, Gerald A.] Duke Univ, Med Ctr, Dept Pediat, Div Pediat Hematol Oncol, Durham, NC 27710 USA.
[Grant, Gerald A.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
[Jabado, Nada] McGill Univ, Dept Pediat & Human Genet, Montreal, PQ H3H 1P3, Canada.
[Perry, Arie; Cowdrey, Cynthia] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA.
[Perry, Arie] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
[Cowdrey, Cynthia] Univ Calif San Francisco, Dept Neurol Surg, Brain Tumor Res Ctr, San Francisco, CA 94143 USA.
[Croul, Sydney; Zadeh, Gelareh] Arthur & Sonia Labatt Brain Tumour Res Ctr, Dept Neuropathol, Toronto, ON M5G 1L7, Canada.
[Doz, Francois] Univ Paris 05, F-75006 Paris, France.
[McCabe, Martin G.] Manchester Acad Hlth Sci Ctr, Manchester M13 9NT, Lancs, England.
[Collins, V. Peter] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England.
[Kieran, Mark W.] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Kieran, Mark W.; Pomeroy, Scott L.] Boston Childrens Hosp, Boston, MA 02215 USA.
[Cho, Yoon-Jae] Stanford Univ, Sch Med, Dept Neurol & Neurosurg, Stanford, CA 94305 USA.
[Witt, Olaf] German Canc Res Ctr, CCU Pediat Oncol, D-69121 Heidelberg, Germany.
[Schueller, Ulrich] Univ Munich, Ctr Neuropathol & Prion Res, D-81377 Munich, Germany.
RP Kool, M (reprint author), German Canc Res Ctr, Div Pediat Neurooncol, D-69121 Heidelberg, Germany.
EM m.kool@dkfz.de
RI Korbel, Jan/G-6470-2012; Pfister, Stefan/F-6860-2013; Brors,
Benedikt/E-5620-2013; Kool, Marcel/H-2541-2013; Shih, David/H-3186-2011;
von Deimling, Andreas/F-7774-2013; Milde, Till/L-7755-2015; Witt,
Hendrik/L-7810-2015; McCabe, Martin/P-5896-2015; Eils,
Roland/B-6121-2009
OI Piro, Rosario/0000-0002-3066-7397; Kieran, Mark/0000-0003-2184-7692;
Remke, Marc/0000-0002-9404-9993; Sturm, Dominik/0000-0003-0250-1696;
Hovestadt, Volker/0000-0002-3480-6649; Hasselblatt,
Martin/0000-0003-2707-8484; Rausch, Tobias/0000-0001-5773-5620; Korbel,
Jan/0000-0002-2798-3794; Pfister, Stefan/0000-0002-5447-5322; Jaeger,
Natalie/0000-0002-9589-7580; Brors, Benedikt/0000-0001-5940-3101; Shih,
David/0000-0002-9802-4937; von Deimling, Andreas/0000-0002-5863-540X;
McCabe, Martin/0000-0002-5138-0707; Eils, Roland/0000-0002-0034-4036
FU PedBrain Tumor Project; German Cancer Aid [109252]; German Federal
Ministry of Education and Research (Bundesministerium fur Bildung und
Forschung) [01KU1201A, MedSys 0315416C, NGFNplus 01GS0883]; Dutch Cancer
Foundations KWF [2010-4713]; KIKA; Brain Tumor Charity; Roche; Novartis
FX For technical support and expertise, we thank the people from the DKFZ
Genomics and Proteomics Core Facility, Malaika Knopf from the NCT
Heidelberg, and GATC Biotech AG for sequencing services. This work was
principally supported by the PedBrain Tumor Project
(http://www.pedbraintumor.org) contributing to the International Cancer
Genome Consortium, funded by German Cancer Aid (109252) and by the
German Federal Ministry of Education and Research (Bundesministerium fur
Bildung und Forschung, grant numbers 01KU1201A, MedSys 0315416C, and
NGFNplus 01GS0883). Additional support came from the Dutch Cancer
Foundations KWF (2010-4713) and KIKA (to M.K.), and the Brain Tumor
Charity (to V.P.C.). G.R. received a research grant from Roche and
honoraria for advisory boards from Merck Serono and Roche. R.B. and O.W.
are consultants for and received grant funding from Novartis.
NR 45
TC 134
Z9 138
U1 4
U2 43
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
EI 1878-3686
J9 CANCER CELL
JI Cancer Cell
PD MAR 17
PY 2014
VL 25
IS 3
BP 393
EP 405
DI 10.1016/j.ccr.2014.02.004
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA AD4PQ
UT WOS:000333233400015
PM 24651015
ER
PT J
AU Caravan, P
AF Caravan, Peter
TI Does anybody really know what (correlation) time it is? Designing
Gd(III) complexes for high field, high relaxivity applications
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Caravan, Peter] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Caravan, Peter] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02129 USA.
EM caravan@nmr.mgh.harvard.edu
NR 0
TC 0
Z9 0
U1 2
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 427-INOR
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HZ
UT WOS:000348457601511
ER
PT J
AU Chen, LJ
Yap, JL
Gallagher, C
Walensky, LD
Fletcher, S
AF Chen, Lijia
Yap, Jeremy L.
Gallagher, Catherine
Walensky, Loren D.
Fletcher, Steven
TI Towards novel anti-cancer agents: Tetrahydroquinoline-based
small-molecules as selective Mcl-1 inhibitors
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Chen, Lijia; Yap, Jeremy L.; Fletcher, Steven] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA.
[Gallagher, Catherine; Walensky, Loren D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA.
[Gallagher, Catherine; Walensky, Loren D.] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA 02215 USA.
EM lijiachen@umaryland.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 326-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HZ
UT WOS:000348457602480
ER
PT J
AU Iki, N
Boros, E
Nakamura, M
Shinoda, K
Caravan, P
AF Iki, Nobuhiko
Boros, Eszter
Nakamura, Mami
Shinoda, Kozo
Caravan, Peter
TI Can Gd(3)TCAS(2) be a new motif of contrast agent for MRI? Unexpected
slow water exchange arising from the tri-Gd-III cluster sandwiched by
two TCAS ligands (TCAS = thiacalix[4]arene-p-tetrasulfonate)
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Iki, Nobuhiko; Nakamura, Mami] Tohoku Univ, Grad Sch Environm Studies, Sendai, Miyagi 9808579, Japan.
[Boros, Eszter] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging,Med Sch, Boston, MA 02129 USA.
[Shinoda, Kozo] Tohoku Univ, Inst Multidisciplinary Res Adv Mat, Sendai, Miyagi 9808577, Japan.
EM iki@m.tohoku.ac.jp
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 559-INOR
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HZ
UT WOS:000348457601639
ER
PT J
AU Moore, A
AF Moore, Anna
TI Iron oxide nanoparticles as theranostic agents for siRNA nad microRNA
therapies in cancer
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Moore, Anna] Massachusetts Gen Hosp, Dept Radiol, Charestown, MA 02129 USA.
EM amoore@helix.mgh.harvard.edu
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 812-INOR
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HZ
UT WOS:000348457601874
ER
PT J
AU Pagel, MD
Yoo, B
Hingorani, DV
Daryaei, I
Akhenblit, PJ
AF Pagel, Marty D.
Yoo, Byunghee
Hingorani, Dina V.
Daryaei, Iman
Akhenblit, Paul J.
TI CatalyCEST MRI contrast agents that detect enzyme activities
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Pagel, Marty D.; Hingorani, Dina V.; Daryaei, Iman] Univ Arizona, Tucson, AZ 85719 USA.
[Pagel, Marty D.] Univ Arizona, Tucson, AZ 85724 USA.
[Pagel, Marty D.; Akhenblit, Paul J.] Univ Arizona, Ctr Canc, Tucson, AZ 85724 USA.
[Yoo, Byunghee] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA.
[Yoo, Byunghee] Harvard Univ, Sch Med, Boston, MA 02129 USA.
EM mpagel@u.arizona.edu
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 740-INOR
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HZ
UT WOS:000348457601806
ER
PT J
AU Yap, JL
Chauhan, J
Chen, LJ
Gallagher, C
Walensky, LD
Fletcher, S
AF Yap, Jeremy L.
Chauhan, Jay
Chen, Lijia
Gallagher, Catherine
Walensky, Loren D.
Fletcher, Steven
TI Design, synthesis, and biological evaluation of
1-hydroxy-2-carboxy-substituted arenes as selective inhibitors of the
Mcl-1 oncoprotein
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Yap, Jeremy L.; Chauhan, Jay; Chen, Lijia; Fletcher, Steven] Univ Maryland, Dept Pharmaceut Sci, Baltimore, MD 21201 USA.
[Gallagher, Catherine; Walensky, Loren D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA.
EM jyap001@umaryland.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 329-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HZ
UT WOS:000348457602483
ER
PT J
AU Zhu, J
Caravan, P
AF Zhu, Jiang
Caravan, Peter
TI Hexameric Mn(II)-EDTA complex as MRI contrast agent
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 247th National Spring Meeting of the American-Chemical-Society (ACS)
CY MAR 16-20, 2014
CL Dallas, TX
SP Amer Chem Soc
C1 [Zhu, Jiang; Caravan, Peter] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Massachusetts Gen Hosp, Charlestown, MA 02129 USA.
[Zhu, Jiang] North Sichuan Med Coll, Sichuan Key Lab Med Imaging, Nanchong 637000, Sichuan, Peoples R China.
EM jiangz@nmr.mgh.harvard.edu
NR 0
TC 0
Z9 0
U1 1
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 16
PY 2014
VL 247
MA 576-INOR
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ8HZ
UT WOS:000348457601656
ER
PT J
AU Bigman, CA
AF Bigman, Cabral A.
TI Social Comparison Framing in Health News and Its Effect on Perceptions
of Group Risk
SO HEALTH COMMUNICATION
LA English
DT Article
ID AFRICAN-AMERICAN COMMUNITIES; MEDICAL DECISION-MAKING; COMPARISON
INFORMATION; STD DISPARITIES; GROUP CUES; COMMUNICATION; COVERAGE;
INEQUALITIES; NEWSPAPERS; JUDGMENTS
AB News about health disparities often compares health risks faced by different demographic groups. Does this social comparison produce a contrast effect? It was hypothesized that when two racial groups are compared, people would perceive the relatively more at-risk group to be more, and the less at-risk group to be less, at-risk than if the same risk information was presented without the comparative reference group. Three experiments with Black and White respondents tested effects of intergroup social comparison framing (SCF) on perceptions of risk for sexually transmitted infections and skin cancer. SCF (including one White and two Black disparity frames) did not raise respondents' perceived risk regarding the more at-risk racial group, but consistently lowered respondents' risk ratings for the less at-risk racial group. The finding that the same statistic was perceived differently in comparative and noncomparative contexts underscores the importance of considering effects of communication about disparities.
C1 [Bigman, Cabral A.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Cambridge, MA 02138 USA.
RP Bigman, CA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,LW 601, Boston, MA 02215 USA.
EM Cabral_Bigman-Galimore@dfci.harvard.edu
FU NCI NIH HHS [P20 CA095856, 5P20CA095856]
NR 61
TC 1
Z9 1
U1 2
U2 8
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 1041-0236
EI 1532-7027
J9 HEALTH COMMUN
JI Health Commun.
PD MAR 16
PY 2014
VL 29
IS 3
BP 267
EP 280
DI 10.1080/10410236.2012.745043
PG 14
WC Communication; Health Policy & Services
SC Communication; Health Care Sciences & Services
GA AH2DT
UT WOS:000335931600005
PM 23829419
ER
PT J
AU Tseng, YD
Paciorek, AT
Martin, NE
D'Amico, AV
Cooperberg, MR
Nguyen, PL
AF Tseng, Yolanda D.
Paciorek, Alan T.
Martin, Neil E.
D'Amico, Anthony V.
Cooperberg, Matthew R.
Nguyen, Paul L.
TI Impact of National Guidelines on Brachytherapy Monotherapy Practice
Patterns for Prostate Cancer
SO CANCER
LA English
DT Article
DE brachytherapy; prostate cancer; guidelines; public health policy;
radiotherapy
ID PERMANENT INTERSTITIAL BRACHYTHERAPY; CLINICAL-PRACTICE GUIDELINES; BEAM
RADIATION-THERAPY; UNITED-STATES; AMERICAN BRACHYTHERAPY; RADICAL
PROSTATECTOMY; RADIOTHERAPY; EXPERIENCE; MANAGEMENT; CARCINOMA
AB BACKGROUNDIn 1999 and 2000, 2 national guidelines recommended brachytherapy monotherapy (BT) primarily for treatment of low-risk prostate cancer but not high-risk prostate cancer. This study examined rates of BT use before and after publication of these guidelines, as compared with 4 other treatment options.
METHODSFrom 1990 to 2011, 8128 men with localized prostate cancer ( T3cN0M0) were treated definitively within the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry with 1 of 5 primary treatments: BT, external beam radiotherapy (EBRT), EBRT with androgen deprivation therapy, EBRT+BT, or radical prostatectomy. Men were categorized into low-, intermediate-, and high-risk groups based on the guidelines' risk-group definitions. Within each risk group, logistic regression was used to estimate odds ratios (OR) comparing BT with other treatment options between the 1990-1998 and 1999-2011 periods, adjusting for age, disease characteristics, and clinic type.
RESULTSIn total, 1117 men received BT alone for low- (n=658), intermediate- (n=244), or high-risk disease (n=215). BT comprised 6.1% of all treatments in 1990-1998 versus 16.6% in 1999-2011 (P<.01). The odds of BT use remained increased after adjusting for potential confounders (OR=3.06; P<.001) and was seen among low- (OR=4.52; P<.001), intermediate- (OR=2.67; P<.001), and even high-risk groups (OR=2.11; P<.001).
CONCLUSIONSNational guidelines did not appear to influence practice patterns, as BT monotherapy use increased relative to other treatments from the 1990-1998 to 1999-2011 periods in unfavorable risk groups including men with high-risk prostate cancer. Cancer 2014;120:824-832. (c) 2013 American Cancer Society.
Brachytherapy monotherapy for treatment of localized prostate cancer increased from 1990 through 1998 to 1999 through 2011 among low-, intermediate-, and high-risk patients. This was seen relative to external beam radiotherapy and radical prostatectomy.
C1 [Tseng, Yolanda D.] Harvard Radiat Oncol Program, Boston, MA 02115 USA.
[Paciorek, Alan T.; Cooperberg, Matthew R.] Univ Calif San Francisco, Dept Urol, San Francisco, CA USA.
[Martin, Neil E.; D'Amico, Anthony V.; Nguyen, Paul L.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA.
[Martin, Neil E.; D'Amico, Anthony V.; Nguyen, Paul L.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Tseng, YD (reprint author), Harvard Radiat Oncol Program, 75 Francis St,ASB L2, Boston, MA 02115 USA.
EM ydtseng@partners.org
RI Martin, Neil/E-2193-2014
OI Martin, Neil/0000-0002-8164-8516
FU Prostate Cancer Foundation; Fitz's Cancer Warriors, David and Cynthia
Chapin
FX This work was funded by the Prostate Cancer Foundation, Fitz's Cancer
Warriors, David and Cynthia Chapin, and a grant from an anonymous family
foundation.
NR 32
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD MAR 15
PY 2014
VL 120
IS 6
BP 824
EP 832
DI 10.1002/cncr.28492
PG 9
WC Oncology
SC Oncology
GA AB9UB
UT WOS:000332140100010
PM 24301555
ER
PT J
AU Garrido, MM
Prigerson, HG
AF Garrido, Melissa M.
Prigerson, Holly G.
TI The End-of-Life Experience: Modifiable Predictors of Caregivers'
Bereavement Adjustment
SO CANCER
LA English
DT Article
DE quality of life; end-of-life care; bereavement; depression; regrets
ID MENTAL-HEALTH; FAMILY CAREGIVERS; PALLIATIVE CARE; ADVANCED CANCER;
RISK-FACTORS; DEATH; DEPRESSION; QUESTIONNAIRE; ASSOCIATIONS;
PREFERENCES
AB BACKGROUNDThe objective of the current study was to determine the best set of predictors of psychological disorders, regrets, health-related quality of life, and mental health function among bereaved caregivers of patients with cancer, thereby identifying promising targets for interventions to improve bereavement adjustment.
METHODSCoping with Cancer is a longitudinal study of patients with advanced cancer and their informal caregivers who were enrolled from 2002 to 2008. The main outcome measure was bereavement adjustment of 245 caregivers (eg, depression, anxiety, and regrets) 6 months after the loss of the patient. The Structured Clinical Interview of the Diagnostic and Statistical Manual of Mental Disorders determined whether caregivers met the criteria for major depressive disorder or an anxiety disorder. Changes in health-related quality of life and mental health function from baseline to after the patient's death were assessed with the Medical Outcomes Study Short Form (SF-36).
RESULTSGreater than 50% of the caregivers reported regret about the cancer patient's end-of-life care; better patient quality of death (adjusted odds ratio, 0.77; 95% confidence interval, 0.67-0.88) reduced the risk of bereavement regret. The incidence of major depressive disorder or anxiety among the bereaved caregivers was 12.6% and was less likely for caregivers with better mental health before the loss of the patient (adjusted odds ratio, 0.03; 95% confidence interval, 0.004-0.25). Better patient quality of death also predicted improved caregiver health-related quality of life (adjusted standardized beta, .28; P<.001). The completion of a do-not-resuscitate order was found to be predictive of improved mental health from before the death of the patient to after the death (adjusted standardized beta, .29; P<.001).
CONCLUSIONSReducing caregiver distress, encouraging advance care planning by patients, and improving patients' quality of death appear to be promising targets of interventions to improve caregiver bereavement adjustment. Cancer 2014;120:918-925. (c) 2013 American Cancer Society.
Using prospective data from patients with advanced cancer and their primary informal caregivers, the results of the current study demonstrate that reducing caregiver distress, encouraging advance care planning by patients, and improving patients' quality of death appear to be promising targets of interventions to improve caregiver bereavement adjustment.
C1 [Garrido, Melissa M.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA.
[Garrido, Melissa M.] Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, New York, NY USA.
[Prigerson, Holly G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Psychosocial Epidemiol & Outcomes Res, Boston, MA 02115 USA.
RP Prigerson, HG (reprint author), Dana Farber Canc Inst, Ctr Psychosocial Epidemiol & Outcomes Res, Dana 1134,450 Brookline Ave, Boston, MA 02215 USA.
EM holly_prigerson@dfci.harvard.edu
FU National Institute of Mental Health [MH63892]; National Cancer Institute
[CA106370, CA156732]; Center for Psychosocial Epidemiology and Outcomes
Research at the Dana-Farber Cancer Institute
FX Supported in part by the following grants to Dr. Prigerson: MH63892 from
the National Institute of Mental Health, CA106370 and CA156732 from the
National Cancer Institute, and the Center for Psychosocial Epidemiology
and Outcomes Research at the Dana-Farber Cancer Institute.
NR 38
TC 19
Z9 19
U1 3
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD MAR 15
PY 2014
VL 120
IS 6
BP 918
EP 925
DI 10.1002/cncr.28495
PG 8
WC Oncology
SC Oncology
GA AB9UB
UT WOS:000332140100021
PM 24301644
ER
PT J
AU Liu, LX
Arany, Z
AF Liu, Laura X.
Arany, Zolt
TI Maternal cardiac metabolism in pregnancy
SO CARDIOVASCULAR RESEARCH
LA English
DT Review
DE Pregnancy; Heart; Metabolism; Peripartum cardiomyopathy
ID ACTIVATED PROTEIN-KINASE; ACUTE MYOCARDIAL-INFARCTION; TRANSCRIPTIONAL
COACTIVATOR PGC-1-ALPHA; PROMOTES MITOCHONDRIAL BIOGENESIS; THORACIC
ELECTRICAL BIOIMPEDANCE; LEFT-VENTRICULAR STRUCTURE;
FATTY-ACID-METABOLISM; PERIPARTUM CARDIOMYOPATHY; DIASTOLIC FUNCTION;
BLOOD-PRESSURE
AB Pregnancy causes dramatic physiological changes in the expectant mother. The placenta, mostly foetal in origin, invades maternal uterine tissue early in pregnancy and unleashes a barrage of hormones and other factors. This foetal 'invasion' profoundly reprogrammes maternal physiology, affecting nearly every organ, including the heart and its metabolism. We briefly review here maternal systemic metabolic changes during pregnancy and cardiac metabolism in general. We then discuss changes in cardiac haemodynamic during pregnancy and review what is known about maternal cardiac metabolism during pregnancy. Lastly, we discuss cardiac diseases during pregnancy, including peripartum cardiomyopathy, and the potential contribution of aberrant cardiac metabolism to disease aetiology.
C1 Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA.
Beth Israel Deaconess Med Ctr, Vasc Biol Res Ctr, Boston, MA 02215 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Arany, Z (reprint author), ECLS906 BIDMC,330 Brookline Ave, Boston, MA 02215 USA.
EM zarany@bidmc.harvard.edu
FU National Institute of Aging [F31AG041598]; NIH Heart, Lung, and Blood
Institute; American Heart Association; Ellison Foundation
FX L.L. is supported by the National Institute of Aging (F31AG041598) and
Z.A. is supported by the NIH Heart, Lung, and Blood Institute, the
American Heart Association, and the Ellison Foundation.
NR 118
TC 19
Z9 20
U1 1
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0008-6363
EI 1755-3245
J9 CARDIOVASC RES
JI Cardiovasc. Res.
PD MAR 15
PY 2014
VL 101
IS 4
BP 545
EP 553
DI 10.1093/cvr/cvu009
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AE6LL
UT WOS:000334104300002
PM 24448314
ER
PT J
AU Selvarajah, S
Pyne, S
Chen, E
Sompallae, R
Ligon, AH
Nielsen, GP
Dranoff, G
Stack, E
Loda, M
Flavin, R
AF Selvarajah, Shamini
Pyne, Saumyadipta
Chen, Eleanor
Sompallae, Ramakrishna
Ligon, Azra H.
Nielsen, Gunnlaugur P.
Dranoff, Glenn
Stack, Edward
Loda, Massimo
Flavin, Richard
TI High-Resolution Array CGH and Gene Expression Profiling of Alveolar Soft
Part Sarcoma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID BREAST-CANCER; TRANSCRIPTION FACTOR; PROTEIN EXPRESSION; CELL; FUSION;
ORIGIN; HYPERMETHYLATION; MYOD1; PAX6
AB Purpose: Alveolar soft part sarcoma (ASPS) is a soft tissue sarcoma with poor prognosis, and little molecular evidence exists for its origin, initiation, and progression. The aim of this study was to elucidate candidate molecular pathways involved in tumor pathogenesis.
Experimental Design: We employed high-throughput array comparative genomic hybridization (aCGH) and cDNA-Mediated Annealing, Selection, Ligation, and Extension Assay to profile the genomic and expression signatures of primary and metastatic ASPS from 17 tumors derived from 11 patients. We used an integrative bioinformatics approach to elucidate the molecular pathways associated with ASPS progression. FISH was performed to validate the presence of the t(X;17)(p11.2;q25) ASPL-TFE3 fusion and, hence, confirm the aCGH observations.
Results: FISH analysis identified the ASPL-TFE3 fusion in all cases. aCGH revealed a higher number of numerical aberrations in metastatic tumors relative to primaries, but failed to identify consistent alterations in either group. Gene expression analysis highlighted 1,063 genes that were differentially expressed between the two groups. Gene set enrichment analysis identified 16 enriched gene sets (P < 0.1) associated with differentially expressed genes. Notable among these were several stem cell gene expression signatures and pathways related to differentiation. In particular, the paired box transcription factor PAX6 was upregulated in the primary tumors, along with several genes whose mouse orthologs have previously been implicated in Pax6 DNA binding during neural stem cell differentiation.
Conclusion: In addition to suggesting a tentative neural line of differentiation for ASPS, these results implicate transcriptional deregulation from fusion genes in the pathogenesis of ASPS. (C)2014 AACR.
C1 [Selvarajah, Shamini; Chen, Eleanor; Ligon, Azra H.; Loda, Massimo; Flavin, Richard] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Selvarajah, Shamini; Pyne, Saumyadipta; Ligon, Azra H.; Dranoff, Glenn; Stack, Edward; Loda, Massimo; Flavin, Richard] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA.
[Nielsen, Gunnlaugur P.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Sompallae, Ramakrishna] Univ Iowa, Carver Coll Med, Iowa City, IA USA.
[Flavin, Richard] St James Hosp, Dept Pathol, Dublin 8, Ireland.
RP Flavin, R (reprint author), St James Hosp, Jamess St, Dublin 8, Ireland.
EM flavinrichard@gmail.com
FU iCureASPS; National Cancer Institute [RO1CA131945, PO1CA89021, P50
CA90381]
FX Funding for this work was obtained from iCureASPS and a gift from Nuclea
Biomarkers to the Jimmy Fund and the Loda laboratory. This work was also
supported in part by the National Cancer Institute (RO1CA131945,
PO1CA89021, and P50 CA90381) to M. Loda.
NR 32
TC 8
Z9 9
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2014
VL 20
IS 6
BP 1521
EP 1530
DI 10.1158/1078-0432.CCR-13-2090
PG 10
WC Oncology
SC Oncology
GA AE2ON
UT WOS:000333812700015
PM 24493828
ER
PT J
AU Garcia-Gomez, A
Quwaider, D
Canavese, M
Ocio, EM
Tian, Z
Blanco, JF
Berger, AJ
Ortiz-de-Solorzano, C
Hernandez-Iglesias, T
Martens, ACM
Groen, RWJ
Mateo-Urdiales, J
Fraile, S
Galarraga, M
Chauhan, D
Miguel, JFS
Raje, N
Garayoa, M
AF Garcia-Gomez, Antonio
Quwaider, Dalia
Canavese, Miriam
Ocio, Enrique M.
Tian, Ze
Blanco, Juan F.
Berger, Allison J.
Ortiz-de-Solorzano, Carlos
Hernandez-Iglesias, Teresa
Martens, Anton C. M.
Groen, Richard W. J.
Mateo-Urdiales, Joaquin
Fraile, Susana
Galarraga, Miguel
Chauhan, Dharminder
San Miguel, Jesus F.
Raje, Noopur
Garayoa, Mercedes
TI Preclinical Activity of the Oral Proteasome Inhibitor MLN9708 in Myeloma
Bone Disease
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID MULTIPLE-MYELOMA; OSTEOBLAST DIFFERENTIATION; IN-VIVO;
ANTITUMOR-ACTIVITY; BORTEZOMIB; CELLS; MODELS; WNT; OSTEOCLASTOGENESIS;
BISPHOSPHONATES
AB Purpose: MLN9708 (ixazomib citrate), which hydrolyzes to pharmacologically active MLN2238 (ixazomib), is a next-generation proteasome inhibitor with demonstrated preclinical and clinical antimyeloma activity, but yet with an unknown effect on myeloma bone disease. Here, we investigated its bone anabolic and antiresorptive effects in the myeloma setting and in comparison with bortezomib in preclinical models.
Experimental Design: The in vitro effect of MLN2238 was tested on osteoclasts and osteoclast precursors from healthy donors and patients with myeloma, and on osteoprogenitors derived from bone marrow mesenchymal stem cells also from both origins. We used an in vivo model of bone marrow-disseminated human myeloma to evaluate MLN2238 antimyeloma and bone activities.
Results: Clinically achievable concentrations of MLN2238 markedly inhibited in vitro osteoclastogenesis and osteoclast resorption; these effects involved blockade of RANKL (receptor activator of NF-kB ligand)-induced NF-kB activation, F-actin ring disruption, and diminished expression of alpha V beta 3 integrin. A similar range of MLN2238 concentrations promoted in vitro osteoblastogenesis and osteoblast activity (even in osteoprogenitors from patients with myeloma), partly mediated by activation of TCF/beta-catenin signaling and upregulation of the IRE1 component of the unfolded protein response. In a mouse model of bone marrow-disseminated human multiple myeloma, orally administered MLN2238 was equally effective as bortezomib to control tumor burden and also provided a marked benefit in associated bone disease (sustained by both bone anabolic and anticatabolic activities).
Conclusion: Given favorable data on pharmacologic properties and emerging clinical safety profile of MLN9708, it is conceivable that this proteasome inhibitor may achieve bone beneficial effects in addition to its antimyeloma activity in patients with myeloma. (C)2014 AACR.
C1 [Garcia-Gomez, Antonio; Quwaider, Dalia; Ocio, Enrique M.; Hernandez-Iglesias, Teresa; Fraile, Susana; San Miguel, Jesus F.; Garayoa, Mercedes] Univ Salamanca, CSIC, IBMCC, Ctr Invest Canc, Salamanca 37007, Spain.
[Garcia-Gomez, Antonio; San Miguel, Jesus F.; Garayoa, Mercedes] Ctr Red Med Regenerat & Terapia Celular Castilla, Salamanca, Spain.
[Garcia-Gomez, Antonio; Ocio, Enrique M.; Blanco, Juan F.; San Miguel, Jesus F.; Garayoa, Mercedes] Hosp Univ Salamanca IBSAL, Salamanca, Spain.
[Ortiz-de-Solorzano, Carlos; Mateo-Urdiales, Joaquin; Galarraga, Miguel] Univ Navarra, Lab Imagen Canc, Ctr Invest Med Aplicada, E-31080 Pamplona, Spain.
[Canavese, Miriam; Raje, Noopur] Harvard Univ, Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA USA.
[Tian, Ze; Chauhan, Dharminder] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Berger, Allison J.] Millennium Pharmaceut Inc, Cambridge, MA USA.
[Martens, Anton C. M.; Groen, Richard W. J.] Univ Med Ctr Utrecht, Dept Cell Biol, Utrecht, Netherlands.
[Martens, Anton C. M.] Univ Med Ctr Utrecht, Dept Immunol, Utrecht, Netherlands.
RP Garcia-Gomez, A (reprint author), Univ Salamanca, CSIC, IBMCC, Ctr Invest Canc, Campus Miguel de Unamuno,Avda Univ Coimbra S-N, Salamanca 37007, Spain.
EM agargo@usal.es
RI Ortiz de Solorzano, Carlos/G-3278-2010;
OI Ortiz de Solorzano, Carlos/0000-0001-8720-0205; SAN MIGUEL,
JESUS/0000-0002-9183-4857; Groen, Richard/0000-0002-5010-4604
FU Spanish MICINN-ISCIII [PI081825, PI1202591]; Centro en Red of
Regenerative Medicine and Cellular Therapy from Castilla and Leon; RTICC
Hematology Program [RD12/0036/0058]; Spanish FIS [PS09/01897]; MINECO
[DPI2012-38090-C03-02]; CIMA; Spanish Society of Hematology and
Hemotherapy
FX This work was supported by grants from the Spanish MICINN-ISCIII
(PI081825; PI1202591), Centro en Red of Regenerative Medicine and
Cellular Therapy from Castilla and Leon, RTICC Hematology Program
(RD12/0036/0058), Spanish FIS (PS09/01897), MINECO DPI2012-38090-C03-02,
and CIMA (The "UTE project CIMA"). A. Garcia-Gomez was supported by the
"Spanish Society of Hematology and Hemotherapy."
NR 49
TC 22
Z9 22
U1 1
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2014
VL 20
IS 6
BP 1542
EP 1554
DI 10.1158/1078-0432.CCR-13-1657
PG 13
WC Oncology
SC Oncology
GA AE2ON
UT WOS:000333812700017
PM 24486586
ER
PT J
AU Godbersen, JC
Humphries, LA
Danilova, OV
Kebbekus, PE
Brown, JR
Eastman, A
Danilov, AV
AF Godbersen, J. Claire
Humphries, Leigh Ann
Danilova, Olga V.
Kebbekus, Peter E.
Brown, Jennifer R.
Eastman, Alan
Danilov, Alexey V.
TI The Nedd8-Activating Enzyme Inhibitor MLN4924 Thwarts
Microenvironment-Driven NF-kappa B Activation and Induces Apoptosis in
Chronic Lymphocytic Leukemia B Cells
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID RECEPTOR SIGNALING PATHWAY; THERAPEUTIC TARGET; NOXA/MCL-1 BALANCE;
IN-VIVO; EXPRESSION; SURVIVAL; RESISTANCE; PROLIFERATION; KINASE; BIM
AB Background: Stromal-mediated signaling enhances NF-kappa B pathway activity in chronic lymphocytic leukemia (CLL) B cells, leading to cell survival and chemoresistance. Ubiquitination of I kappa B alpha may partially account for constitutive activation of NF-kappa B. MLN4924 is an investigational agent that inhibits the Nedd8-activating enzyme, thereby neutralizing Cullin-RING ubiquitin ligases and preventing degradation of their substrates.
Experimental Design: We conducted a preclinical assessment of MLN4924 in CLL. Primary CLL cells were cocultured in vitro with CD40L-expressing stroma to mimic the prosurvival conditions present in lymphoid tissue. The effect of MLN4924 on CLL cell apoptosis, NF-kappa B pathway activity, Bcl-2 family members, and cell cycle was assessed by flow cytometry, Western blotting, PCR, and immunocytochemistry.
Results: CD40L-expressing stroma protected CLL cells from spontaneous apoptosis and induced resistance to multiple drugs, accompanied by NF-kappa B activation and Bim repression. Treatment with MLN4924 induced CLL cell apoptosis and circumvented stroma-mediated resistance. This was accompanied by accumulation of phospho-I kappa B alpha, decreased nuclear translocation of p65 and p52 leading to inhibition of both the canonical and noncanonical NF-kappa B pathways, and reduced transcription of their target genes, notably chemokines. MLN4924 promoted induction of Bim and Noxa in the CLL cells leading to rebalancing of Bcl-2 family members toward the proapoptotic BH3-only proteins. siRNA-mediated knockdown of Bim or Noxa decreased sensitivity to MLN4924. MLN4924 enhanced the antitumor activity of the inhibitors of B-cell receptor (BCR)-associated kinases.
Conclusions: MLN4924 disrupts NF-kappa B activation and induces Bim expression in CLL cells, thereby preventing stroma-mediated resistance. Our data provide rationale for further evaluation of MLN4924 in CLL. (C)2014 AACR.
C1 [Godbersen, J. Claire; Humphries, Leigh Ann; Kebbekus, Peter E.; Danilov, Alexey V.] Dartmouth Hitchcock Med Ctr, Dept Med, Lebanon, NH 03766 USA.
[Danilova, Olga V.] Dartmouth Hitchcock Med Ctr, Dept Pathol, Lebanon, NH 03766 USA.
[Eastman, Alan] Geisel Sch Med Dartmouth, Dept Pharmacol & Toxicol, Hanover, NH USA.
[Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Danilov, AV (reprint author), Norris Cotton Canc Ctr, 1 Med Ctr Dr, Lebanon, NH 03766 USA.
EM Alexey.V.Danilov@hitchcock.org
FU National Cancer Institute [3P30CA023108-31S4]; Leukemia & Lymphoma
Society; American Cancer Society
FX Support to A.V. Danilov is provided by a National Cancer Institute new
faculty award (3P30CA023108-31S4) to the Norris Cotton Cancer Center. A.
Eastman and A.V. Danilov are supported by a translational research award
from the Leukemia & Lymphoma Society. J.R. Brown is supported by the
Leukemia and Lymphoma Society and the American Cancer Society and is a
Scholar in Clinical Research of the Leukemia and Lymphoma Society.
NR 50
TC 29
Z9 29
U1 1
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2014
VL 20
IS 6
BP 1576
EP 1589
DI 10.1158/1078-0432.CCR-13-0987
PG 14
WC Oncology
SC Oncology
GA AE2ON
UT WOS:000333812700020
PM 24634471
ER
PT J
AU Oxnard, GR
Paweletz, CP
Kuang, YA
Mach, SL
O'Connell, A
Messineo, MM
Luke, JJ
Butaney, M
Kirschmeier, P
Jackman, DM
Janne, PA
AF Oxnard, Geoffrey R.
Paweletz, Cloud P.
Kuang, Yanan
Mach, Stacy L.
O'Connell, Allison
Messineo, Melissa M.
Luke, Jason J.
Butaney, Mohit
Kirschmeier, Paul
Jackman, David M.
Janne, Pasi A.
TI Noninvasive Detection of Response and Resistance in EGFR-Mutant Lung
Cancer Using Quantitative Next-Generation Genotyping of Cell-Free Plasma
DNA
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; METASTATIC BREAST-CANCER; ACQUIRED-RESISTANCE;
KRAS MUTATIONS; DIGITAL PCR; COLORECTAL-CANCER; GEFITINIB; THERAPY;
ADENOCARCINOMAS; INHIBITION
AB Purpose: Tumor genotyping using cell-free plasma DNA (cfDNA) has the potential to allow noninvasive assessment of tumor biology, yet many existing assays are cumbersome and vulnerable to false-positive results. We sought to determine whether droplet digital PCR (ddPCR) of cfDNA would allow highly specific and quantitative assessment of tumor genotype.
Experimental Design: ddPCR assays for EGFR, KRAS, and BRAF mutations were developed using plasma collected from patients with advanced lung cancer or melanoma of a known tumor genotype. Sensitivity and specificity were determined using cancers with nonoverlapping genotypes as positive and negative controls. Serial assessment of response and resistance was studied in patients with EGFR-mutant lung cancer on a prospective trial of erlotinib.
Results: We identified a reference range for EGFR L858R and exon 19 deletions in specimens from KRAS-mutant lung cancer, allowing identification of candidate thresholds with high sensitivity and 100% specificity. Received operative characteristic curve analysis of four assays demonstrated an area under the curve in the range of 0.80 to 0.94. Sensitivity improved in specimens with optimal cfDNA concentrations. Serial plasma genotyping of EGFR-mutant lung cancer on erlotinib demonstrated pretreatment detection of EGFR mutations, complete plasma response in most cases, and increasing levels of EGFR T790M emerging before objective progression.
Conclusions: Noninvasive genotyping of cfDNA using ddPCR demonstrates assay qualities that could allow effective translation into a clinical diagnostic. Serial quantification of plasma genotype allows noninvasive assessment of response and resistance, including detection of resistance mutations up to 16 weeks before radiographic progression.
C1 [Oxnard, Geoffrey R.; Paweletz, Cloud P.; Kuang, Yanan; Mach, Stacy L.; O'Connell, Allison; Messineo, Melissa M.; Luke, Jason J.; Butaney, Mohit; Kirschmeier, Paul; Jackman, David M.; Janne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Paweletz, Cloud P.; Kuang, Yanan; O'Connell, Allison; Messineo, Melissa M.; Kirschmeier, Paul; Janne, Pasi A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02215 USA.
[Oxnard, Geoffrey R.; Luke, Jason J.; Jackman, David M.; Janne, Pasi A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Luke, Jason J.; Jackman, David M.; Janne, Pasi A.] Harvard Univ, Sch Med, Boston, MA USA.
RP Oxnard, GR (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Dana 1234, Boston, MA 02215 USA.
EM Geoffrey_Oxnard@DFCI.Harvard.edu
FU National Cancer Institute at the NIH [R01-CA135257, P50-CA090578];
Conquer Cancer Foundation of ASCO (Career Development Award); Genentech
FX This work was supported in part by the National Cancer Institute at the
NIH (R01-CA135257, P50-CA090578), the Conquer Cancer Foundation of ASCO
(Career Development Award), and research funding from Genentech.
NR 31
TC 171
Z9 183
U1 4
U2 36
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 15
PY 2014
VL 20
IS 6
BP 1698
EP 1705
DI 10.1158/1078-0432.CCR-13-2482
PG 8
WC Oncology
SC Oncology
GA AE2ON
UT WOS:000333812700031
PM 24429876
ER
PT J
AU Bell, ME
Street, AE
Stafford, J
AF Bell, Margret E.
Street, Amy E.
Stafford, Jane
TI Victims' Psychosocial Well-Being After Reporting Sexual Harassment in
the Military
SO JOURNAL OF TRAUMA & DISSOCIATION
LA English
DT Article
DE reporting; military; sexual assault; sexual harassment
ID RESPONSES; RAPE; EXPERIENCES; VETERANS; OUTCOMES; ASSAULT; SYSTEMS;
WOMEN; LEGAL
AB Given the importance of reporting to sexual harassment prevention and intervention efforts, it is not surprising that an extensive scientific literature has developed on predictors of victims' decisions about making a formal report to authorities about their experiences. In contrast, little empirical work has focused on how reporting affects victims, particularly their psychosocial well-being. This study used a national sample of 1,562 former military Reservists who had experienced sexual harassment during their service to examine the relationship between reporting; experiences reporting; and psychosocial well-being, as indicated by post-harassment functioning, worst symptoms of posttraumatic stress disorder (PTSD) following the harassment, and current symptoms of depression. Making a formal report was not associated with well-being, but among those who did report, perceiving that the report had resulted in the harassment being addressed by authorities was associated with better post-harassment functioning and fewer symptoms of PTSD. Satisfaction with the reporting process showed the strongest association with well-being, demonstrating small but meaningful associations with depression and medium-to-large and medium associations with post-harassment functioning and PTSD, respectively. Although findings did not vary by gender, predictors accounted for more variance in well-being for men than women. In the whole sample, satisfaction with the reporting process mediated the relationship between victims' perceptions of system responsiveness to the report and post-harassment functioning and PTSD. Findings suggest that a victim's perceptions of and satisfaction with the reporting process may impact well-being more strongly than whether the victim made a report to authorities. Men may be even more strongly impacted by their experiences with the reporting process than women
C1 VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Boston, MA 02130 USA.
Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA.
RP Bell, ME (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div 116B 3, 150 South Huntington Ave, Boston, MA 02130 USA.
EM margret.bell@va.gov
NR 29
TC 5
Z9 5
U1 2
U2 15
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 1529-9732
EI 1529-9740
J9 J TRAUMA DISSOCIATIO
JI J. Trauma Dissociation
PD MAR 15
PY 2014
VL 15
IS 2
BP 133
EP 152
DI 10.1080/15299732.2014.867563
PG 20
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA AE4WT
UT WOS:000333987700002
PM 24410254
ER
PT J
AU Shimony, A
Afilalo, J
Flynn, AW
Langleben, D
Agnihotri, AK
Morin, JF
Shahian, DM
Picard, MH
Rudski, LG
AF Shimony, Avi
Afilalo, Jonathan
Flynn, Aidan W.
Langleben, David
Agnihotri, Arvin K.
Morin, Jean-Francois
Shahian, David M.
Picard, Michael H.
Rudski, Lawrence G.
TI Usefulness of Right Ventricular Dysfunction to Predict New-Onset Atrial
Fibrillation Following Coronary Artery Bypass Grafting
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID CARDIAC-SURGERY; ECHOCARDIOGRAPHIC-ASSESSMENT; EUROPEAN-ASSOCIATION;
CLINICAL IMPORTANCE; AMERICAN-SOCIETY; RISK; RECOMMENDATIONS; IMPACT;
MECHANISMS; PATHOPHYSIOLOGY
AB Postoperative atrial fibrillation (AF) is a serious yet common complication after coronary artery bypass grafting (CABG) surgery. Risk factors for postoperative AF have been identified, including echocardiographic parameters, and these are relied on to implement preventative strategies that reduce the incidence of AF. There has yet to be a study examining the impact of echocardiographic right-sided cardiac parameters on the prediction of postoperative AF. Thus, a panel of right-sided cardiac parameters was measured in a cohort of patients undergoing isolated CABG surgery, excluding those who did not have echocardiographic assessment within 30 days before surgery and those with any history of AF. The primary outcome was postoperative AF defined as any episode of AF requiring treatment during the index hospitalization. Postoperative AF occurred in 197 of 768 patients (25.6%); these were older and more likely to have hypertension and chronic kidney disease. After adjustment for clinical and echocardiographic variables, left atrial volume index >= 34 ml/m(2) (odds ratio [OR] 1.98, 95% confidence interval [CI] 1.36 to 2.87), abnormal right ventricular myocardial performance index (OR 1.50, 95% CI 1.01 to 2.24), and advancing age (OR 1.05, 95% CI 1.03 to 1.07) were found to be independent predictors of postoperative AF. In conclusion, right ventricular myocardial performance index is a novel predictor of postoperative AF in patients undergoing isolated CABG surgery and appears to be additive to established risk factors such as age and left atrial volume. (c) 2014 Elsevier Inc. All rights reserved.
C1 [Shimony, Avi; Afilalo, Jonathan; Langleben, David; Rudski, Lawrence G.] McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Div Cardiol, Montreal, PQ H3T 1E2, Canada.
[Morin, Jean-Francois] McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Div Cardiac Surg, Montreal, PQ H3T 1E2, Canada.
[Afilalo, Jonathan; Flynn, Aidan W.; Picard, Michael H.] Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Cardiac Ultrasound Lab, Boston, MA 02115 USA.
[Agnihotri, Arvin K.; Shahian, David M.] Harvard Univ, Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02115 USA.
[Shahian, David M.] Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA.
[Shahian, David M.] Harvard Univ, Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02115 USA.
RP Rudski, LG (reprint author), McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Div Cardiol, Montreal, PQ H3T 1E2, Canada.
EM lrudski@jgh.mcgill.ca
OI Picard, Michael/0000-0002-9264-3243
FU Azrieli Foundation grant through the Jewish General Hospital Foundation,
Montreal, Quebec, Canada
FX Dr. Avi Shimony was supported by a Azrieli Foundation grant through the
Jewish General Hospital Foundation, Montreal, Quebec, Canada. The other
authors have no conflicts of interest to disclose.
NR 30
TC 7
Z9 8
U1 0
U2 2
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
EI 1879-1913
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD MAR 15
PY 2014
VL 113
IS 6
BP 913
EP 918
DI 10.1016/j.amjcard.2013.11.048
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AD7WD
UT WOS:000333476700002
PM 24440329
ER
PT J
AU Feemster, LC
Au, DH
AF Feemster, Laura C.
Au, David H.
TI Penalizing Hospitals for Chronic Obstructive Pulmonary Disease
Readmissions
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE quality indicators; chronic obstructive pulmonary disease; patient
readmission; Medicate
ID MEDICARE BENEFICIARIES; ACUTE EXACERBATIONS; HEALTH OUTCOMES; INPATIENT
CARE; QUALITY; PROGRAM; RATES; REHOSPITALIZATION; HOSPITALIZATIONS;
ASSOCIATION
AB In October 2014, the U.S. Centers for Medicare and Medicaid Services (CMS) Will expand its Hospital Readmission Reduction Program (HRRP) to include chronic obstructive pulinonary disease (COPD). Under the new policy, hospitals with high risk-adjusted, 30-day all-cause unplanned readmission rates after an index hospitalization for a COPD exacerbation will be penalized with reduced reimbursement for the treatment of Medicare beneficiaries. In this perspective, we review the history of the HRRP, including the recent addition of COPD to the policy. We critically assess the use of 30-day all-cause COPD readmissions as an accountability measure, discussing potential benefits and then highlighting the substantial drawbacks and potential unintended consequences of the measure that could adversely affect providers, hospitals, and patients with COPD. We conclude by emphasizing the need to place the 30-day COPD readmission measure in the context of a reconceived model for postdischarge quality and review several frameworks that could help guide this process.
C1 [Feemster, Laura C.; Au, David H.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA.
[Feemster, Laura C.; Au, David H.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA.
RP Feemster, LC (reprint author), 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA.
EM lcecere@uw.edu
FU National Heart, Lung, and Blood Institute, National Institutes of Health
[K23HL111116]; VA Puget Sound Health Care System; Health Services
Research and Developmen
FX Supported by a National Heart, Lung, and Blood Institute, National
Institutes of Health, K23 Award K23HL111116 (L.C.F.) and the VA Puget
Sound Health Care System, Health Services Research and Development
(LCF., D.H.A.).
NR 36
TC 20
Z9 20
U1 1
U2 6
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD MAR 15
PY 2014
VL 189
IS 6
BP 634
EP 639
DI 10.1164/rccm.201308-1541PP
PG 6
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA AD6OQ
UT WOS:000333381100007
PM 24460431
ER
PT J
AU de los Heros, P
Alessi, DR
Gourlay, R
Campbell, DG
Deak, M
Macartney, TJ
Kahle, KT
Zhang, JW
AF de los Heros, Paola
Alessi, Dario R.
Gourlay, Robert
Campbell, David G.
Deak, Maria
Macartney, Thomas J.
Kahle, Kristopher T.
Zhang, Jinwei
TI The WNK-regulated SPAK/OSR1 kinases directly phosphorylate and inhibit
the K+-Cl- co-transporters
SO BIOCHEMICAL JOURNAL
LA English
DT Article
DE gamma-aminobutyric acid (GABA); blood pressure/hypertension; ion
homoeostasis; K+-Cl- co-transporter 2 (KCC2); K+-Cl- co-transporter 3
(KCC3); Na+-Cl- co-transporter (NCC); Na+-K+-2Cl(-) co-transporter 1
(NKCC1); protein kinase; signal transduction
ID CATION-CHLORIDE COTRANSPORTERS; ALANINE-RICH KINASE; BLOOD-PRESSURE;
MOLECULAR PHYSIOLOGY; PROTEIN-KINASES; CELL-VOLUME; HYPOKALEMIC
ALKALOSIS; BARTTERS-SYNDROME; SALT TRANSPORT; ION-TRANSPORT
AB Precise homoeostasis of the intracellular concentration of Cl- is achieved via the co-ordinated activities of the Cl- influx and efflux. We demonstrate that the WNK (WNK lysine-deficient protein kinase)-activated SPAK (SPS1-related proline/alanine-rich kinase)/OSR1 (oxidative stress-responsive kinase 1) known to directly phosphorylate and stimulate the N[K]CCs (Na+-K+ ion co-transporters), also promote inhibition of the KCCs (K+-Cl- co-transporters) by directly phosphorylating a recently described C-terminal threonine residue conserved in all KCC isoforms [Site-2 (Thr(1048))]. First, we demonstrate that SPAK and OSR1, in the presence of the MO25 regulatory subunit, robustly phosphorylates all KCC isoforms at Site-2 in vitro. Secondly, STOCK1S-50699, a WNK pathway inhibitor, suppresses SPAK/OSR1 activation and KCC3A Site-2 phosphorylation with similar efficiency. Thirdly, in ES (embryonic stem) cells lacking SPAK/OSR1 activity, endogenous phosphorylation of KCC isoforms at Site-2 is abolished and these cells display elevated basal activity of Rb-86(+) uptake that was not markedly stimulated further by hypotonic high K+ conditions, consistent with KCC3A activation. Fourthly, a tight correlation exists between SPAK/OSR1 activity and the magnitude of KCC3A Site-2 phosphorylation. Lastly, a Site-2 alanine KCC3A mutant preventing SPAK/OSR1 phosphorylation exhibits increased activity. We also observe that KCCs are directly phosphorylated by SPAK/OSR1, at a novel Site-3 (Thr(5) in KCC1/KCC3 and Thr(6) in KCC2/KCC4), and a previously recognized KCC3-specific residue, Site-4 (Ser(96)). These data demonstrate that the WNK-regulated SPAK/OSR1 kinases directly phosphorylate the N[K]CCs and KCCs, promoting their stimulation and inhibition respectively. Given these reciprocal actions with anticipated net effects of increasing Cl- influx, we propose that the targeting of WNK-SPAK/OSR1 with kinase inhibitors might be a novel potent strategy to enhance cellular Cl- extrusion, with potential implications for the therapeutic modulation of epithelial and neuronal ion transport in human disease states.
C1 [de los Heros, Paola; Alessi, Dario R.; Gourlay, Robert; Campbell, David G.; Deak, Maria; Macartney, Thomas J.; Zhang, Jinwei] Univ Dundee, Coll Life Sci, MRC, Prot Phosphorylat & Ubiguitylat Unit, Dundee DD1 5EH, Scotland.
[Kahle, Kristopher T.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
[Kahle, Kristopher T.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Kahle, Kristopher T.] Childrens Hosp Boston, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA.
RP Alessi, DR (reprint author), Univ Dundee, Coll Life Sci, MRC, Prot Phosphorylat & Ubiguitylat Unit, Dow St, Dundee DD1 5EH, Scotland.
RI Campbell, David/K-1874-2015;
OI Campbell, David/0000-0003-2278-2149; Alessi, Dario/0000-0002-2140-9185;
Zhang, Jinwei/0000-0001-8683-509X
FU Medical Research Council; Wellcome Trust [091415]; Manton Center for
Orphan Diseases at Children's Hospital Boston at Harvard Medical School;
Harvard /MIT Joint Research Grants Program in Basic Neuroscience;
AstraZeneca; Boehringer-Ingelheim; GlaxoSmithKline; Merck KgaA; Janssen
Pharmaceutica; Pfizer
FX This work was supported by the Medical Research Council and the Wellcome
Trust [grant number 091415] as well as the pharmaceutical companies
supporting the Division of Signal Transduction Therapy Unit
(AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck KgaA, Janssen
Pharmaceutica and Pfizer). K.T.K. is supported by the Manton Center for
Orphan Diseases at Children's Hospital Boston at Harvard Medical School,
and the Harvard /MIT Joint Research Grants Program in Basic
Neuroscience.
NR 57
TC 34
Z9 34
U1 0
U2 8
PU PORTLAND PRESS LTD
PI LONDON
PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND
SN 0264-6021
EI 1470-8728
J9 BIOCHEM J
JI Biochem. J.
PD MAR 15
PY 2014
VL 458
BP 559
EP 573
DI 10.1042/BJ20131478
PN 3
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AE1GT
UT WOS:000333718500013
PM 24393035
ER
PT J
AU Ali, OA
Verbeke, C
Johnson, C
Sands, RW
Lewin, SA
White, D
Doherty, E
Dranoff, G
Mooney, DJ
AF Ali, Omar A.
Verbeke, Catia
Johnson, Chris
Sands, R. Warren
Lewin, Sarah A.
White, Des
Doherty, Edward
Dranoff, Glenn
Mooney, David J.
TI Identification of Immune Factors Regulating Antitumor Immunity Using
Polymeric Vaccines with Multiple Adjuvants
SO CANCER RESEARCH
LA English
DT Article
ID DENDRITIC-CELL SUBSETS; TUMOR-NECROSIS-FACTOR; T-CELL; IN-VIVO;
CANCER-IMMUNOTHERAPY; INNATE IMMUNITY; ANTIGEN; DIFFERENTIATION;
INTERFERON; INTERLEUKIN-12
AB The innate cellular and molecular components required to mediate effective vaccination against weak tumor-associated antigens remain unclear. In this study, we used polymeric cancer vaccines incorporating different classes of adjuvants to induce tumor protection, to identify dendritic cell (DC) subsets and cytokines critical to this efficacy. Three-dimensional, porous polymer matrices loaded with tumor lysates and presenting distinct combinations of granulocyte macrophage colony-stimulating factor (GM-CSF) and various Toll-like receptor (TLR) agonists affected 70% to 90% prophylactic tumor protection in B16-F10 melanoma models. In aggressive, therapeutic B16 models, the vaccine systems incorporating GM-CSF in combination with P(I: C) or CpG-ODN induced the complete regression of solid tumors (<= 40 mm(2)), resulting in 33% long-term survival. Regression analysis revealed that the numbers of vaccine-resident CD8(+) DCs, plasmacytoid DCs (pDC), along with local interleukin (IL)-12, and granulocyte colony-stimulating factor (G-CSF) concentrations correlated strongly to vaccine efficacy regardless of adjuvant type. Furthermore, vaccine studies in Batf3(-/-) mice revealed that CD8(+) DCs are required to affect tumor protection, as vaccines in these mice were deficient in cytotoxic T lymphocytes priming and IL-12 induction in comparison with wild-type. These studies broadly demonstrate that three-dimensional polymeric vaccines provide a potent platform for prophylactic and therapeutic protection, and can be used as a tool to identify critical components of a desired immune response. Specifically, these results suggest that CD8(+) DCs, pDCs, IL-12, and G-CSF play important roles in priming effective antitumor responses with these vaccines. (C) 2014 AACR.
C1 [Ali, Omar A.; Verbeke, Catia; Johnson, Chris; Sands, R. Warren; Lewin, Sarah A.; White, Des; Doherty, Edward; Mooney, David J.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.
[Dranoff, Glenn] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med Oncol,Dana Farber Canc Inst, Boston, MA USA.
[Dranoff, Glenn] Harvard Univ, Sch Med, Brigham & Womens Hosp, Canc Vaccine Ctr,Dana Farber Canc Inst, Boston, MA USA.
[Dranoff, Glenn] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA.
[Ali, Omar A.; Verbeke, Catia; Sands, R. Warren; Mooney, David J.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
RP Mooney, DJ (reprint author), Harvard Univ, Sch Engn & Appl Sci, 29 Oxford St,319 Pierce Hall, Cambridge, MA 02138 USA.
EM mooneyd@seas.harvard.edu
FU NIBIB NIH HHS [R01 EB015498]
NR 47
TC 22
Z9 22
U1 3
U2 24
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 MAR 15
PY 2014
VL 74
IS 6
BP 1670
EP 1681
DI 10.1158/0008-5472.CAN-13-0777
PG 12
WC Oncology
SC Oncology
GA AE2OD
UT WOS:000333811700007
PM 24480625
ER
PT J
AU Steinert, G
Scholch, S
Niemietz, T
Iwata, N
Garcia, SA
Behrens, B
Voigt, A
Kloor, M
Benner, A
Bork, U
Rahbari, NN
Buchler, MW
Stoecklein, NH
Weitz, J
Koch, M
AF Steinert, Gunnar
Schoelch, Sebastian
Niemietz, Thomas
Iwata, Naoki
Garcia, Sebastian A.
Behrens, Bianca
Voigt, Anita
Kloor, Matthias
Benner, Axel
Bork, Ulrich
Rahbari, Nuh N.
Buechler, Markus W.
Stoecklein, Nikolas H.
Weitz, Juergen
Koch, Moritz
TI Immune Escape and Survival Mechanisms in Circulating Tumor Cells of
Colorectal Cancer
SO CANCER RESEARCH
LA English
DT Article
ID COMPARATIVE GENOMIC HYBRIDIZATION; INTEGRIN-ASSOCIATED PROTEIN;
NON-HODGKIN-LYMPHOMA; BREAST-CANCER; BONE-MARROW; MICROSATELLITE
INSTABILITY; MICROMETASTATIC CELLS; LIVER METASTASES; GENETIC-ANALYSIS;
SINGLE CELLS
AB The prognosis of colorectal cancer is closely linked to the occurrence of distant metastases. Systemic dissemination is most likely caused by circulating tumor cells (CTC). Despite the fundamental role of CTC within the metastatic cascade, technical obstacles have so far prevented detailed genomic and, in particular, phenotypic analyses of CTC, which may provide molecular targets to delay or prevent distant metastases. We show here a detailed genomic analysis of single colorectal cancer-derived CTC by array comparative genomic hybridization (aCGH), mutational profiling, and microsatellite instability (MSI) analysis. Furthermore, we report the first gene expression analysis of manually selected colorectal cancer-derived CTC by quantitative real-time PCR (qRT-PCR) to investigate transcriptional changes, enabling CTC to survive in circulation and form distant metastases. aCGH confirmed the tumor cell identity of CellSearch-isolated colorectal cancer-derived CTC. Mutational and MSI analyses revealed mutational profiles of CTC to be similar, but not identical to the corresponding tumor tissue. Several CTC exhibited mutations in key genes such as KRAS or TP53 that could not be detected in the tumor. Gene expression analyses revealed both a pronounced upregulation of CD47 as a potential immune-escape mechanism and a significant downregulation of several other pathways, suggesting a dormant state of viable CTC. Our results suggest mutational heterogeneity between tumor tissue and CTC that should be considered in future trials on targeted therapy and monitoring of response. The finding of upregulated immune-escape pathways, which may be responsible for survival of CTC in circulation, could provide a promising target to disrupt the metastatic cascade in colorectal cancer. (C) 2014 AACR.
C1 [Steinert, Gunnar; Niemietz, Thomas; Iwata, Naoki; Buechler, Markus W.] Heidelberg Univ, Inst Pathol, Dept Gen Gastrointestinal & Transplant Surg, Heidelberg, Germany.
[Voigt, Anita] Heidelberg Univ, Inst Pathol, Dept Appl Tumor Biol, Heidelberg, Germany.
[Benner, Axel] German Canc Res Ctr, Div Biostat, Heidelberg, Germany.
[Schoelch, Sebastian; Garcia, Sebastian A.; Bork, Ulrich; Weitz, Juergen; Koch, Moritz] Tech Univ Dresden, Med Fak Carl Gustav Carus, Dept Gastrointestinal Thorac & Vasc Surg, D-01307 Dresden, Germany.
[Behrens, Bianca; Stoecklein, Nikolas H.] Univ Dusseldorf, Fac Med, Univ Hosp, Dept Gen Visceral & Paediat Surg, Dusseldorf, Germany.
[Rahbari, Nuh N.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA.
[Rahbari, Nuh N.] Harvard Univ, Sch Med, Boston, MA USA.
RP Koch, M (reprint author), Tech Univ Dresden, Med Fak Carl Gustav Carus, Dept Gastrointestinal Thorac & Vasc Surg, Fetscherstr 74, D-01307 Dresden, Germany.
EM moritz.koch@uniklinikum-dresden.de
OI Voigt, Anita Yvonne/0000-0002-6794-0385; Scholch,
Sebastian/0000-0003-0012-3177
FU Deutsche Forschungsgemeinschaft (DFG) [WE 3548/4-1/2, KFO 227]
FX This work was supported by the KFO 227 program (Clinical Research Group
227: Colorectal cancer: from primary tumor progression towards
metastases (WE 3548/4-1/2) of Deutsche Forschungsgemeinschaft (DFG).
NR 54
TC 49
Z9 51
U1 1
U2 26
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 MAR 15
PY 2014
VL 74
IS 6
BP 1694
EP 1704
DI 10.1158/0008-5472.CAN-13-1885
PG 11
WC Oncology
SC Oncology
GA AE2OD
UT WOS:000333811700009
PM 24599131
ER
PT J
AU Zhao, JJ
Lin, JH
Zhu, D
Wang, XJ
Brooks, D
Chen, M
Chu, ZB
Takada, K
Ciccarelli, B
Admin, S
Tao, JG
Tai, YT
Treon, S
Pinkus, G
Kuo, WP
Hideshima, T
Bouxsein, M
Munshi, N
Anderson, K
Carrasco, R
AF Zhao, Jian-Jun
Lin, Jianhong
Zhu, Di
Wang, Xujun
Brooks, Daniel
Chen, Ming
Chu, Zhang-Bo
Takada, Kohichi
Ciccarelli, Bryan
Admin, Samir
Tao, Jianguo
Tai, Yu-Tzu
Treon, Steven
Pinkus, Geraldine
Kuo, Winston Patrick
Hideshima, Teru
Bouxsein, Mary
Munshi, Nikhil
Anderson, Kenneth
Carrasco, Ruben
TI miR-30-5p Functions as a Tumor Suppressor and Novel Therapeutic Tool by
Targeting the Oncogenic Wnt/beta-Catenin/BCL9 Pathway
SO CANCER RESEARCH
LA English
DT Article
ID MULTIPLE-MYELOMA; IN-VITRO; MOLECULAR-ORIGINS; DOWN-REGULATION;
BETA-CATENIN; STEM-CELLS; CANCER; EXPRESSION; MICRORNAS; DISEASE
AB Wnt/beta-catenin signaling underlies the pathogenesis of a broad range of human cancers, including the deadly plasma cell cancer multiple myeloma. In this study, we report that downregulation of the tumor suppressor microRNA miR-30-5p is a frequent pathogenetic event in multiple myeloma. Evidence was developed that miR-30-5p downregulation occurs as a result of interaction between multiple myeloma cells and bone marrow stromal cells, which in turn enhances expression of BCL9, a transcriptional coactivator of the Wnt signaling pathway known to promote multiple myeloma cell proliferation, survival, migration, drug resistance, and formation of multiple myeloma cancer stem cells. The potential for clinical translation of strategies to re-express miR-30-5p as a therapeutic approach was further encouraged by the capacity of miR-30c and miR-30 mix to reduce tumor burden and metastatic potential in vivo in three murine xenograft models of human multiple myeloma without adversely affecting associated bone disease. Together, our findings offer a preclinical rationale to explore miR-30-5p delivery as an effective therapeutic strategy to eradicate multiple myeloma cells in vivo. (C) 2014 AACR.
C1 [Zhao, Jian-Jun; Lin, Jianhong; Zhu, Di; Chen, Ming; Chu, Zhang-Bo; Takada, Kohichi; Ciccarelli, Bryan; Tai, Yu-Tzu; Treon, Steven; Hideshima, Teru; Munshi, Nikhil; Anderson, Kenneth; Carrasco, Ruben] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Lin, Jianhong; Tai, Yu-Tzu; Hideshima, Teru; Munshi, Nikhil; Anderson, Kenneth] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA.
[Admin, Samir] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Pinkus, Geraldine; Carrasco, Ruben] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Kuo, Winston Patrick] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA.
[Brooks, Daniel; Bouxsein, Mary] Beth Israel Deaconess Med Ctr, Ctr Adv Orthopaed Studies, Boston, MA 02215 USA.
[Tao, Jianguo] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Wang, Xujun] Tongji Univ, Sch Life Sci & Technol, Jerome Lipper Multiple Myeloma Ctr, Shanghai 200092, Peoples R China.
RP Carrasco, R (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA.
EM ruben_carrasco@dfci.harvard.edu
FU Multiple Myeloma Research Foundation (MMRF); SPORE in Multiple Myeloma
Career Development Award; China Scholarship Council (CSC); Harvard
Catalyst, The Harvard Clinical and Translational Science Center; MMRF
[1R01CA151391]
FX J.-J. Zhao was supported by a Multiple Myeloma Research Foundation
(MMRF) research fellow award. J. Lin was supported by a SPORE in
Multiple Myeloma Career Development Award. Z.-B. Chu was supported by a
China Scholarship Council (CSC) award. W. P. Kuo was supported by
Harvard Catalyst, The Harvard Clinical and Translational Science Center.
K. Anderson is an American Cancer Society Clinical Research Professor.
R. Carrasco is supported by an MMRF senior award and a 1R01CA151391.
NR 45
TC 43
Z9 48
U1 1
U2 10
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 MAR 15
PY 2014
VL 74
IS 6
BP 1801
EP 1813
DI 10.1158/0008-5472.CAN-13-3311-T
PG 13
WC Oncology
SC Oncology
GA AE2OD
UT WOS:000333811700018
PM 24599134
ER
PT J
AU Hong, J
Yuan, YF
Wang, JP
Liao, YD
Zou, RH
Zhu, CL
Li, BK
Liang, Y
Huang, PZ
Wang, ZW
Lin, WY
Zeng, YX
Dai, JL
Chung, RT
AF Hong, Jian
Yuan, Yunfei
Wang, Jianping
Liao, Yadi
Zou, Ruhai
Zhu, Chuanlong
Li, Binkui
Liang, Yi
Huang, Pinzhu
Wang, Zongwei
Lin, Wenyu
Zeng, Yixin
Dai, Jia Le
Chung, Raymond T.
TI Expression of Variant Isoforms of the Tyrosine Kinase SYK Determines the
Prognosis of Hepatocellular Carcinoma
SO CANCER RESEARCH
LA English
DT Article
ID TUMOR-SUPPRESSOR GENE; BREAST-CANCER CELLS; EPITHELIAL-MESENCHYMAL
TRANSITION; POOR-PROGNOSIS; LUNG-CANCER; GROWTH; PROGRESSION;
INHIBITION; STRATEGY; MOTILITY
AB The spleen tyrosine kinase (SYK) has been reported as a novel biomarker for human hepatocellular carcinoma, but the functional contributions of its two isoforms SYK(L) and SYK(S) are undefined. In this study, we investigated their biologic functions and possible prognostic values in hepatocellular carcinoma. SYK(L) was downregulated in 38% of human specimens of hepatocellular carcinoma examined, whereas SYK(S) was detectable in 40% of these specimens but not in normal liver tissue samples without cirrhosis. SYK(S) expression correlated with pathologic parameters characteristic of tumor metastasis, including multiple tumors (P = 0.003) and vascular invasion (P = 0.001). Further, SYK(S) was specifically associated with epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma specimens. Functional studies showed that SYK(S) promoted tumor growth, suppressed apoptosis, and induced EMT through the extracellular signal-regulated kinase pathway, countering the opposite effects of SYK(L). Patients with SYK(L+/S-) tumors exhibited longer overall survival and time to recurrence than those with SYK(L-/S-) or SYK(L+/S+) tumors (P < 0.001). Taken together, our findings showed that SYK(S) enhances invasion, whereas SYK(L) inhibits metastasis in hepatocellular carcinoma. We suggest that SYK(L) downregulation or SYK(S) elevation are strong predictors of poor survival in patients with hepatocellular carcinoma, indicative of a need for aggressive therapeutic intervention. (C) 2014 AACR.
C1 [Hong, Jian; Yuan, Yunfei; Liao, Yadi; Zou, Ruhai; Li, Binkui; Liang, Yi; Huang, Pinzhu; Zeng, Yixin] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Guangzhou 510060, Guangdong, Peoples R China.
[Hong, Jian; Yuan, Yunfei; Liao, Yadi; Li, Binkui] Sun Yat Sen Univ, Ctr Canc, Dept Hepatobiliary Oncol, Guangzhou 510060, Guangdong, Peoples R China.
[Wang, Jianping] Sun Yat Sen Univ, Affiliated Hosp 6, Dept Surg, Guangzhou 510060, Guangdong, Peoples R China.
[Hong, Jian; Zhu, Chuanlong; Wang, Zongwei; Lin, Wenyu; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA USA.
[Dai, Jia Le] Univ Texas MD Anderson Canc Ctr, Div Pharma, Houston, TX 77030 USA.
RP Yuan, YF (reprint author), Sun Yat Sen Univ, Ctr Canc, Guangzhou 510060, Guangdong, Peoples R China.
EM yuanyf@mail.sysu.edu.cn; rtchung@partners.org
FU National Natural Science Foundation of China [81201634, 81172344,
81101863]; Natural Science Foundation of Guangdong Province of China
[S2011040004570]; NIH [DK078772]
FX This study was supported by the National Natural Science Foundation of
China (81201634, 81172344, and 81101863), the Natural Science Foundation
of Guangdong Province of China (S2011040004570), and NIH grant DK078772
(RTC).
NR 39
TC 11
Z9 11
U1 3
U2 11
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 MAR 15
PY 2014
VL 74
IS 6
BP 1845
EP 1856
DI 10.1158/0008-5472.CAN-13-2104
PG 12
WC Oncology
SC Oncology
GA AE2OD
UT WOS:000333811700022
PM 24477596
ER
PT J
AU Ruff, CT
Giugliano, RP
Braunwald, E
Hoffman, EB
Deenadayalu, N
Ezekowitz, MD
Camm, AJ
Weitz, JI
Lewis, BS
Parkhomenko, A
Yamashita, T
Antman, EM
AF Ruff, Christian T.
Giugliano, Robert P.
Braunwald, Eugene
Hoffman, Elaine B.
Deenadayalu, Naveen
Ezekowitz, Michael D.
Camm, A. John
Weitz, Jeffrey I.
Lewis, Basil S.
Parkhomenko, Alexander
Yamashita, Takeshi
Antman, Elliott M.
TI Comparison of the efficacy and safety of new oral anticoagulants with
warfarin in patients with atrial fibrillation: a meta-analysis of
randomised trials
SO LANCET
LA English
DT Article
ID RE-LY TRIAL; NORMALIZED RATIO CONTROL; STROKE PREVENTION; RISK-FACTORS;
SUBGROUP ANALYSIS; DABIGATRAN; THERAPY; RIVAROXABAN; APIXABAN;
THROMBOEMBOLISM
AB Background Four new oral anticoagulants compare favourably with warfarin for stroke prevention in patients with atrial fibrillation; however, the balance between efficacy and safety in subgroups needs better definition. We aimed to assess the relative benefit of new oral anticoagulants in key subgroups, and the effects on important secondary outcomes.
Methods We searched Medline from Jan 1, 2009, to Nov 19, 2013, limiting searches to phase 3, randomised trials of patients with atrial fibrillation who were randomised to receive new oral anticoagulants or warfarin, and trials in which both efficacy and safety outcomes were reported. We did a prespecified meta-analysis of all 71 683 participants included in the RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF-TIMI 48 trials. The main outcomes were stroke and systemic embolic events, ischaemic stroke, haemorrhagic stroke, all-cause mortality, myocardial infarction, major bleeding, intracranial haemorrhage, and gastrointestinal bleeding. We calculated relative risks (RRs) and 95% CIs for each outcome. We did subgroup analyses to assess whether differences in patient and trial characteristics affected outcomes. We used a random-effects model to compare pooled outcomes and tested for heterogeneity.
Findings 42 411 participants received a new oral anticoagulant and 29 272 participants received warfarin. New oral anticoagulants significantly reduced stroke or systemic embolic events by 19% compared with warfarin (RR 0.81, 95% CI 0.73-0.91; p<0.0001), mainly driven by a reduction in haemorrhagic stroke (0.49, 0.38-0.64; p<0.0001). New oral anticoagulants also significantly reduced all-cause mortality (0.90, 0.85-0.95; p=0.0003) and intracranial haemorrhage (0.48, 0.39-0.59; p<0.0001), but increased gastrointestinal bleeding (1.25, 1.01-1.55; p= 0.04). We noted no heterogeneity for stroke or systemic embolic events in important subgroups, but there was a greater relative reduction in major bleeding with new oral anticoagulants when the centre-based time in therapeutic range was less than 66% than when it was 66% or more (0.69, 0.59-0.81 vs 0.93, 0.76-1.13; p for interaction 0.022). Low-dose new oral anticoagulant regimens showed similar overall reductions in stroke or systemic embolic events to warfarin (1.03, 0.84-1.27; p= 0.74), and a more favourable bleeding profile (0.65, 0.43-1.00; p= 0.05), but significantly more ischaemic strokes (1.28, 1.02-1.60; p= 0.045).
Interpretation This meta-analysis is the first to include data for all four new oral anticoagulants studied in the pivotal phase 3 clinical trials for stroke prevention or systemic embolic events in patients with atrial fibrillation. New oral anticoagulants had a favourable risk-benefit profile, with significant reductions in stroke, intracranial haemorrhage, and mortality, and with similar major bleeding as for warfarin, but increased gastrointestinal bleeding. The relative efficacy and safety of new oral anticoagulants was consistent across a wide range of patients. Our findings off er clinicians a more comprehensive picture of the new oral anticoagulants as a therapeutic option to reduce the risk of stroke in this patient population.
C1 [Ruff, Christian T.; Giugliano, Robert P.; Braunwald, Eugene; Hoffman, Elaine B.; Deenadayalu, Naveen; Antman, Elliott M.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Ruff, Christian T.; Giugliano, Robert P.; Braunwald, Eugene; Hoffman, Elaine B.; Deenadayalu, Naveen; Antman, Elliott M.] Harvard Univ, Sch Med, Boston, MA USA.
[Ezekowitz, Michael D.] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA.
[Ezekowitz, Michael D.] Cardiovasc Res Fdn, New York, NY USA.
[Camm, A. John] St Georges Univ, London, England.
[Weitz, Jeffrey I.] McMaster Univ, Hamilton, ON, Canada.
[Weitz, Jeffrey I.] Thrombosis & Atherosclerosis Res Inst, Hamilton, ON, Canada.
[Lewis, Basil S.] Lady Davis Carmel Med Ctr, Haifa, Israel.
[Parkhomenko, Alexander] ND Strazhesko Cardiol Res Inst, Kiev, Ukraine.
[Yamashita, Takeshi] Cardiovasc Inst, Tokyo, Japan.
RP Ruff, CT (reprint author), Thrombolysis Myocardial Infarct TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA.
EM cruff@partners.org
FU Daiichi Sankyo; Johnson Johnson; Merck; Duke University; AstraZeneca;
Merck Co; Sanofi - Aventis; GlaxoSmith Kline; Bristol-Myers Squibb;
Beckman Coulter; Roche Diagnostics; Pfizer; Genyzme; Amorcyte; Medicines
Co; CardioRentis; CVRx; Eli Lilly; Menarini International; Medscape;
Bayer; Boehringer Ingelheim
FX CTR has served as a consultant and has received honoraria from Daiichi
Sankyo, Boehringer Ingelheim, and Bristol-Myers Squibb. RPG has served
as a consultant and has received honoraria from Bristol-Myers Squibb,
Janssen, Daiichi Sankyo, Merck, Sanofi, and is a member of the TIMI
Study Group, which has received research grant support from Daiichi
Sankyo, Johnson & Johnson, and Merck. EB has recieved grants and
personal fees for lectures from Daiichi Sankyo; grants from Duke
University, AstraZeneca, Johnson & Johnson, Merck & Co, Sanofi -
Aventis, GlaxoSmith Kline, Bristol-Myers Squibb, Beckman Coulter, Roche
Diagnostics, and Pfizer; uncompensated personal fees for consultancy
from Merck & Co; personal fees for consultancies from Genyzme, Amorcyte,
Medicines Co, CardioRentis, and Sanofi - Aventis; uncompensated personal
fees for lectures from Merck and CVRx; and personal fees for lectures
from Eli Lilly, Menarini International, Medscape, and Bayer outside the
submitted work. MDE has served as a consultant and has received
honoraria from Boehringer Ingelheim, Bayer, Johnson & Johnson, Janssen,
Bristol-Myers Squibb, Pfizer, Daiichi Sankyo, Sanofi, Portola,
Medtronics, Aegerion, Merck, Gilead, and Pozen. AJC has served as a
consultant and has received honoraria from Boehringer Ingelheim, Bayer,
Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo. JIW has served as a
consultant and has received honoraria from Boehringer Ingelheim, Bayer,
Janssen, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo. BSL has
served as a consultant to Bayer, Bristol-Myers Squibb, and Pfizer and
received research grants in these trials from Boehringer Ingelheim,
Bayer, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo. AP has received
a research grant from Daiichi Sankyo, Boehringer Ingelheim, Bayer,
Bristol-Myers Squibb. TY has received honoraria from Boehringer
Ingelheim, Bayer, Bristol-Myers Squibb, Pfi zer, and Daiichi Sankyo. EMA
has received a research grant from Daiichi Sankyo. All other authors
declare that they have no conflicts of interest.
NR 40
TC 666
Z9 694
U1 26
U2 139
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD MAR 15
PY 2014
VL 383
IS 9921
BP 955
EP 962
DI 10.1016/S0140-6736(13)62343-0
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA AD8MR
UT WOS:000333520700026
PM 24315724
ER
PT J
AU Mahmood, SS
Levy, D
Vasan, RS
Wang, TJ
AF Mahmood, Syed S.
Levy, Daniel
Vasan, Ramachandran S.
Wang, Thomas J.
TI The Framingham Heart Study and the epidemiology of cardiovascular
disease: a historical perspective
SO LANCET
LA English
DT Review
ID ISOLATED SYSTOLIC HYPERTENSION; POPULATION-BASED COHORT;
ATRIAL-FIBRILLATION; RISK-FACTORS; FOLLOW-UP; MYOCARDIAL-INFARCTION;
DIABETES-MELLITUS; NATURAL-HISTORY; BLOOD PRESSURE; FAILURE
AB On Sept 29, 2013, the Framingham Heart Study will celebrate 65 years since the examination of the first volunteer in 1948. During this period, the study has provided substantial insight into the epidemiology and risk factors of cardiovascular disease. The origins of the study are closely linked to the cardiovascular health of President Franklin D Roosevelt and his premature death from hypertensive heart disease and stroke in 1945. In this Review we describe the events leading to the foundation of the Framingham Heart Study, and provide a brief historical overview of selected contributions from the study.
C1 [Mahmood, Syed S.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA.
[Levy, Daniel; Vasan, Ramachandran S.; Wang, Thomas J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Levy, Daniel] NHLBI, Populat Res Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Wang, Thomas J.] Vanderbilt Univ, Div Cardiovasc Med, Nashville, TN 37235 USA.
RP Wang, TJ (reprint author), Vanderbilt Univ Sch Med, Div Cardiovasc Med, Nashville, TN 37232 USA.
EM thomas.j.wang@vanderbilt.edu
OI Mahmood, Syed Saad/0000-0001-6938-1321; Ramachandran,
Vasan/0000-0001-7357-5970
FU NIH [N01-HC-25195]
FX We thank Paul Sorlie (National Heart, Lung, and Blood Institute,
Bethesda, MD, USA) for his assistance in granting access to the
Framingham Archives. We thank Gerald Oppenheimer (Department of
Sociomedical Sciences, Columbia University, New York, NY, USA) for
comments on the history of the Framingham Heart Study. This work was
supported by NIH contract N01-HC-25195.
NR 81
TC 79
Z9 86
U1 8
U2 36
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD MAR 15
PY 2014
VL 383
IS 9921
BP 999
EP 1008
DI 10.1016/S0140-6736(13)61752-3
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA AD8MR
UT WOS:000333520700030
PM 24084292
ER
PT J
AU Klein, OJ
Jung, YK
Evans, CL
AF Klein, O. J.
Jung, Y. K.
Evans, C. L.
TI Longitudinal, quantitative monitoring of therapeutic response in 3D in
vitro tumor models with OCT for high-content therapeutic screening
SO METHODS
LA English
DT Article
DE 3D in vitro models; Optical coherence tomography; Time-lapse; Overlay
culture; Image analysis; Therapeutic response
ID OPTICAL COHERENCE TOMOGRAPHY; CANCER BIOLOGY; GROWTH; CULTURE;
CYTOTOXICITY; APOPTOSIS; EFFICACY; CELLS; PDT
AB In vitro three-dimensional models of cancer have the ability to recapitulate many features of tumors found in vivo, including cell-cell and cell-matrix interactions, microenvironments that become hypoxic and acidic, and other barriers to effective therapy. These model tumors can be large, highly complex, heterogeneous, and undergo time-dependent growth and treatment response processes that are difficult to track and quantify using standard imaging tools. Optical coherence tomography is an optical ranging technique that is ideally suited for visualizing, monitoring, and quantifying the growth and treatment response dynamics occurring in these informative model systems. By optimizing both optical coherence tomography and 3D culture systems, it is possible to continuously and non-perturbatively monitor advanced in vitro models without the use of labels over the course of hours and days. In this chapter, we describe approaches and methods for creating and carrying out quantitative therapeutic screens with in vitro 3D cultures using optical coherence tomography to gain insights into therapeutic mechanisms and build more effective treatment regimens. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Klein, O. J.; Jung, Y. K.; Evans, C. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA.
RP Evans, CL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, CNY 3214,13th St, Charlestown, MA 02129 USA.
EM oklein@partners.org; jung.yookyung@mgh.harvar-d.edu;
evans.conor@mgh.harvard.edu
FU National Institutes of Health (NIH) Innovative Molecular Analysis
Technologies (IMAT) program [R21 CA155535]; NIH [DP2 OD007096]
FX The authors would like to acknowledge the members of Evans group for
their assistance in editing this manuscript. This research was support
by the National Institutes of Health (NIH) Innovative Molecular Analysis
Technologies (IMAT) program, grant number R21 CA155535, and the NIH
Director's New Innovator Award, grant number DP2 OD007096. Information
on the New Innovator Award Program is at
http://nihroadmap.nih.gov/newinnovator/.
NR 32
TC 4
Z9 4
U1 0
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-2023
EI 1095-9130
J9 METHODS
JI Methods
PD MAR 15
PY 2014
VL 66
IS 2
BP 299
EP 311
DI 10.1016/j.ymeth.2013.08.028
PG 13
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AE1ZM
UT WOS:000333773100021
PM 24013042
ER
PT J
AU Kang, HK
Cypel, Y
Kilbourne, AM
Magruder, KM
Serpi, T
Collins, JF
Frayne, SM
Furey, J
Huang, GD
Kimerling, R
Reinhard, MJ
Schumacher, K
Spiro, A
AF Kang, Han K.
Cypel, Yasmin
Kilbourne, Amy M.
Magruder, Kathy M.
Serpi, Tracey
Collins, Joseph F.
Frayne, Susan M.
Furey, Joan
Huang, Grant D.
Kimerling, Rachel
Reinhard, Matthew J.
Schumacher, Karen
Spiro, Avron, III
TI HealthViEWS: Mortality Study of Female US Vietnam Era Veterans,
1965-2010
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE HealthViEWS; mortality; veterans; Vietnam; women
ID UNITED-STATES-ARMY; CANCER MORTALITY; PROPORTIONATE MORTALITY;
POSTSERVICE MORTALITY; REGISTERED NURSES; MILITARY SERVICE; LUNG-CANCER;
FOLLOW-UP; DEATH; WOMEN
AB We conducted a retrospective study among 4,734 women who served in the US military in Vietnam (Vietnam cohort), 2,062 women who served in countries near Vietnam (near-Vietnam cohort), and 5,313 nondeployed US military women (US cohort) to evaluate the associations of mortality outcomes with Vietnam War service. Veterans were identified from military records and followed for 40 years through December 31, 2010. Information on underlying causes of death was obtained from death certificates and the National Death Index. Based on 2,743 deaths, all 3 veteran cohorts had lower mortality risk from all causes combined and from several major causes, such as diabetes mellitus, heart disease, chronic obstructive pulmonary disease, and nervous system disease relative to comparable US women. However, excess deaths from motor vehicle accidents were observed in the Vietnam cohort (standardized mortality ratio = 3.67, 95% confidence interval (CI): 2.30, 5.56) and in the US cohort (standardized mortality ratio = 1.91, 95% CI: 1.02, 3.27). More than two-thirds of women in the study were military nurses. Nurses in the Vietnam cohort had a 2-fold higher risk of pancreatic cancer death (adjusted relative risk = 2.07, 95% CI: 1.00, 4.25) and an almost 5-fold higher risk of brain cancer death compared with nurses in the US cohort (adjusted relative risk = 4.61, 95% CI: 1.27, 16.83). Findings of all-cause and motor vehicle accident deaths among female Vietnam veterans were consistent with patterns of postwar mortality risk among other war veterans.
C1 [Kang, Han K.; Cypel, Yasmin] US Dept Vet Affairs, Off Publ Hlth, Postdeployment Hlth Grp, Washington, DC 20420 USA.
[Kilbourne, Amy M.; Schumacher, Karen] Vet Affairs Ann Arbor Ctr Clin Management Res, Ann Arbor, MI USA.
[Kilbourne, Amy M.] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA.
[Magruder, Kathy M.] Med Univ S Carolina, Dept Psychiat, Mental Hlth Serv, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA.
[Serpi, Tracey; Collins, Joseph F.] Vet Affairs Maryland Hlth Care Syst, Cooperat Studies Program Coordinating Ctr, Perry Point, MD USA.
[Frayne, Susan M.; Kimerling, Rachel] Vet Affairs Palo Alto Hlth Care Syst, Vet Affairs Hlth Serv Res & Dev Ctr Innovat Imple, Palo Alto, CA USA.
[Frayne, Susan M.] Stanford Univ, Sch Med, Div Gen Med Disciplines, Palo Alto, CA 94304 USA.
[Furey, Joan] US Dept Vet Affairs, Ctr Women Vet, Washington, DC 20420 USA.
[Huang, Grant D.] US Dept Vet Affairs, Cooperat Studies Program, Cent Off, Off Res & Dev, Washington, DC 20420 USA.
[Kimerling, Rachel] Natl Ctr Postttraumat Stress Disorder, Palo Alto, CA USA.
[Reinhard, Matthew J.] DC Vet Affairs Med Ctr, War Related Illness & Injury Study Ctr, Washington, DC USA.
[Reinhard, Matthew J.] Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC USA.
[Spiro, Avron, III] Vet Affairs Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA.
[Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Spiro, Avron, III] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA.
RP Cypel, Y (reprint author), US Dept Vet Affairs, Program Epidemiol, Postdeployment Hlth Strateg Healthcare Grp 10P3A, Off Publ Hlth, Washington, DC 20420 USA.
EM yasmin.cypel@va.gov
FU Department of Veterans Affairs, Veterans Health Administration, Office
of Research and Development, Cooperative Studies Program
FX This work was supported by the Department of Veterans Affairs, Veterans
Health Administration, Office of Research and Development, Cooperative
Studies Program.
NR 53
TC 9
Z9 9
U1 1
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD MAR 15
PY 2014
VL 179
IS 6
BP 721
EP 730
DI 10.1093/aje/kwt319
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AD4UP
UT WOS:000333246800009
PM 24488510
ER
PT J
AU Yeh, YC
Blouin, GC
Reddy, P
AF Yeh, Yu-Chen
Blouin, Gayle C.
Reddy, Prabashni
TI Evidence to support use of palonosetron over generic serotonin type
3-receptor antagonists for chemotherapy-induced nausea and vomiting
SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY
LA English
DT Editorial Material
ID MODERATELY EMETOGENIC CHEMOTHERAPY; PHASE-III; GUIDELINE UPDATE;
DOUBLE-BLIND; PREVENTION; ONDANSETRON; EFFICACY; TRIAL; METAANALYSIS
C1 [Yeh, Yu-Chen; Reddy, Prabashni] Partners Healthcare, Ctr Drug Policy, Needham, MA USA.
[Blouin, Gayle C.] Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA.
RP Yeh, YC (reprint author), Partners Healthcare, Ctr Drug Policy, Needham, MA USA.
EM yyeh@partners.org
NR 40
TC 2
Z9 2
U1 0
U2 1
PU AMER SOC HEALTH-SYSTEM PHARMACISTS
PI BETHESDA
PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA
SN 1079-2082
EI 1535-2900
J9 AM J HEALTH-SYST PH
JI Am. J. Health-Syst. Pharm.
PD MAR 15
PY 2014
VL 71
IS 6
BP 500
EP 506
DI 10.2146/ajhp130394
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AD6OL
UT WOS:000333380500010
PM 24589541
ER
PT J
AU Downey, LA
Loftis, JM
AF Downey, Luke A.
Loftis, Jennifer M.
TI Altered energy production, lowered antioxidant potential, and
inflammatory processes mediate CNS damage associated with abuse of the
psychostimulants MDMA and methamphetamine
SO EUROPEAN JOURNAL OF PHARMACOLOGY
LA English
DT Review
DE Methamphetamine; 3,4-Methylenedioxy-N-methylamphetamine (MDMA);
Neurodegenerative diseases; Inflammation; Oxidative stress;
Bioenergetics
ID OXIDATIVE STRESS; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; ECSTASY USERS;
RAT-BRAIN; POSITRON EMISSION; USE DISORDERS; NEUROTOXICITY; IMPAIRMENT;
GLUCOSE; DOPAMINE
AB Central nervous system (CNS) damage associated with psychostimulant dependence may be an ongoing, degenerative process with adverse effects on neuropsychiatric function. However, the molecular mechanisms regarding how altered energy regulation affects immune response in the context of substance use disorders are not fully understood. This review summarizes the current evidence regarding the effects of psychostimulant [particularly 3,4-methylenedioxy-N-methylamphetamine (MDMA) and methamphetamine] exposure on brain energy regulation, immune response, and neuropsychiatric function. Importantly, the neuropsychiatric impairments (e.g., cognitive deficits, depression, and anxiety) that persist following abstinence are associated with poorer treatment outcomes - increased relapse rates, lower treatment retention rates, and reduced daily functioning. Qualifying the molecular changes within the CNS according to the exposure and use patterns of specifically abused substances should inform the development of new therapeutic approaches for addiction treatment. Published by Elsevier B.V.
C1 [Downey, Luke A.] Swinburne Univ Technol, Ctr Human Psychopharmacol, Hawthorn, Vic 3122, Australia.
[Downey, Luke A.] Swansea Univ, Dept Psychol, Swansea, W Glam, Wales.
[Loftis, Jennifer M.] Portland VA Med Ctr, Res & Dev Serv, Portland, OR 97239 USA.
[Loftis, Jennifer M.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA.
[Loftis, Jennifer M.] Oregon Hlth & Sci Univ, Methamphetamine Abuse Res Ctr, Portland VA Med Ctr, Portland, OR 97239 USA.
RP Loftis, JM (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97239 USA.
EM loftisj@ohsu.edu
FU National Institute on Drug Abuse (NIDA), National Institutes of Health
(NIH) [DA028537, DA018165]; National Health and Medical Research Council
(NHMRC) [APP1054279]
FX The research discussed in this review was in part supported by National
Institute on Drug Abuse (NIDA), National Institutes of Health (NIH)
Grants (DA028537 and DA018165). This material was also supported with
resources and the use of facilities at the Portland Veterans Affairs
(VA) Medical Center and Oregon Health & Sciences University. Dr.
Jennifer Loftis is a Research Scientist at the Portland VA Medical
Center, Dr. Luke Downey is supported by a National Health and Medical
Research Council (NH&MRC) biomedical fellowship (APP1054279).
NR 66
TC 5
Z9 5
U1 3
U2 19
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-2999
EI 1879-0712
J9 EUR J PHARMACOL
JI Eur. J. Pharmacol.
PD MAR 15
PY 2014
VL 727
BP 125
EP 129
DI 10.1016/j.ejphar.2014.01.032
PG 5
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AC8EY
UT WOS:000332767500016
PM 24485894
ER
PT J
AU Winey, B
Shih, HA
Sahoo, N
Lee, A
Vapiwala, N
Both, S
AF Winey, Brian
Shih, Helen A.
Sahoo, Narayan
Lee, Andrew
Vapiwala, Neha
Both, Stefan
TI Core Physics Competencies for Proton Therapy Training of Radiation
Oncology and Medical Physics Residents and Fellows
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Editorial Material
C1 [Winey, Brian; Shih, Helen A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Winey, Brian; Shih, Helen A.] Harvard Univ, Sch Med, Boston, MA USA.
[Sahoo, Narayan; Lee, Andrew] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Vapiwala, Neha; Both, Stefan] Univ Penn, Philadelphia, PA 19104 USA.
RP Winey, B (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 35 Fruit St, Boston, MA 02114 USA.
EM winey.brian@mgh.harvard.edu
NR 10
TC 1
Z9 1
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
EI 1879-355X
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD MAR 15
PY 2014
VL 88
IS 4
BP 971
EP 972
DI 10.1016/j.ijrobp.2013.11.234
PG 2
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA AC4YN
UT WOS:000332527400032
PM 24606858
ER
PT J
AU Pohar, S
Fung, CY
Olsen, C
AF Pohar, Surjeet
Fung, Claire Y.
Olsen, Christine
TI American Society for Radiation Oncology (ASTRO) 2012 Workforce Study:
The Radiation Oncologists' and Residents' Perspectives Reply
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Editorial Material
C1 [Pohar, Surjeet] Indiana Univ Hlth Morgan Hosp, Dept Radiat Oncol, Martinsville, IN 46151 USA.
[Fung, Claire Y.] Commonwealth Newburyport Canc Ctr, Newburyport, MA USA.
[Olsen, Christine] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Pohar, S (reprint author), Indiana Univ Hlth Morgan Hosp, Dept Radiat Oncol, Martinsville, IN 46151 USA.
OI Pohar, Surjeet/0000-0002-8206-6462
NR 3
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
EI 1879-355X
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD MAR 15
PY 2014
VL 88
IS 4
BP 979
EP 979
DI 10.1016/j.ijrobp.2013.12.018
PG 1
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA AC4YN
UT WOS:000332527400036
PM 24606862
ER
PT J
AU Morandi, F
Di Carlo, E
Ferrone, S
Petretto, A
Pistoia, V
Airoldi, I
AF Morandi, Fabio
Di Carlo, Emma
Ferrone, Soldano
Petretto, Andrea
Pistoia, Vito
Airoldi, Irma
TI IL-27 in Human Secondary Lymphoid Organs Attracts Myeloid Dendritic
Cells and Impairs HLA Class I-Restricted Antigen Presentation
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CD4(+) T-CELLS; PROINFLAMMATORY CYTOKINE PRODUCTION;
MONOCLONAL-ANTIBODIES; ENDOPLASMIC-RETICULUM; IL-17 PRODUCTION;
FLOW-CYTOMETRY; B-CELLS; INTERLEUKIN-27; RECEPTOR; WSX-1
AB Different cytokines play crucial roles in inflammation and in polarizing immune responses, including IL-27 that exerts pro-and anti-inflammatory functions. Although the activity of IL-27 is well characterized in murine immune cells, only limited information is available regarding the natural cellular sources of IL-27 in humans and its effects on human immune cells. Dendritic cells (DCs) are the most potent professional APCs that in the immature state are positioned throughout peripheral tissues by acting as sentinels, sensing the presence of Ags. Activated DCs migrate into the lymph nodes and direct Ag-specific T cell responses, thus acting as key players in both adaptive and innate immunity. In this study we asked whether IL-27 is produced by human secondary lymphoid organs and what is its functional role on human DCs. To our knowledge, we provide the first evidence that 1) in lymph nodes, macrophages are the major source for IL-27; 2) immature and mature human DCs express functional IL-27R; 3) IL-27 exerts immunosuppressive activity by crippling the Ag processing machinery in immature DCs under steady-state conditions and after pulsing with a viral Ag; and 4) IL-27 is chemotactic for human DCs. Our findings highlight novel mechanisms underlying the immunosuppressive activity of IL-27, suggesting that this cytokine may function as a homeostatic cytokine in secondary lymphoid organs by limiting duration and/or intensity of ongoing adaptive immune responses. The results presented in this study pave the way to future studies aimed at investigating whether dysregulation of IL-27 expression and function may be involved in pathogenesis of autoimmune disease and cancer.
C1 [Morandi, Fabio; Pistoia, Vito; Airoldi, Irma] Ist Giannina Gaslini, Lab Oncol, I-16147 Genoa, Italy.
[Di Carlo, Emma] Univ G DAnnunzio, Dept Med & Sci Aging, I-66013 Chieti, Italy.
[Di Carlo, Emma] Univ G DAnnunzio Fdn, Ctr Aging Sci, I-66013 Chieti, Italy.
[Ferrone, Soldano] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Petretto, Andrea] Ist Giannina Gaslini, Lab Immunol Clin & Sperimentale, I-16147 Genoa, Italy.
RP Airoldi, I (reprint author), Ist Giannina Gaslini, Lab Oncol, Via Gerolamo Gaslini 1, I-16147 Genoa, Italy.
EM irmaairoldi@ospedale-gaslini.ge.it
OI Morandi, Fabio/0000-0002-2849-7595
FU Associazione Italiana Ricerca sul Cancro (Milan, Italy) [13018]; Ricerca
Finalizzata Collaboratore Estero Ministero della Salute
[RF-2010-2308270]; Cinque per Mille e Ricerca Corrente, Ministero della
Salute
FX This work was supported by Associazione Italiana Ricerca sul Cancro
(Milan, Italy) Grant 13018 (to I. A.), Ricerca Finalizzata Collaboratore
Estero Ministero della Salute Grant RF-2010-2308270 (to I. A.), and by
Cinque per Mille e Ricerca Corrente, Ministero della Salute.
NR 33
TC 4
Z9 5
U1 1
U2 4
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 MAR 15
PY 2014
VL 192
IS 6
BP 2634
EP 2642
DI 10.4049/jimmunol.1302656
PG 9
WC Immunology
SC Immunology
GA AC7IX
UT WOS:000332702700012
PM 24554774
ER
PT J
AU Kim-Howard, X
Sun, C
Molineros, JE
Maiti, AK
Chandru, H
Adler, A
Wiley, GB
Kaufman, KM
Kottyan, L
Guthridge, JM
Rasmussen, A
Kelly, J
Sanchez, E
Raj, P
Li, QZ
Bang, SY
Lee, HS
Kim, TH
Kang, YM
Suh, CH
Chung, WT
Park, YB
Choe, JY
Shim, SC
Lee, SS
Han, BG
Olsen, NJ
Karp, DR
Moser, K
Pons-Estel, BA
Wakeland, EK
James, JA
Harley, JB
Bae, SC
Gaffney, PM
Alarcon-Riquelme, M
Looger, LL
Nath, SK
AF Kim-Howard, Xana
Sun, Celi
Molineros, Julio E.
Maiti, Amit K.
Chandru, Hema
Adler, Adam
Wiley, Graham B.
Kaufman, Kenneth M.
Kottyan, Leah
Guthridge, Joel M.
Rasmussen, Astrid
Kelly, Jennifer
Sanchez, Elena
Raj, Prithvi
Li, Quan-Zhen
Bang, So-Young
Lee, Hye-Soon
Kim, Tae-Hwan
Kang, Young Mo
Suh, Chang-Hee
Chung, Won Tae
Park, Yong-Beom
Choe, Jung-Yoon
Shim, Seung Cheol
Lee, Shin-Seok
Han, Bok-Ghee
Olsen, Nancy J.
Karp, David R.
Moser, Kathy
Pons-Estel, Bernardo A.
Wakeland, Edward K.
James, Judith A.
Harley, John B.
Bae, Sang-Cheol
Gaffney, Patrick M.
Alarcon-Riquelme, Marta
Looger, Loren L.
Nath, Swapan K.
CA GENLES
TI Allelic heterogeneity in NCF2 associated with systemic lupus
erythematosus (SLE) susceptibility across four ethnic populations
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID CHRONIC GRANULOMATOUS-DISEASE; PHAGOCYTE NADPH OXIDASE; GENOME-WIDE
ASSOCIATION; RHEUMATOID-ARTHRITIS; GENETIC SUSCEPTIBILITY; RNA
SURVEILLANCE; REVISED CRITERIA; OXIDATIVE STRESS; CROHNS-DISEASE; RISK
LOCI
AB Recent reports have associated NCF2, encoding a core component of the multi-protein NADPH oxidase (NADPHO), with systemic lupus erythematosus (SLE) susceptibility in individuals of European ancestry. To identify ethnicity-specific and -robust variants within NCF2, we assessed 145 SNPs in and around the NCF2 gene in 5325 cases and 21 866 controls of European-American (EA), African-American (AA), Hispanic (HS) and Korean(KR) ancestry. Subsequent imputation, conditional, haplotype and bioinformatic analyses identified seven potentially functional SLE-predisposing variants. Association with non-synonymous rs17849502, previously reported in EA, was detected in EA, HS and AA (P-EA = 1.01 x 10(-54), P-HS = 3.68 x 10(-10), P-AA = 0.03); synonymous rs17849501 was similarly significant. These SNPs were monomorphic in KR. Novel associations were detected with coding variants at rs35937854 in AA (P-AA = 1.49 x 10(-9)), and rs13306575 in HS and KR (P-HS = 7.04 x 10(-7), P-KR = 3.30 x 10(-3)). In KR, a3-SNP haplotype was significantly associated (P 5 4.20 3 10 27), implying that SLE predisposing variants were tagged. Significant SNP-SNP interaction (P 5 0.02) was detected between rs13306575 and rs17849502 in HS, and adramatically increased risk(OR 5 6.55) with a risk allele at each locus. Molecular modeling predicts that these non-synonymous mutations could disrupt NADPHO complex assembly. The risk allele of rs17849501, located in a conserved transcriptional regulatory region, increased reporter gene activity, suggesting in vivo enhancer function. Our results not only establish allelic heterogeneity within NCF2 associated with SLE, but also emphasize the utility of multi-ethnic cohorts to identify predisposing variants explaining additional phenotypic variance ('missing heritability') of complex diseases like SLE.
C1 [Kim-Howard, Xana; Sun, Celi; Molineros, Julio E.; Maiti, Amit K.; Chandru, Hema; Adler, Adam; Wiley, Graham B.; Guthridge, Joel M.; Rasmussen, Astrid; Kelly, Jennifer; Sanchez, Elena; Moser, Kathy; James, Judith A.; Gaffney, Patrick M.; Alarcon-Riquelme, Marta; Nath, Swapan K.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA.
[Kaufman, Kenneth M.; Kottyan, Leah; Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Kaufman, Kenneth M.; Kottyan, Leah; Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA.
[Raj, Prithvi; Li, Quan-Zhen; Wakeland, Edward K.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
[Bang, So-Young; Lee, Hye-Soon; Kim, Tae-Hwan; Bae, Sang-Cheol] Hanyang Univ, Dept Rheumatol, Hosp Rheumat Dis, Seoul 133791, South Korea.
[Kang, Young Mo] Kyungpook Natl Univ Hosp, Taegu, South Korea.
[Suh, Chang-Hee] Ajou Univ Hosp, Suwon, South Korea.
[Chung, Won Tae] Dong A Univ Hosp, Pusan, South Korea.
[Park, Yong-Beom] Yonsei Univ, Coll Med, Dept Internal Med, Seoul, South Korea.
[Choe, Jung-Yoon] Daegu Catholic Univ Hosp, Taegu, South Korea.
[Shim, Seung Cheol] Chungnam Natl Univ Hosp, Daejeon Rheumatoid & Degenerat Arthrit Ctr, Taejon, South Korea.
[Lee, Shin-Seok] Chonnam Natl Univ Hosp, Kwangju, South Korea.
[Han, Bok-Ghee] Korea Natl Inst Hlth, Osong, South Korea.
[Olsen, Nancy J.] Penn State Med Sch, Dept Med, Div Rheumatol, Hershey, PA USA.
[Karp, David R.] Univ Texas Southwest Med Ctr, Dept Med, Div Rheumat Dis, Dallas, TX USA.
[Pons-Estel, Bernardo A.] Sanat Parque, Rosario, Santa Fe, Argentina.
[Looger, Loren L.] Howard Hughes Med Inst, Ashburn, VA USA.
RP Nath, SK (reprint author), Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 1025 NE 13th St, Oklahoma City, OK 73104 USA.
EM swapan-nath@omrf.org
RI Sanchez, Elena/B-4140-2017;
OI Sanchez, Elena/0000-0002-7041-5485; Kottyan, Leah/0000-0003-3979-2220;
Suh, Chang-Hee/0000-0001-6156-393X
FU US National Institutes of Health [AI103399, AR060366, AI094377,
AI083194, CA141700, AR058621, AI101934, AI082714, AR053483, GM103510,
GM103456, A121983]; Ministry for Health & Welfare, Republic of Korea
FX This work was supported by grants from the US National Institutes of
Health (AI103399, AR060366, AI094377, AI083194, CA141700, AR058621,
AI101934, AI082714, AR053483, GM103510, GM103456) and A121983, the Korea
Healthcare Technology R&D Project, Ministry for Health & Welfare,
Republic of Korea.
NR 98
TC 15
Z9 15
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD MAR 15
PY 2014
VL 23
IS 6
BP 1656
EP 1668
DI 10.1093/hmg/ddt532
PG 13
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA AB8MK
UT WOS:000332044300022
PM 24163247
ER
PT J
AU Perez, VB
Woods, SW
Roach, BJ
Ford, JM
McGlashan, TH
Srihari, VH
Mathalon, DH
AF Perez, Veronica B.
Woods, Scott W.
Roach, Brian J.
Ford, Judith M.
McGlashan, Thomas H.
Srihari, Vinod H.
Mathalon, Daniel H.
TI Automatic Auditory Processing Deficits in Schizophrenia and Clinical
High-Risk Patients: Forecasting Psychosis Risk with Mismatch Negativity
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Auditory cortex; clinical high-risk for psychosis; event-related
potential; longitudinal; mismatch negativity; psychosis; schizophrenia
ID EVENT-RELATED POTENTIALS; D-ASPARTATE RECEPTORS; ULTRA-HIGH-RISK;
1ST-EPISODE SCHIZOPHRENIA; INTERRATER RELIABILITY; SELECTIVE-ATTENTION;
PREDICTIVE-VALIDITY; PRODROMAL SYNDROMES; SPECTRUM DISORDERS; STIMULUS
DEVIANCE
AB Background: Only about one third of patients at high risk for psychosis based on current clinical criteria convert to a psychotic disorder within a 2.5-year follow-up period. Targeting clinical high-risk (CHR) individuals for preventive interventions could expose many to unnecessary treatments, underscoring the need to enhance predictive accuracy with nonclinical measures. Candidate measures include event-related potential components with established sensitivity to schizophrenia. Here, we examined the mismatch negativity (MMN) component of the event-related potential elicited automatically by auditory deviance in CHR and early illness schizophrenia (ESZ) patients. We also examined whether MMN predicted subsequent conversion to psychosis in CHR patients.
Methods: Mismatch negativity to auditory deviants (duration, frequency, and duration + frequency double deviant) was assessed in 44 healthy control subjects, 19 ESZ, and 38 CHR patients. Within CHR patients, 15 converters to psychosis were compared with 16 nonconverters with at least 12 months of clinical follow-up. Hierarchical Cox regression examined the ability of MMN to predict time to psychosis onset in CHR patients.
Results: Irrespective of deviant type, MMN was significantly reduced in ESZ and CHR patients relative to healthy control subjects and in CHR converters relative to nonconverters. Mismatch negativity did not significantly differentiate ESZ and CHR patients. The duration + frequency double deviant MMN, but not the single deviant MMNs, significantly predicted the time to psychosis onset in CHR patients.
Conclusions: Neurophysiological mechanisms underlying automatic processing of auditory deviance, as reflected by the duration + frequency double deviant MMN, are compromised before psychosis onset and can enhance the prediction of psychosis risk among CHR patients.
C1 [Perez, Veronica B.; Roach, Brian J.; Ford, Judith M.; Mathalon, Daniel H.] Univ Calif San Francisco, San Francisco, CA 94121 USA.
[Perez, Veronica B.; Roach, Brian J.; Ford, Judith M.; Mathalon, Daniel H.] San Francisco Vet Adm Med Ctr, San Francisco, CA USA.
[Woods, Scott W.; McGlashan, Thomas H.; Srihari, Vinod H.] Yale Univ, Sch Med, New Haven, CT USA.
RP Mathalon, DH (reprint author), Univ Calif San Francisco, San Francisco Vet Adm Med Ctr, Mental Hlth Serv 116D, 4150 Clement St, San Francisco, CA 94121 USA.
EM daniel.mathalon@ucsf.edu
OI Mathalon, Daniel/0000-0001-6090-4974; Roach, Brian/0000-0002-3264-1465;
Srihari, Vinod/0000-0003-1556-2332
FU National Institutes of Health [R01 MH076989, U01 MH082022, K02 MH067967,
T32 MH089920]; Brain and Behavior Research Foundation
FX This study was supported by grants from the National Institutes of
Health (R01 MH076989, U01 MH082022, K02 MH067967, and T32 MH089920) and
from the Brain and Behavior Research Foundation.
NR 89
TC 33
Z9 35
U1 4
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
EI 1873-2402
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAR 15
PY 2014
VL 75
IS 6
BP 459
EP 469
DI 10.1016/j.biopsych.2013.07.038
PG 11
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AB4AK
UT WOS:000331731100006
PM 24050720
ER
PT J
AU Lee, TH
Chang, J
Kim, BM
AF Lee, Tae Ho
Chang, Jihoon
Kim, Byeong Mo
TI Saikosaponin C inhibits lipopolysaccharide-induced apoptosis by
suppressing caspase-3 activation and subsequent degradation of focal
adhesion kinase in human umbilical vein endothelial cells
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Lipopolysaccharide (LPS); Human umbilical vein endothelial cells
(HUVECs); Endothelial cell apoptosis; Saikosaponin C (SSc); Caspase-3;
Focal adhesion kinase (FAK)
ID SOLUBLE CD14; CLEAVAGE; SURVIVAL; MECHANISM; PROTEINS; PATHWAY; GROWTH;
INJURY; LINE
AB Bacterial lipopolysaccharide (LPS) is an important mediator of inflammation and a potent inducer of endothelial cell damage and apoptosis. In this study, we investigated the protective effects of saikosaponin C (SSc), one of the active ingredients produced by the traditional Chinese herb, Radix Bupleuri, against LPS-induced apoptosis in human umbilical endothelial cells (HUVECs). LPS triggered caspase-3 activation, which was found to be important in LPS-induced HUVEC apoptosis. Inhibition of caspase-3 also inhibited LPS-induced degradation of focal adhesion kinase (FAK), indicating that caspase-3 is important in LPS-mediated FAK degradation as well as in apoptosis in HUVECs. SSc significantly inhibited LPS-induced apoptotic cell death in HUVECs through the selective suppression of caspase-3. SSc was also shown to rescue LPS-induced FAK degradation and other cell adhesion signals. Furthermore, the protective effects of SSc against LPS-induced apoptosis were abolished upon pretreatment with a FAK inhibitor, highlighting the importance of FAK in SSc activity. Taken together, these results show that SSc efficiently inhibited LPS-induced apoptotic cell death via inhibition of caspase-3 activation and caspase-3-mediated-FAK degradation. Therefore, SSc represents a promising therapeutic candidate for the treatment of vascular endothelial cell injury and cellular dysfunction. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Lee, Tae Ho; Kim, Byeong Mo] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gerontol,Dept Med, Boston, MA 02215 USA.
[Chang, Jihoon] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA.
RP Kim, BM (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gerontol,Dept Med, Boston, MA 02215 USA.
EM bkim2@bidmc.harvard.edu
FU Korean Government [NRF-2011-356-C00085]; National Research Foundation of
Korea Grant
FX This work was supported by the National Research Foundation of Korea
Grant funded by the Korean Government (NRF-2011-356-C00085).
NR 26
TC 6
Z9 6
U1 1
U2 17
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
EI 1090-2104
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD MAR 14
PY 2014
VL 445
IS 3
BP 615
EP 621
DI 10.1016/j.bbrc.2014.02.046
PG 7
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA AE9JC
UT WOS:000334323100014
PM 24565837
ER
PT J
AU Wang, J
Bi, WN
Cheng, A
Freire, D
Vempati, P
Zhao, W
Gong, B
Janle, EM
Chen, TY
Ferruzzi, MG
Schmeidler, J
Ho, L
Pasinetti, GM
AF Wang, Jun
Bi, Weina
Cheng, Alice
Freire, Daniel
Vempati, Prashant
Zhao, Wei
Gong, Bing
Janle, Elsa M.
Chen, Tzu-Ying
Ferruzzi, Mario G.
Schmeidler, James
Ho, Lap
Pasinetti, Giulio M.
TI Targeting multiple pathogenic mechanisms with polyphenols for the
treatment of Alzheimer's disease-experimental approach and therapeutic
implications
SO FRONTIERS IN AGING NEUROSCIENCE
LA English
DT Article
DE Alzheimer's disease (AD); polyphenols; grape seed extract; grape juice;
resveratrol; J20 mice
ID LONG-TERM POTENTIATION; MOUSE MODEL; COGNITIVE DETERIORATION; TRANSGENIC
MICE; RESVERATROL; NEUROPATHOLOGY; BRAIN; INFLAMMATION; SUPPLEMENTATION;
CONSUMPTION
AB Alzheimer's disease (AD) is the most prevalent neurodegenerative disease of aging and currently has no cure. Its onset and progression are influenced by multiple factors. There is growing consensus that successful treatment will rely on simultaneously targeting multiple pathological features of AD. Polyphenol compounds have many proven health benefits. In this study, we tested the hypothesis that combining three polyphenolic preparations (grape seed extract, resveratrol, and Concord grape juice extract), with different polyphenolic compositions and partially redundant bioactivities, may simultaneously and synergistically mitigate amyloid-beta (A beta) mediated neuropathology and cognitive impairments in a mouse model of AD. We found that administration of the polyphenols in combination did not alter the profile of bioactive polyphenol metabolites in the brain. We also found that combination treatment resulted in better protection against cognitive impairments compared to individual treatments, in J20 AD mice. Electrophysiological examination showed that acute treatment with select brain penetrating polyphenol metabolites, derived from these polyphenols, improved oligomeric A beta (oA beta)-induced long term potentiation (LIP) deficits in hippocampal slices. Moreover, we found greatly reduced total amyloid content in the brain following combination treatment. Our studies provided experimental evidence that application of polyphenols targeting multiple disease-mechanisms may yield a greater likelihood of therapeutic efficacy.
C1 [Wang, Jun; Bi, Weina; Cheng, Alice; Freire, Daniel; Vempati, Prashant; Zhao, Wei; Gong, Bing; Ho, Lap; Pasinetti, Giulio M.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY USA.
[Wang, Jun; Pasinetti, Giulio M.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA.
[Janle, Elsa M.; Chen, Tzu-Ying; Ferruzzi, Mario G.] Purdue Univ, Dept Food Sci, W Lafayette, IN 47907 USA.
[Janle, Elsa M.; Chen, Tzu-Ying; Ferruzzi, Mario G.] Purdue Univ, Dept Foods & Nutr, W Lafayette, IN 47907 USA.
[Schmeidler, James] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY USA.
RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Dept Neurol, 1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA.
EM giulio.pasinetti@mssm.edu
NR 51
TC 22
Z9 24
U1 1
U2 29
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1663-4365
J9 FRONT AGING NEUROSCI
JI Front. Aging Neurosci.
PD MAR 14
PY 2014
VL 6
AR 42
DI 10.3389/fnagi.2014.00042
PG 10
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA AC9HX
UT WOS:000332846300001
PM 24672477
ER
PT J
AU Xiao, L
Zhang, CK
Li, XH
Gong, SC
Hu, RM
Balasubramanian, R
Crowley Jr, WF
Hastings, MH
Zhou, QY
AF Xiao, Ling
Zhang, Chengkang
Li, Xiaohan
Gong, Shiaoching
Hu, Renming
Balasubramanian, Ravikumar
Crowley, William F. W., Jr.
Hastings, Michael H.
Zhou, Qun-Yong
TI Signaling Role of Prokineticin 2 on the Estrous Cycle of Female Mice
SO PLOS ONE
LA English
DT Article
ID LUTEINIZING-HORMONE SURGE; IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM;
SUPRACHIASMATIC NUCLEUS; CIRCADIAN-RHYTHMS; EFFERENT PROJECTIONS;
OLFACTORY-BULB; PREOPTIC AREA; NEURONS; KISSPEPTIN; RATS
AB The possible signaling role of prokineticin 2 (PK2) and its receptor, prokineticin receptor 2 (PKR2), on female reproduction was investigated. First, the expression of PKR2 and its co-localization with estrogen receptor (ER alpha) in the hypothalamus was examined. Sexually dimorphic expression of PKR2 in the preoptic area of the hypothalamus was observed. Compared to the male mice, there was more widespread PKR2 expression in the preoptic area of the hypothalamus in the female mice. The likely co-expression of PKR2 and ERa in the preoptic area of the hypothalamus was observed. The estrous cycles in female PK2-null, and PKR2-null heterozygous mice, as well as in PK2-null and PKR2-null compound heterozygous mice were examined. Loss of one copy of PK2 or PKR2 gene caused elongated and irregular estrous cycle in the female mice. The alterations in the estrous cycle were more pronounced in PK2-null and PKR2-null compound heterozygous mice. Consistent with these observations, administration of a small molecule PK2 receptor antagonist led to temporary blocking of estrous cycle at the proestrous phase in female mice. The administration of PKR2 antagonist was found to blunt the circulating LH levels. Taken together, these studies indicate PK2 signaling is required for the maintenance of normal female estrous cycles.
C1 [Xiao, Ling; Zhang, Chengkang; Li, Xiaohan; Zhou, Qun-Yong] Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92717 USA.
[Xiao, Ling] Fudan Univ, Jinshan Hosp, Dept Endocrinol, Shanghai 200433, Peoples R China.
[Gong, Shiaoching] Rockefeller Univ, GENSAT Project, New York, NY 10021 USA.
[Hu, Renming] Fudan Univ, Huashan Hosp, Inst Endocrinol & Diabetol, Shanghai 200433, Peoples R China.
[Balasubramanian, Ravikumar; Crowley, William F. W., Jr.] Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr, Boston, MA 02114 USA.
[Balasubramanian, Ravikumar; Crowley, William F. W., Jr.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA.
[Hastings, Michael H.] Med Res Council Lab Mol Biol, Div Neurobiol, Cambridge, England.
RP Zhou, QY (reprint author), Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92717 USA.
EM qzhou@uci.edu
OI Hastings, Michael Harvey/0000-0001-8576-6651
FU NIH [HD15788]
FX This work was supported by NIH grant HD15788. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 45
TC 1
Z9 1
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 14
PY 2014
VL 9
IS 3
AR e90860
DI 10.1371/journal.pone.0090860
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC9MJ
UT WOS:000332858400022
PM 24633064
ER
PT J
AU Mulak, A
Tache, Y
Larauche, M
AF Mulak, Agata
Tache, Yvette
Larauche, Muriel
TI Sex hormones in the modulation of irritable bowel syndrome
SO WORLD JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
DE Brain-gut axis; Irritable bowel syndrome; Microbiota; Pain modulation;
Sex hormones
ID INDUCED VISCERAL HYPERSENSITIVITY; CORTICOTROPIN-RELEASING HORMONE;
MESSENGER-RNA EXPRESSION; ESTROGEN-RECEPTOR-ALPHA; FUNCTIONAL
GASTROINTESTINAL DISORDERS; MAST-CELL SECRETION; MENSTRUAL-CYCLE; FEMALE
RATS; GUT MICROBIOTA; POSTMENOPAUSAL WOMEN
AB Compelling evidence indicates sex and gender differences in epidemiology, symptomatology, pathophysiology, and treatment outcome in irritable bowel syndrome (IBS). Based on the female predominance as well as the correlation between IBS symptoms and hormonal status, several models have been proposed to examine the role of sex hormones in gastrointestinal (GI) function including differences in GI symptoms expression in distinct phases of the menstrual cycle, in pre- and post-menopausal women, during pregnancy, hormonal treatment or after oophorectomy. Sex hormones may influence peripheral and central regulatory mechanisms of the brain-gut axis involved in the pathophysiology of IBS contributing to the alterations in visceral sensitivity, motility, intestinal barrier function, and immune activation of intestinal mucosa. Sex differences in stress response of the hypothalamic-pituitary-adrenal axis and autonomic nervous system, neuroimmune interactions triggered by stress, as well as estrogen interactions with serotonin and corticotropin-releasing factor signaling systems are being increasingly recognized. A concept of "microgenderome" related to the potential role of sex hormone modulation of the gut microbiota is also emerging. Significant differences between IBS female and male patients regarding symptomatology and comorbidity with other chronic pain syndromes and psychiatric disorders, together with differences in efficacy of serotonergic medications in IBS patients confirm the necessity for more sex-tailored therapeutic approach in this disorder. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.
C1 [Mulak, Agata] Wroclaw Med Univ, Dept Gastroenterol & Hepatol, PL-50556 Wroclaw, Poland.
[Tache, Yvette; Larauche, Muriel] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA.
[Tache, Yvette; Larauche, Muriel] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Oppenheimer Family Ctr Neurobiol Stress, Dept Med,Div Digest Dis, Los Angeles, CA 90073 USA.
RP Mulak, A (reprint author), Wroclaw Med Univ, Dept Gastroenterol & Hepatol, Borowska 213, PL-50556 Wroclaw, Poland.
EM agata.mulak@wp.pl
OI Larauche, Muriel/0000-0003-3320-3675
FU The Veterans Administration Research Career Scientist Award; National
Institute of Health [P50 DK-64539, K01-DK088937]
FX Supported by The Veterans Administration Research Career Scientist Award
(to Tache Y); National Institute of Health grants No. P50 DK-64539 (to
Tache Y); and No. K01-DK088937 (to Larauche M)
NR 164
TC 31
Z9 31
U1 4
U2 40
PU BAISHIDENG PUBLISHING GROUP INC
PI PLEASANTON
PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA
SN 1007-9327
EI 2219-2840
J9 WORLD J GASTROENTERO
JI World J. Gastroenterol.
PD MAR 14
PY 2014
VL 20
IS 10
BP 2433
EP 2448
DI 10.3748/wjg.v20.i10.2433
PG 16
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AC7GY
UT WOS:000332697400002
PM 24627581
ER
PT J
AU Hunter, ZR
Xu, L
Yang, G
Zhou, YS
Liu, X
Cao, Y
Manning, RJ
Tripsas, C
Patterson, CJ
Sheehy, P
Treon, SP
AF Hunter, Zachary R.
Xu, Lian
Yang, Guang
Zhou, Yangsheng
Liu, Xia
Cao, Yang
Manning, Robert J.
Tripsas, Christina
Patterson, Christopher J.
Sheehy, Patricia
Treon, Steven P.
TI The genomic landscape of Waldenstrom macroglobulinemia is characterized
by highly recurring MYD88 and WHIM-like CXCR4 mutations, and small
somatic deletions associated with B-cell lymphomagenesis
SO BLOOD
LA English
DT Article
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; NF-KAPPA-B; CHRONIC LYMPHOCYTIC-LEUKEMIA;
IGM MONOCLONAL GAMMOPATHY; BRUTONS TYROSINE KINASE; UNDETERMINED
SIGNIFICANCE; TUMOR-SUPPRESSOR; RECEPTOR INTERNALIZATION; BINDING
PROTEIN; TARGET GENES
AB The genetic basis for Waldenstrom macroglobulinemia (WM) remains to be clarified. Although 6q losses are commonly present, recurring gene losses in this region remain to be defined. We therefore performed whole genome sequencing (WGS) in 30 WM patients, which included germline/tumor sequencing for 10 patients. Validated somatic mutations occurring in >10% of patients includedMYD88, CXCR4, and ARID1A that were present in 90%, 27%, and 17% of patients, respectively, and included the activating mutation L265P in MYD88 and warts, hypogammaglobulinemia, infection, and myelokathexis-syndrome-like mutations in CXCR4 that previously have only been described in the germline. WGS also delineated copy number alterations (CNAs) and structural variants in the 10 paired patients. The CXCR4 and CNA findings were validated in independent expansion cohorts of 147 and 30WM patients, respectively. Validated gene losses due to CNAs involved PRDM2 (93%), BTG1 (87%), HIVEP2 (77%), MKLN1 (77%), PLEKHG1 (70%), LYN (60%), ARID1B (50%), and FOXP1 (37%). Losses in PLEKHG1, HIVEP2, ARID1B, and BCLAF1 constituted the most common deletions within chromosome 6. Although no recurrent translocations were observed, in 2 patients deletions in 6q corresponded with translocation events. These studies evidence highly recurring somatic events, and provide a genomic basis for understanding the pathogenesis of WM.
C1 [Hunter, Zachary R.; Xu, Lian; Yang, Guang; Zhou, Yangsheng; Liu, Xia; Cao, Yang; Manning, Robert J.; Tripsas, Christina; Patterson, Christopher J.; Sheehy, Patricia; Treon, Steven P.] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02215 USA.
[Hunter, Zachary R.] Boston Univ, Grad Sch Med Sci, Dept Pathol & Lab Med, Boston, MA 02215 USA.
[Treon, Steven P.] Harvard Univ, Sch Med, Boston, MA USA.
RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, M547,450 Brookline Ave, Boston, MA 02215 USA.
EM steven_treon@dfci.harvard.edu
RI Hunter, Zachary/H-3018-2013
OI Hunter, Zachary/0000-0002-1689-1691
FU International Waldenstrom's Macroglobulinemia Foundation; Coyote Fund
for Waldenstrom's Macroglobulinemia; D'Amato Family Fund for Genomic
Discovery; Edward and Linda Nelson Fund for Waldenstrom's
Macroglobulinemia Research
FX This work was supported by Peter S. Bing, the International
Waldenstrom's Macroglobulinemia Foundation, the Coyote Fund for
Waldenstrom's Macroglobulinemia, the D'Amato Family Fund for Genomic
Discovery, the Edward and Linda Nelson Fund for Waldenstrom's
Macroglobulinemia Research, and the WM patients who provided their
samples.
NR 70
TC 66
Z9 66
U1 1
U2 10
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAR 13
PY 2014
VL 123
IS 11
BP 1637
EP 1646
DI 10.1182/blood-2013-09-525808
PG 10
WC Hematology
SC Hematology
GA AH0YW
UT WOS:000335847700010
PM 24366360
ER
PT J
AU Chang, JE
Li, HL
Smith, MR
Gascoyne, RD
Paietta, EM
Yang, DT
Advani, RH
Horning, SJ
Kahl, BS
AF Chang, Julie E.
Li, Hailun
Smith, Mitchell R.
Gascoyne, Randy D.
Paietta, Elisabeth M.
Yang, David T.
Advani, Ranjana H.
Horning, Sandra J.
Kahl, Brad S.
TI Phase 2 study of VcR-CVAD with maintenance rituximab for untreated
mantle cell lymphoma: an Eastern Cooperative Oncology Group study
(E1405)
SO BLOOD
LA English
DT Article
ID PROGRESSION-FREE SURVIVAL; STUDY-GROUP GLSG; INDUCTION
CHEMOIMMUNOTHERAPY; PLUS CHEMOTHERAPY; BORTEZOMIB; TRIAL;
CYCLOPHOSPHAMIDE; MULTICENTER; COMBINATION; DOXORUBICIN
AB Rituximab, bortezomib, modified hyper-cyclophosphamide, doxorubicin, vincristine, dexamethasone (VcR-CVAD) induction chemoimmunotherapy and maintenance rituximab (MR) were evaluated for efficacy and safety in Eastern Cooperative Oncology Group protocol E1405. Patients with previously untreated mantle cell lymphoma received VcR-CVAD chemotherapy every 21 days for 6 cycles, followed by MR for 2 years. Transplant-eligible patients had the option of autologous stem cell transplantation (ASCT) consolidation instead of MR. The primary end point was the complete response (CR) rate to VcR-CVAD. The secondary end points were overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and toxicities. Seventy-five eligible patients with a median age of 62 (range 40-76) were enrolled. The ORR was 95% and a CR was achieved in 68% of patients. After a median follow-up of 4.5 years, 3-year PFS and OS were 72% and 88%, respectively. No substantial difference in PFS or OS was observed between patients treated with MR (n = 44) vs ASCT (n = 22). There were no unexpected toxicities. VcR-CVAD produced high ORR and CR rates in mantle cell lymphoma. MR after VcR-CVAD induction performed similarly to ASCT and may improve response duration. Randomized clinical trials comparing MR against ASCT should be considered and randomized clinical trials evaluating bortezomib's contribution to conventional therapy are under way. This study was registered at www.clinicaltrials.gov as #NCT00433537.
C1 [Chang, Julie E.; Yang, David T.; Kahl, Brad S.] Univ Wisconsin, Madison, WI 53705 USA.
[Li, Hailun] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Smith, Mitchell R.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA.
[Gascoyne, Randy D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
[Paietta, Elisabeth M.] Montefiore Med Ctr, North Div, Bronx, NY 10467 USA.
[Advani, Ranjana H.] Stanford Univ, Stanford, CA 94305 USA.
[Horning, Sandra J.] Genentech Inc, San Francisco, CA 94080 USA.
RP Kahl, BS (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Inst Med Res, 1111 Highland Ave,4059, Madison, WI 53705 USA.
EM bsk@medicine.wisc.edu
OI Smith, Mitchell/0000-0003-1428-8765
FU Public Health Service Grants [CA21115, CA23318, CA66636, CA27525,
CA21076, CA14958]; National Cancer Institute, National Institutes of
Health; Department of Health and Human Services
FX This study was conducted by the Eastern Cooperative Oncology Group
(Robert L. Comis, chair) and supported in part by Public Health Service
Grants (CA21115, CA23318, CA66636, CA27525, CA21076, and CA14958) and
from the National Cancer Institute, National Institutes of Health, and
the Department of Health and Human Services. Its contents are solely the
responsibility of the authors and do not necessarily represent the
official views of the National Cancer Institute.
NR 41
TC 25
Z9 28
U1 1
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAR 13
PY 2014
VL 123
IS 11
BP 1665
EP 1673
DI 10.1182/blood-2013-08-523845
PG 9
WC Hematology
SC Hematology
GA AH0YW
UT WOS:000335847700013
PM 24458437
ER
PT J
AU Chambwe, N
Kormaksson, M
Geng, HM
De, S
Michor, F
Johnson, NA
Morin, RD
Scott, DW
Godley, LA
Gascoyne, RD
Melnick, A
Campagne, F
Shaknovich, R
AF Chambwe, Nyasha
Kormaksson, Matthias
Geng, Huimin
De, Subhajyoti
Michor, Franziska
Johnson, Nathalie A.
Morin, Ryan D.
Scott, David W.
Godley, Lucy A.
Gascoyne, Randy D.
Melnick, Ari
Campagne, Fabien
Shaknovich, Rita
TI Variability in DNA methylation defines novel epigenetic subgroups of
DLBCL associated with different clinical outcomes
SO BLOOD
LA English
DT Article
ID B-CELL LYMPHOMA; ACUTE MYELOID-LEUKEMIA; CYTOSINE METHYLATION; SOMATIC
MUTATIONS; PROGNOSTIC-FACTOR; HODGKIN-LYMPHOMA; EXPRESSION;
METHYLTRANSFERASE; HYPERMETHYLATION; PROTEIN
AB Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive form of non-Hodgkin lymphoma with variable biology and clinical behavior. The current classification does not fully explain the biological and clinical heterogeneity of DLBCLs. In this study, we carried out genomewide DNA methylation profiling of 140 DLBCL samples and 10 normal germinal center B cells using the HpaII tiny fragment enrichment by ligation-mediated polymerase chain reaction assay and hybridization to a custom Roche NimbleGen promoter array. We defined methylation disruption as a main epigenetic event in DLBCLs and designed a method for measuring the methylation variability of individual cases. We then used a novel approach for unsupervised hierarchical clustering based on the extent of DNA methylation variability. This approach identified 6 clusters (A-F). The extent of methylation variability was associated with survival outcomes, with significant differences in overall and progression-free survival. The novel clusters are characterized by disruption of specific biological pathways such as cytokine-mediated signaling, ephrin signaling, and pathways associated with apoptosis and cell-cycle regulation. In a subset of patients, we profiled gene expression and genomic variation to investigate their interplay with methylation changes. This study is the first to identify novel epigenetic clusters of DLBCLs and their aberrantly methylated genes, molecular associations, and survival.
C1 [Chambwe, Nyasha; Campagne, Fabien] Weill Cornell Med Ctr, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, New York, NY USA.
[Chambwe, Nyasha; Campagne, Fabien] Weill Cornell Med Ctr, Dept Physiol & Biophys, New York, NY USA.
[Chambwe, Nyasha] Weill Cornell Med Ctr, Tri Inst Training Program Computat Biol & Med, New York, NY USA.
[Kormaksson, Matthias] Weill Cornell Med Ctr, Dept Publ Hlth, New York, NY USA.
[Kormaksson, Matthias] IBM Res Brazil, Rio De Janeiro, Brazil.
[Geng, Huimin] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
[De, Subhajyoti] Univ Colorado, Sch Med, Dept Med, Aurora, CO USA.
[De, Subhajyoti] Colorado Sch Publ Hlth, Dept Biostat & Informat, Aurora, CO USA.
[De, Subhajyoti] Univ Colorado, Ctr Canc, Mol Oncol Program, Aurora, CO USA.
[Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Johnson, Nathalie A.] McGill Univ, Jewish Gen Hosp, Dept Med, Montreal, PQ H3T 1E2, Canada.
[Morin, Ryan D.] Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada.
[Morin, Ryan D.] British Columbia Canc Agcy, Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada.
[Scott, David W.; Gascoyne, Randy D.] British Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 4E6, Canada.
[Godley, Lucy A.] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Gascoyne, Randy D.] Univ British Columbia, Dept Pathol, Vancouver, BC, Canada.
[Melnick, Ari] Weill Cornell Med Coll, Dept Pharmacol, New York, NY USA.
[Melnick, Ari; Shaknovich, Rita] Weill Cornell Med Coll, Div Hematol & Oncol, New York, NY USA.
[Shaknovich, Rita] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA.
RP Shaknovich, R (reprint author), Weill Cornell Med Coll, 1300 York Ave,Bldg C,Room 620C, New York, NY 10065 USA.
EM fac2003@campagnelab.org; ris9004@med.cornell.edu
OI Campagne, Fabien/0000-0001-6237-3564; Chambwe,
Nyasha/0000-0002-2812-0122
FU Tri-Institutional Training Program in Computational Biology and
Medicine; National Institutes of Health [K08 CA127353]; Leukemia &
Lymphoma Society [6304-11, U54CA143798]
FX This work was supported by grants from the Tri-Institutional Training
Program in Computational Biology and Medicine (N.C.), the National
Institutes of Health Clinical Investigator Award (K08 CA127353), and The
Leukemia & Lymphoma Society (6304-11) (R.S.) (U54CA143798) (S.D. and
F.M.).
NR 53
TC 24
Z9 24
U1 1
U2 4
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAR 13
PY 2014
VL 123
IS 11
BP 1699
EP 1708
DI 10.1182/blood-2013-07-509885
PG 10
WC Hematology
SC Hematology
GA AH0YW
UT WOS:000335847700017
PM 24385541
ER
PT J
AU Menche, J
Sharma, A
Cho, MH
Mayer, RJ
Rennard, SI
Celli, B
Miller, BE
Locantore, N
Tal-Singer, R
Ghosh, S
Larminie, C
Bradley, G
Riley, JH
Agusti, A
Silverman, EK
Barabasi, AL
AF Menche, Joerg
Sharma, Amitabh
Cho, Michael H.
Mayer, Ruth J.
Rennard, Stephen I.
Celli, Bartolome
Miller, Bruce E.
Locantore, Nick
Tal-Singer, Ruth
Ghosh, Soumitra
Larminie, Chris
Bradley, Glyn
Riley, John H.
Agusti, Alvar
Silverman, Edwin K.
Barabasi, Albert-Laszlo
TI A diVIsive Shuffling Approach (VIStA) for gene expression analysis to
identify subtypes in Chronic Obstructive Pulmonary Disease
SO BMC SYSTEMS BIOLOGY
LA English
DT Article; Proceedings Paper
CT High-Throughput Omics and Data Integration Workshop
CY FEB 13-15, 2013
CL Barcelona, SPAIN
ID SMOKERS; ECLIPSE; CANCER; TISSUE
AB Background: An important step toward understanding the biological mechanisms underlying a complex disease is a refined understanding of its clinical heterogeneity. Relating clinical and molecular differences may allow us to define more specific subtypes of patients that respond differently to therapeutic interventions.
Results: We developed a novel unbiased method called diVIsive Shuffling Approach (VIStA) that identifies subgroups of patients by maximizing the difference in their gene expression patterns. We tested our algorithm on 140 subjects with Chronic Obstructive Pulmonary Disease (COPD) and found four distinct, biologically and clinically meaningful combinations of clinical characteristics that are associated with large gene expression differences. The dominant characteristic in these combinations was the severity of airflow limitation. Other frequently identified measures included emphysema, fibrinogen levels, phlegm, BMI and age. A pathway analysis of the differentially expressed genes in the identified subtypes suggests that VIStA is capable of capturing specific molecular signatures within in each group.
Conclusions: The introduced methodology allowed us to identify combinations of clinical characteristics that correspond to clear gene expression differences. The resulting subtypes for COPD contribute to a better understanding of its heterogeneity.
C1 [Menche, Joerg; Sharma, Amitabh; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Networks Res, Boston, MA 02115 USA.
[Menche, Joerg; Sharma, Amitabh; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Boston, MA 02115 USA.
[Menche, Joerg; Sharma, Amitabh; Barabasi, Albert-Laszlo] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02215 USA.
[Menche, Joerg; Barabasi, Albert-Laszlo] Budapest Univ Technol & Econ, Dept Theoret Phys, H-1111 Budapest, Hungary.
[Cho, Michael H.; Silverman, Edwin K.] Harvard Univ, Sch Med, Channing Div Network Med, Boston, MA 02115 USA.
[Cho, Michael H.; Silverman, Edwin K.] Harvard Univ, Sch Med, Div Pulm & Crit Care Med, Dept Med,Brigham & Womens Hosp, Boston, MA 02115 USA.
[Mayer, Ruth J.; Miller, Bruce E.; Tal-Singer, Ruth; Ghosh, Soumitra] GlaxoSmithKline, King Of Prussia, PA 19406 USA.
[Rennard, Stephen I.] Univ Nebraska Med Ctr, Omaha, NE 68198 USA.
[Celli, Bartolome] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Pulm & Crit Care, Boston, MA 02115 USA.
[Locantore, Nick] GlaxoSmithKline, Res Triangle Pk, NC 27709 USA.
[Larminie, Chris; Bradley, Glyn; Riley, John H.] GlaxoSmithKline, Stevenage SG1 2NY, Herts, England.
[Agusti, Alvar] Univ Barcelona, Thorax Inst, IDIBAPS, Hosp Clin, E-08036 Barcelona, Spain.
[Barabasi, Albert-Laszlo] Cent European Univ, Ctr Network Sci, H-1051 Budapest, Hungary.
[Barabasi, Albert-Laszlo] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Agusti, Alvar] CIBERES, FISIB, Mallorca 07110, Spain.
RP Barabasi, AL (reprint author), Northeastern Univ, Ctr Complex Networks Res, Boston, MA 02115 USA.
EM barabasi@gmail.com
RI Menche, Jorg/G-3994-2015
OI Menche, Jorg/0000-0002-1583-6404
NR 18
TC 9
Z9 9
U1 0
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1752-0509
J9 BMC SYST BIOL
JI BMC Syst. Biol.
PD MAR 13
PY 2014
VL 8
SU 2
AR S8
DI 10.1186/1752-0509-8-S2-S8
PG 13
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA AE0UI
UT WOS:000333681300009
PM 25032995
ER
PT J
AU Cho, TA
Chi, AS
Schaefer, PW
Louis, DN
AF Cho, Tracey A.
Chi, Andrew S.
Schaefer, Pamela W.
Louis, David N.
TI Case 8-2014: A 29-Year- Old Man with Headache, Vomiting, and Diplopia
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID DIFFUSE LEPTOMENINGEAL GLIOMATOSIS; GLIOBLASTOMA-MULTIFORME; TUBERCULOUS
MENINGITIS; TEMOZOLOMIDE
AB A 29-year-old man was admitted to the hospital because of headache, vomiting, photophobia, diplopia, and stiff neck. He was born in Southeast Asia. Brain imaging showed diffuse leptomeningeal enhancement. Cultures were sterile. A diagnostic procedure was performed. Presentation of CaseDr. Xuemei Cai (Neurology): A 29-year-old man was admitted to this hospital because of headache, vomiting, and diplopia. The patient had been well until 3 weeks before admission, when headaches, blurred vision, nausea, and vomiting developed, followed by anorexia and weight loss (7.3 kg). Evaluation at a student health center, including computed tomography (CT) of the brain, reportedly revealed no abnormalities. Three days before admission, photophobia, diplopia, neck stiffness, tremulousness of the left hand, and somnolence developed. On the day of admission, the patient became mute. Earlier that day, magnetic resonance imaging (MRI) of the brain and ...
C1 [Cho, Tracey A.; Chi, Andrew S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Schaefer, Pamela W.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Louis, David N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Cho, Tracey A.; Chi, Andrew S.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Schaefer, Pamela W.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Louis, David N.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Cho, TA (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
NR 17
TC 1
Z9 1
U1 1
U2 7
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 13
PY 2014
VL 370
IS 11
BP 1049
EP 1059
DI 10.1056/NEJMcpc1214216
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA AC7ED
UT WOS:000332689100013
PM 24620869
ER
PT J
AU Parikh, RB
Temel, JS
AF Parikh, Ravi B.
Temel, Jennifer S.
TI Early Specialty Palliative Care REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Parikh, Ravi B.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Temel, Jennifer S.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Parikh, RB (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA.
EM jtemel@partners.org
NR 4
TC 4
Z9 4
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 13
PY 2014
VL 370
IS 11
BP 1075
EP 1076
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA AC7ED
UT WOS:000332689100034
PM 24620886
ER
PT J
AU Ray, A
Boyer, D
Harris, NL
AF Ray, Alaka
Boyer, Daniel
Harris, Nancy Lee
TI Case 38-2013: A Man with Fever and Lymphadenopathy REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Ray, Alaka; Boyer, Daniel; Harris, Nancy Lee] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Ray, A (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 13
PY 2014
VL 370
IS 11
BP 1077
EP 1077
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA AC7ED
UT WOS:000332689100038
PM 24620889
ER
PT J
AU Lu, A
Magupalli, VG
Ruan, J
Yin, Q
Atianand, MK
Vos, MR
Schroder, GF
Fitzgerald, KA
Wu, H
Egelman, EH
AF Lu, Alvin
Magupalli, Venkat Giri
Ruan, Jianbin
Yin, Qian
Atianand, Maninjay K.
Vos, Matthijn R.
Schroeder, Gunnar F.
Fitzgerald, Katherine A.
Wu, Hao
Egelman, Edward H.
TI Unified Polymerization Mechanism for the Assembly of ASC-Dependent
Inflammasomes
SO CELL
LA English
DT Article
ID CRYSTAL-STRUCTURE; PYRIN DOMAIN; ELECTRON CRYOMICROSCOPY; AIM2
INFLAMMASOME; CRYO-EM; ACTIVATION; PROTEIN; DEATH; RESOLUTION;
OLIGOMERIZATION
AB Inflammasomes elicit host defense inside cells by activating caspase-1 for cytokine maturation and cell death. AIM2 and NLRP3 are representative sensor proteins in two major families of inflammasomes. The adaptor protein ASC bridges the sensor proteins and caspase-1 to form ternary inflammasome complexes, achieved through pyrin domain ( PYD) interactions between sensors and ASC and through caspase activation and recruitment domain ( CARD) interactions between ASC and caspase-1. We found that PYD and CARD both form filaments. Activated AIM2 and NLRP3 nucleate PYD filaments of ASC, which, in turn, cluster the CARD of ASC. ASC thus nucleates CARD filaments of caspase-1, leading to proximity-induced activation. Endogenous NLRP3 inflammasome is also filamentous. The cryoelectron microscopy structure of ASC(PYD) filament at near-atomic resolution provides a template for homo-and hetero-PYD/PYD associations, as confirmed by structure-guided mutagenesis. We propose that ASC-dependent inflammasomes in both families share a unified assembly mechanism that involves two successive steps of nucleation-induced polymerization.
C1 [Lu, Alvin; Magupalli, Venkat Giri; Ruan, Jianbin; Yin, Qian; Wu, Hao] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Lu, Alvin; Magupalli, Venkat Giri; Ruan, Jianbin; Yin, Qian; Wu, Hao] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Atianand, Maninjay K.; Fitzgerald, Katherine A.] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01655 USA.
[Vos, Matthijn R.] FEI Co, Nanoport Europe, NL-5651 GG Eindhoven, Netherlands.
[Schroeder, Gunnar F.] Forschungszentrum Julich, Inst Complex Syst, D-52425 Julich, Germany.
[Schroeder, Gunnar F.] Univ Dusseldorf, Dept Phys, D-40225 Dusseldorf, Germany.
[Egelman, Edward H.] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA.
RP Wu, H (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
EM hao.wu@childrens.harvard.edu
RI Schroder, Gunnar/H-5261-2013;
OI Schroder, Gunnar/0000-0003-1803-5431; Lu, Alvin/0000-0003-2353-848X;
Egelman, Edward/0000-0003-4844-5212; Ruan, Jianbin/0000-0001-5843-8273
FU National Institutes of Health [AI050872, EB001567, AI083713]
FX We thank Natacha Opalka, Seth Darst, Leona Cohen-Gould, Maria Ericsson,
William Rice, and Mariena Silvestry Ramos for help with EM imaging,
Harry Leung for help with confocal microscopy, Gabriel Nunez for
providing cDNAs, and the National Institutes of Health for funding
support (AI050872 to H.W., EB001567 to E.H.E., and AI083713 to K.A.F.).
NR 42
TC 182
Z9 188
U1 11
U2 50
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD MAR 13
PY 2014
VL 156
IS 6
BP 1193
EP 1206
DI 10.1016/j.cell.2014.02.008
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AD0ST
UT WOS:000332945100010
PM 24630722
ER
PT J
AU McFadden, DG
Papagiannakopoulos, T
Taylor-Weiner, A
Stewart, C
Carter, SL
Cibulskis, K
Bhutkar, A
McKenna, A
Dooley, A
Vernon, A
Sougnez, C
Malstrom, S
Heimann, M
Park, J
Chen, F
Farago, AF
Dayton, T
Shefler, E
Gabriel, S
Getz, G
Jacks, T
AF McFadden, David G.
Papagiannakopoulos, Thales
Taylor-Weiner, Amaro
Stewart, Chip
Carter, Scott L.
Cibulskis, Kristian
Bhutkar, Arjun
McKenna, Aaron
Dooley, Alison
Vernon, Amanda
Sougnez, Carrie
Malstrom, Scott
Heimann, Megan
Park, Jennifer
Chen, Frances
Farago, Anna F.
Dayton, Talya
Shefler, Erica
Gabriel, Stacey
Getz, Gad
Jacks, Tyler
TI Genetic and Clonal Dissection of Murine Small Cell Lung Carcinoma
Progression by Genome Sequencing
SO CELL
LA English
DT Article
ID TUMOR-SUPPRESSOR GENE; COPY-NUMBER ALTERATION; PANCREATIC-CANCER; MOUSE
MODEL; SOMATIC MUTATIONS; EVOLUTION; PTEN; HETEROGENEITY; INACTIVATION;
INSTABILITY
AB Small cell lung carcinoma (SCLC) is a highly lethal, smoking-associated cancer with few known targetable genetic alterations. Using genome sequencing, we characterized the somatic evolution of a genetically engineered mouse model (GEMM) of SCLC initiated by loss of Trp53 and Rb1. We identified alterations in DNA copy number and complex genomic rearrangements and demonstrated a low somatic point mutation frequency in the absence of tobacco mutagens. Alterations targeting the tumor suppressor Pten occurred in the majority of murine SCLC studied, and engineered Pten deletion accelerated murine SCLC and abrogated loss of Chr19 in Trp53; Rb1; Pten compound mutant tumors. Finally, we found evidence for polyclonal and sequential metastatic spread of murine SCLC by comparative sequencing of families of related primary tumors and metastases. We propose a temporal model of SCLC tumorigenesis with implications for human SCLC therapeutics and the nature of cancer-genome evolution in GEMMs.
C1 [McFadden, David G.; Papagiannakopoulos, Thales; Bhutkar, Arjun; Dooley, Alison; Vernon, Amanda; Malstrom, Scott; Heimann, Megan; Park, Jennifer; Chen, Frances; Farago, Anna F.; Dayton, Talya; Jacks, Tyler] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02142 USA.
[McFadden, David G.; Papagiannakopoulos, Thales; Bhutkar, Arjun; Dooley, Alison; Vernon, Amanda; Malstrom, Scott; Heimann, Megan; Park, Jennifer; Chen, Frances; Farago, Anna F.; Dayton, Talya; Jacks, Tyler] MIT, Dept Biol, Cambridge, MA 02142 USA.
[Jacks, Tyler] MIT, Howard Hughes Med Inst, Cambridge, MA 02142 USA.
[Taylor-Weiner, Amaro; Stewart, Chip; Carter, Scott L.; Cibulskis, Kristian; McKenna, Aaron; Sougnez, Carrie; Shefler, Erica; Gabriel, Stacey; Getz, Gad] Broad Inst MIT & Harvard, Canc Program, Cambridge, MA 02142 USA.
[Getz, Gad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Getz, Gad] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Getz, G (reprint author), Broad Inst MIT & Harvard, Canc Program, Cambridge, MA 02142 USA.
EM gadgetz@broadinstitute.org; tjacks@mit.edu
FU Ludwig Center for Molecular Oncology at MIT; Howard Hughes Medical
Institute; National Human Genome Research Institute; NIH-NCI Career
Development award [K08CA160658]; Hope Funds for Cancer Research
Fellowship
FX We acknowledge Denise Crowley and the Swanson Biotechnology Core
Facility for histology preparation and IHC; Harold Varmus, Nadya
Dimitrova, and Eric L. Snyder for critical review of the manuscript; and
Peter Campbell for a fruitful discussion. This work was supported by the
Ludwig Center for Molecular Oncology at MIT (to T.J.), the Howard Hughes
Medical Institute (to T.J.), the National Human Genome Research
Institute (to S. G. and G. G.), NIH-NCI Career Development award
K08CA160658 (to D. G. M.), and a Hope Funds for Cancer Research
Fellowship (to T. P.). G. G. is the Paul C. Zamecnik, MD, Chair in
Oncology at Massachusetts General Hospital. T.J. is the David H. Koch
Professor of Biology and a Daniel K. Ludwig Scholar at MIT. The authors
wish to dedicate this paper to the memory of Officer Sean Collier, for
his caring service to the MIT community and for his sacrifice.
NR 55
TC 72
Z9 75
U1 1
U2 21
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD MAR 13
PY 2014
VL 156
IS 6
BP 1298
EP 1311
DI 10.1016/j.cell.2014.02.031
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AD0ST
UT WOS:000332945100018
PM 24630729
ER
PT J
AU Rajbhandari, P
Schalper, KA
Solodin, NM
Ellison-Zelski, SJ
Lu, KP
Rimm, DL
Alarid, ET
AF Rajbhandari, P.
Schalper, K. A.
Solodin, N. M.
Ellison-Zelski, S. J.
Lu, K. Ping
Rimm, D. L.
Alarid, E. T.
TI Pin1 modulates ER alpha levels in breast cancer through inhibition of
phosphorylation-dependent ubiquitination and degradation
SO ONCOGENE
LA English
DT Article
DE breast cancer; E3 ligase; proteasome; survival
ID ESTROGEN-RECEPTOR-ALPHA; PROLYL ISOMERASE PIN1; GENE-EXPRESSION;
POSTTRANSLATIONAL MODIFICATIONS; TRANSCRIPTIONAL ACTIVATION;
SUBCELLULAR-LOCALIZATION; DIFFERENTIAL REGULATION; E6-ASSOCIATED
PROTEIN; TAMOXIFEN RESISTANCE; NUCLEAR RECEPTORS
AB Estrogen receptor-alpha (ER alpha) is an important biomarker used to classify and direct therapy decisions in breast cancer (BC). Both ER alpha protein and its transcript, ESR1, are used to predict response to tamoxifen therapy, yet certain tumors have discordant levels of ER alpha protein and ESR1, which is currently unexplained. Cellular ER alpha protein levels can be controlled post-translationally by the ubiquitin-proteasome pathway through a mechanism that depends on phosphorylation at residue S118. Phospho-S118 (pS118-ER alpha) is a substrate for the peptidyl prolyl isomerase, Pin1, which mediates cis-trans isomerization of the pS118-P119 bond to enhance ER alpha transcriptional function. Here, we demonstrate that Pin1 can increase ER alpha protein without affecting ESR1 transcript levels by inhibiting proteasome-dependent receptor degradation. Pin1 disrupts ER alpha ubiquitination by interfering with receptor interactions with the E3 ligase, E6AP, which also is shown to bind pS118-ER alpha. Quantitative in situ assessments of ER alpha protein, ESR1, and Pin1 in human tumors from a retrospective cohort show that Pin1 levels correlate with ER alpha protein but not to ESR1 levels. These data show that ER alpha protein is post-translationally regulated by Pin1 in a proportion of breast carcinomas. As Pin1 impacts both ER alpha protein levels and transactivation function, these data implicate Pin1 as a potential surrogate marker for predicting outcome of ER alpha-positive BC.
C1 [Rajbhandari, P.; Solodin, N. M.; Ellison-Zelski, S. J.; Alarid, E. T.] Univ Wisconsin, UW Carbone Comprehens Canc Ctr, Dept Oncol, Madison, WI 53705 USA.
[Schalper, K. A.; Rimm, D. L.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA.
[Lu, K. Ping] Harvard Univ, Sch Med, Dept Med, Canc Biol Program,Beth Isreal Deaconess Med Ctr, Boston, MA USA.
RP Rajbhandari, P (reprint author), Univ Wisconsin, UW Carbone Comprehens Canc Ctr, Dept Oncol, Wisconsin Inst Med Res 6151, Madison, WI 53705 USA.
EM alarid@oncology.wisc.edu
FU NIH [CA159578, T32 CA009135]; Genoptix/Novartis
FX We thank McArdle Laboratories for Cancer Research for support of this
project. We also thank the UW Carbone Comprehensive Cancer Center
(UWCCC) for use of its shared services to complete this research. We
thank Drs Pierre Chambon, Vladimir Spiegelman, Robert Kalejta and Greg
Finn for providing us appropriate expression plasmids and reagents. We
also thank Dr Wei Xu for insightful comments. This work was supported by
NIH grants CA159578 (to E.T.A.) and T32 CA009135 (to P.R.) and a
sponsored research award from Genoptix/Novartis (to D.R.).
NR 72
TC 16
Z9 18
U1 1
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD MAR 13
PY 2014
VL 33
IS 11
BP 1438
EP 1447
DI 10.1038/onc.2013.78
PG 10
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA AD0SD
UT WOS:000332943500011
PM 23542176
ER
PT J
AU Hoeppner, MP
Lundquist, A
Pirun, M
Meadows, JRS
Zamani, N
Johnson, J
Sundstrom, G
Cook, A
FitzGerald, MG
Swofford, R
Mauceli, E
Moghadam, BT
Greka, A
Alfoldi, J
Abouelleil, A
Aftuck, L
Bessette, D
Berlin, A
Brown, A
Gearin, G
Lui, A
Macdonald, JP
Priest, M
Shea, T
Turner-Maier, J
Zimmer, A
Lander, ES
di Palma, F
Lindblad-Toh, K
Grabherr, MG
AF Hoeppner, Marc P.
Lundquist, Andrew
Pirun, Mono
Meadows, Jennifer R. S.
Zamani, Neda
Johnson, Jeremy
Sundstrom, Gorel
Cook, April
FitzGerald, Michael G.
Swofford, Ross
Mauceli, Evan
Moghadam, Behrooz Torabi
Greka, Anna
Alfoeldi, Jessica
Abouelleil, Amr
Aftuck, Lynne
Bessette, Daniel
Berlin, Aaron
Brown, Adam
Gearin, Gary
Lui, Annie
Macdonald, J. Pendexter
Priest, Margaret
Shea, Terrance
Turner-Maier, Jason
Zimmer, Andrew
Lander, Eric S.
di Palma, Federica
Lindblad-Toh, Kerstin
Grabherr, Manfred G.
TI An Improved Canine Genome and a Comprehensive Catalogue of Coding Genes
and Non-Coding Transcripts
SO PLOS ONE
LA English
DT Article
ID WIDE ASSOCIATION; RNA-SEQ; SEQUENCE; DOG; CIS; DIFFERENTIATION;
IDENTIFICATION; DOMESTICATION; LANDSCAPE; COMPLEXES
AB The domestic dog, Canis familiaris, is a well-established model system for mapping trait and disease loci. While the original draft sequence was of good quality, gaps were abundant particularly in promoter regions of the genome, negatively impacting the annotation and study of candidate genes. Here, we present an improved genome build, canFam3.1, which includes 85 MB of novel sequence and now covers 99.8% of the euchromatic portion of the genome. We also present multiple RNA-Sequencing data sets from 10 different canine tissues to catalog similar to 175,000 expressed loci. While about 90% of the coding genes previously annotated by EnsEMBL have measurable expression in at least one sample, the number of transcript isoforms detected by our data expands the EnsEMBL annotations by a factor of four. Syntenic comparison with the human genome revealed an additional similar to 3,000 loci that are characterized as protein coding in human and were also expressed in the dog, suggesting that those were previously not annotated in the EnsEMBL canine gene set. In addition to,20,700 high-confidence protein coding loci, we found,4,600 antisense transcripts overlapping exons of protein coding genes, similar to 7,200 intergenic multi-exon transcripts without coding potential, likely candidates for long intergenic non-coding RNAs (lincRNAs) and,11,000 transcripts were reported by two different library construction methods but did not fit any of the above categories. Of the lincRNAs, about 6,000 have no annotated orthologs in human or mouse. Functional analysis of two novel transcripts with shRNA in a mouse kidney cell line altered cell morphology and motility. All in all, we provide a much-improved annotation of the canine genome and suggest regulatory functions for several of the novel non-coding transcripts.
C1 [Hoeppner, Marc P.; Meadows, Jennifer R. S.; Zamani, Neda; Sundstrom, Gorel; Lindblad-Toh, Kerstin; Grabherr, Manfred G.] Uppsala Univ, Dept Med Biochem & Microbiol, Sci Life Labs, Uppsala, Sweden.
[Lundquist, Andrew; Johnson, Jeremy; Cook, April; FitzGerald, Michael G.; Swofford, Ross; Greka, Anna; Alfoeldi, Jessica; Abouelleil, Amr; Aftuck, Lynne; Bessette, Daniel; Berlin, Aaron; Brown, Adam; Gearin, Gary; Lui, Annie; Macdonald, J. Pendexter; Priest, Margaret; Shea, Terrance; Turner-Maier, Jason; Zimmer, Andrew; Lander, Eric S.; di Palma, Federica; Lindblad-Toh, Kerstin; Grabherr, Manfred G.] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Lundquist, Andrew] Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA USA.
[Lundquist, Andrew] Harvard Univ, Sch Med, Charlestown, MA USA.
[Pirun, Mono] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Mauceli, Evan] Boston Childrens Hosp, Boston, MA USA.
[Moghadam, Behrooz Torabi] Uppsala Univ, Dept Cell & Mol Biol, Uppsala, Sweden.
[di Palma, Federica] Genome Anal Ctr, Norwich, Norfolk, England.
RP Lindblad-Toh, K (reprint author), Uppsala Univ, Dept Med Biochem & Microbiol, Sci Life Labs, Uppsala, Sweden.
EM kersli@broadinstitute.org; manfred.grabherr@imbim.uu.se
FU NHGRI [U54 HG003067]; Uppsala University; Swedish Medical Research
Council; Research Council FORMAS; European Commission [FP7-LUPA,
GA-201370]; Science for Life Laboratory
FX This work was funded in part by NHGRI (U54 HG003067), Uppsala
University, Swedish Medical Research Council, Research Council FORMAS,
and the European Commission (FP7-LUPA, GA-201370), and a start-up grant
from the Science for Life Laboratory to MGG. KLT is a recipient of a
EURYI from the ESF and received a Consolidator Award from ERC. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 50
TC 40
Z9 40
U1 2
U2 24
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 13
PY 2014
VL 9
IS 3
AR e91172
DI 10.1371/journal.pone.0091172
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC9JS
UT WOS:000332851300061
PM 24625832
ER
PT J
AU Zhang, GL
Riemer, AB
Keskin, DB
Chitkushev, L
Reinherz, EL
Brusic, V
AF Zhang, Guang Lan
Riemer, Angelika B.
Keskin, Derin B.
Chitkushev, Lou
Reinherz, Ellis L.
Brusic, Vladimir
TI HPVdb: a data mining system for knowledge discovery in human
papillomavirus with applications in T cell immunology and vaccinology
SO DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION
LA English
DT Article
ID BINDING PREDICTION SERVERS; INVASIVE CERVICAL-CANCER; VACCINATION;
CLASSIFICATION; ONCOPROTEINS; RECOMBINANT; WORLDWIDE; PEPTIDES; TYPE-16;
TOOL
AB High-risk human papillomaviruses (HPVs) are the causes of many cancers, including cervical, anal, vulvar, vaginal, penile and oropharyngeal. To facilitate diagnosis, prognosis and characterization of these cancers, it is necessary to make full use of the immunological data on HPV available through publications, technical reports and databases. These data vary in granularity, quality and complexity. The extraction of knowledge from the vast amount of immunological data using data mining techniques remains a challenging task. To support integration of data and knowledge in virology and vaccinology, we developed a framework called KB-builder to streamline the development and deployment of web-accessible immunological knowledge systems. The framework consists of seven major functional modules, each facilitating a specific aspect of the knowledge-base construction process. Using KB-builder, we constructed the Human Papillomavirus T cell Antigen Database (HPVdb). It contains 2781 curated antigen entries of antigenic proteins derived from 18 genotypes of high-risk HPV and 18 genotypes of low-risk HPV. The HPVdb also catalogs 191 verified T cell epitopes and 45 verified human leukocyte antigen (HLA) ligands. Primary amino acid sequences of HPV antigens were collected and annotated from the UniProtKB. T cell epitopes and HLA ligands were collected from data mining of scientific literature and databases. The data were subject to extensive quality control (redundancy elimination, error detection and vocabulary consolidation). A set of computational tools for an in-depth analysis, such as sequence comparison using BLAST search, multiple alignments of antigens, classification of HPV types based on cancer risk, T cell epitope/HLA ligand visualization, T cell epitope/HLA ligand conservation analysis and sequence variability analysis, has been integrated within the HPVdb. Predicted Class I and Class II HLA binding peptides for 15 common HLA alleles are included in this database as putative targets. HPVdb is a knowledge-based system that integrates curated data and information with tailored analysis tools to facilitate data mining for HPV vaccinology and immunology. To our best knowledge, HPVdb is a unique data source providing a comprehensive list of HPV antigens and peptides.
C1 [Zhang, Guang Lan; Keskin, Derin B.; Reinherz, Ellis L.; Brusic, Vladimir] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA.
[Zhang, Guang Lan; Chitkushev, Lou; Brusic, Vladimir] Boston Univ, Dept Comp Sci, Metropolitan Coll, Boston, MA 02215 USA.
[Zhang, Guang Lan; Keskin, Derin B.; Reinherz, Ellis L.; Brusic, Vladimir] Harvard Univ, Dept Med, Sch Med, Boston, MA 02115 USA.
[Riemer, Angelika B.] German Canc Res Ctr, D-69120 Heidelberg, Germany.
RP Zhang, GL (reprint author), Dana Farber Canc Inst, Canc Vaccine Ctr, 77 Ave Louis Pasteur, Boston, MA 02115 USA.
EM guanglan@bu.edu; vladimir_brusic@dfci.harvard.edu
FU NIH [UO1 AI090043]
FX Funding for open access charge: NIH grant UO1 AI090043.
NR 35
TC 6
Z9 6
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1758-0463
J9 DATABASE-OXFORD
JI Database
PD MAR 12
PY 2014
AR bau031
DI 10.1093/database/bau031
PG 12
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA AO9UL
UT WOS:000341703500001
ER
PT J
AU Sears, CL
Garrett, WS
AF Sears, Cynthia L.
Garrett, Wendy S.
TI Microbes, Microbiota, and Colon Cancer
SO CELL HOST & MICROBE
LA English
DT Review
ID HUMAN GUT MICROBIOME; ENTEROTOXIGENIC BACTEROIDES-FRAGILIS;
STREPTOCOCCUS-GALLOLYTICUS INFECTION; BETA-GLUCURONIDASE INHIBITION;
NF-KAPPA-B; COLORECTAL-CANCER; ESCHERICHIA-COLI; TUMOR MICROENVIRONMENT;
URSODEOXYCHOLIC ACID; COMMENSAL BACTERIA
AB Colorectal cancer (CRC) presents a considerable disease burden worldwide. The human colon is also an anatomical location with the largest number of microbes. It is natural, therefore, to anticipate a role for microbes, particularly bacteria, in colorectal carcinogenesis. The increasing accessibility of microbial meta'omics is fueling a surge in our understanding of the role that microbes and the microbiota play in CRC. In this review, we will discuss recent insights into contributions of the microbiota to CRC and explore conceptual frameworks for evaluating the role of microbes in cancer causation. We also highlight new findings on candidate CRC-potentiating species and current knowledge gaps. Finally, we explore the roles of microbial metabolism as it relates to bile acids, xenobiotics, and diet in the etiology and therapeutics of CRC.
C1 [Sears, Cynthia L.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Sears, Cynthia L.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.
[Sears, Cynthia L.] Johns Hopkins Univ, Sch Med, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA.
[Sears, Cynthia L.] Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Garrett, Wendy S.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Garrett, Wendy S.] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA.
[Garrett, Wendy S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Garrett, Wendy S.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Garrett, Wendy S.] Broad Inst Harvard, Cambridge, MA 02142 USA.
[Garrett, Wendy S.] MIT, Cambridge, MA 02142 USA.
RP Sears, CL (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
EM csears@jhmi.edu; wgarrett@hsph.harvard.edu
FU NIH [R01CA151393, R21CA170492, R01CA151325, R01CA179440, R01CA154426,
K08AI078942]; Merieux Institute; Wellcome Career in Medical Sciences
Award; Searle Scholars Award; Cancer Research Institute Investigator
Award
FX We thank current and former members of the Sears and Garrett labs.
C.L.S. also thanks Drew Pardoll, Ken Kinzler, Bert Vogelstein, and
members of their groups for helpful discussions over time; W.S.G. also
thanks Aleksandar D. Kostic, Andrew T. Chan, and Curtis Huttenhower for
thoughtful discussions. C.L.S. acknowledges the following funding
sources: NIH (R01CA151393, R21CA170492, R01CA151325, R01CA179440) and
the Merieux Institute. W.S.G. acknowledges the following funding
sources: NIH (R01CA154426 and K08AI078942), a Burroughs Wellcome Career
in Medical Sciences Award, a Searle Scholars Award, and a Cancer
Research Institute Investigator Award.
NR 90
TC 115
Z9 124
U1 18
U2 108
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
EI 1934-6069
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD MAR 12
PY 2014
VL 15
IS 3
BP 317
EP 328
DI 10.1016/j.chom.2014.02.007
PG 12
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AD2WZ
UT WOS:000333098600010
PM 24629338
ER
PT J
AU Gevers, D
Kugathasan, S
Denson, LA
Vazquez-Baeza, Y
Van Treuren, W
Ren, BY
Schwager, E
Knights, D
Song, SJ
Yassour, M
Morgan, XC
Kostic, AD
Luo, CW
Gonzalez, A
McDonald, D
Haberman, Y
Walters, T
Baker, S
Rosh, J
Stephens, M
Heyman, M
Markowitz, J
Baldassano, R
Griffiths, A
Sylvester, F
Mack, D
Kim, S
Crandall, W
Hyams, J
Huttenhower, C
Knight, R
Xavier, RJ
AF Gevers, Dirk
Kugathasan, Subra
Denson, Lee A.
Vazquez-Baeza, Yoshiki
Van Treuren, Will
Ren, Boyu
Schwager, Emma
Knights, Dan
Song, Se Jin
Yassour, Moran
Morgan, Xochitl C.
Kostic, Aleksandar D.
Luo, Chengwei
Gonzalez, Antonio
McDonald, Daniel
Haberman, Yael
Walters, Thomas
Baker, Susan
Rosh, Joel
Stephens, Michael
Heyman, Melvin
Markowitz, James
Baldassano, Robert
Griffiths, Anne
Sylvester, Francisco
Mack, David
Kim, Sandra
Crandall, Wallace
Hyams, Jeffrey
Huttenhower, Curtis
Knight, Rob
Xavier, Ramnik J.
TI The Treatment-Naive Microbiome in New-Onset Crohn's Disease
SO CELL HOST & MICROBE
LA English
DT Article
ID INFLAMMATORY-BOWEL-DISEASE; GUT MICROBIOME; TRANSPLANTATION;
PATHOGENESIS; BACTERIA; CELLS
AB Inflammatory bowel diseases (IBDs), including Crohn's disease (CD), are genetically linked to host pathways that implicate an underlying role for aberrant immune responses to intestinal microbiota. However, patterns of gut microbiome dysbiosis in IBD patients are inconsistent among published studies. Using samples from multiple gastrointestinal locations collected prior to treatment in new-onset cases, we studied the microbiome in the largest pediatric CD cohort to date. An axis defined by an increased abundance in bacteria which include Enterobacteriaceae, Pasteurellacaea, Veillonellaceae, and Fusobacteriaceae, and decreased abundance in Erysipelotrichales, Bacteroidales, and Clostridiales, correlates strongly with disease status. Microbiome comparison between CD patients with and without antibiotic exposure indicates that antibiotic use amplifies the microbial dysbiosis associated with CD. Comparing the microbial signatures between the ileum, the rectum, and fecal samples indicates that at this early stage of disease, assessing the rectal mucosal-associated microbiome offers unique potential for convenient and early diagnosis of CD.
C1 [Gevers, Dirk; Yassour, Moran; Kostic, Aleksandar D.; Luo, Chengwei; Huttenhower, Curtis; Xavier, Ramnik J.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
[Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA.
[Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
[Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Kugathasan, Subra] Emory Univ, Dept Pediat, Div Gastroenterol Hepatol & Nutr, Atlanta, GA 30322 USA.
[Denson, Lee A.; Haberman, Yael] Cincinnati Childrens Hosp, Med Ctr, Div Gastroenterol Hepatol & Nutr, Cincinnati, OH 45229 USA.
[Vazquez-Baeza, Yoshiki] Univ Colorado, Dept Comp Sci, Boulder, CO 80309 USA.
[Van Treuren, Will; Song, Se Jin; Gonzalez, Antonio; McDonald, Daniel; Knight, Rob] Univ Colorado, BioFrontiers Inst, Boulder, CO 80309 USA.
[Ren, Boyu; Schwager, Emma; Morgan, Xochitl C.; Huttenhower, Curtis] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Knights, Dan] Univ Minnesota, Dept Comp Sci & Engn, Minneapolis, MN 55108 USA.
[Knights, Dan] Univ Minnesota, Inst Biotechnol, St Paul, MN 55108 USA.
[Walters, Thomas] Univ Toronto, Hosp Sick Children, Div Gastroenterol Hepatol & Nutr, Toronto, ON M5G IX8, Canada.
[Baker, Susan] Childrens Hosp Buffalo, Buffalo, NY 14222 USA.
[Rosh, Joel] Goryeb Childrens Hosp, Morristown, NJ 07960 USA.
[Stephens, Michael] Mayo Clin, Rochester, MN 55902 USA.
[Heyman, Melvin] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Markowitz, James] North Shore Long Isl Jewish Med Ctr, New Hyde Pk, NY 11040 USA.
[Baldassano, Robert] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Griffiths, Anne] Hosp Sick Children, Toronto, ON M5G IX8, Canada.
[Sylvester, Francisco; Hyams, Jeffrey] Connecticut Childrens Med Ctr, Hartford, CT 06106 USA.
[Mack, David] Childrens Hosp Eastern Ontario, Ottawa, ON K1H 8L1, Canada.
[Kim, Sandra; Crandall, Wallace] Nationwide Childrens Hosp, Columbus, OH 43228 USA.
[Knight, Rob] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA.
[Knight, Rob] Howard Hughes Med Inst, Boulder, CO 80309 USA.
RP Xavier, RJ (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
EM xavier@molbio.mgh.harvard.edu
RI Crandall, Wallace/E-2928-2011; Knight, Rob/D-1299-2010
OI Morgan, Xochitl/0000-0002-6264-6961; Kostic,
Aleksandar/0000-0002-0837-4360;
FU Crohn's and Colitis Foundation of America; Leona M. and Harry B.
Helmsley Charitable Trust; ARO [W911NF-11-1-0473]; NIH [U54 DE023798,
R01 HG005969, R01 DK092405]
FX We thank the patients who donated samples for this study, the health
professionals who collected them, and the Crohn's and Colitis Foundation
of America for supporting the RISK cohort. We thank Douglas Wendel, Gail
Ackermann, Tim Vigers, and Tim L. Tickle for their valuable input and
helpful discussions. We thank participating clinicians Marla Dubinsky,
Joshua Noe, Scott Snapper, Richard Kellermayer, Michael Kappleman,
Anthony Otley, Mirian Pfefferkorn, Stanley Cohen, Stephen Guthery, Neal
LeLeiko, Maria Oliva-Hemker, David Keljo, Dedrick Moulton, Barbara
Kircshner, Ashish Patel, David Ziring, Jonathan Evans, Jonah Essers,
Bruce Aronow, and MiOk Kim. Work was supported by grants from the
Crohn's and Colitis Foundation of America, The Leona M. and Harry B.
Helmsley Charitable Trust, ARO grant W911NF-11-1-0473 (C.H.), and by NIH
grants U54 DE023798, R01 HG005969 (C.H.), and R01 DK092405 (R.J.X.,
C.H., and D.G.).
NR 40
TC 382
Z9 389
U1 29
U2 129
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
EI 1934-6069
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD MAR 12
PY 2014
VL 15
IS 3
BP 382
EP 392
DI 10.1016/j.chom.2014.02.005
PG 11
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AD2WZ
UT WOS:000333098600016
PM 24629344
ER
PT J
AU Hashmi, JA
Kong, J
Spaeth, R
Khan, S
Kaptchuk, TJ
Gollub, RL
AF Hashmi, Javeria Ali
Kong, Jian
Spaeth, Rosa
Khan, Sheraz
Kaptchuk, Ted J.
Gollub, Randy L.
TI Functional Network Architecture Predicts Psychologically Mediated
Analgesia Related to Treatment in Chronic Knee Pain Patients
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE brain network; chronic pain; placebo; predictive analysis; resting
state; synchronization
ID PLACEBO ANALGESIA; BRAIN NETWORKS; NEUROBIOLOGICAL MECHANISMS;
INDIVIDUAL-DIFFERENCES; ACUPUNCTURE TREATMENT; INDUCED EXPECTATIONS;
PREFRONTAL CORTEX; BACK-PAIN; CONNECTIVITY; ANTICIPATION
AB Placebo analgesia is an indicator of how efficiently the brain translates psychological signals conveyed by a treatment procedure into pain relief. It has been demonstrated that functional connectivity between distributed brain regions predicts placebo analgesia in chronic back pain patients. Greater network efficiency in baseline brain networks may allow better information transfer and facilitate adaptive physiological responses to psychological aspects of treatment. Here, we theorized that topological network alignments in resting state scans predict psychologically conditioned analgesic responses to acupuncture treatment in chronic knee osteoarthritis pain patients (n = 45). Analgesia was induced by building positive expectations toward acupuncture treatment with verbal suggestion and heat pain conditioning on a test site of the arm. This procedure induced significantly more analgesia after sham or real acupuncture on the test site than in a control site. The psychologically conditioned analgesia was invariant to sham versus real treatment. Efficiency of information transfer within local networks calculated with graph-theoretic measures (local efficiency and clustering coefficients) significantly predicted conditioned analgesia. Clustering coefficients in regions associated with memory, motivation, and pain modulation were closely involved in predicting analgesia. Moreover, women showed higher clustering coefficients and marginally greater pain reduction than men. Overall, analgesic response to placebo cues can be predicted from a priori resting state data by observing local network topology. Such low-cost synchronizations may represent preparatory resources that facilitate subsequent performance of brain circuits in responding to adaptive environmental cues. This suggests a potential utility of network measures in predicting placebo response for clinical use.
C1 [Hashmi, Javeria Ali; Kong, Jian; Spaeth, Rosa; Gollub, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA.
[Hashmi, Javeria Ali; Kong, Jian; Khan, Sheraz] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Khan, Sheraz] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA.
[Hashmi, Javeria Ali; Kong, Jian; Khan, Sheraz; Gollub, Randy L.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA.
[Khan, Sheraz] MIT, Cambridge, MA 02139 USA.
[Kaptchuk, Ted J.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Program Placebo Studies, Boston, MA 02215 USA.
RP Hashmi, JA (reprint author), 120 Second Ave,Suite 103, Charlestown, MA 02129 USA.
EM javeria.hashmi@utoronto.ca; rgollub@partners.org
OI Gollub, Randy L./0000-0002-9434-4044; Khan, Sheraz/0000-0002-6792-3577
FU Nancy Lurie Marks Family Foundation; [R01AT005280]; [R01AT006364];
[P01-AT002048]
FX Funding and support for this study came from R01AT005280 (R.L.G. and
T.J.K.), R01AT006364 (J.K.), and P01-AT002048 to Bruce Rosen
(Massachusetts General Hospital, Charlestown, MA). S.K. is funded by
Nancy Lurie Marks Family Foundation Fellowship. We thank Irving Kirsch
and Mark Vangel for their valuable suggestions and comments.
NR 76
TC 14
Z9 15
U1 2
U2 22
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAR 12
PY 2014
VL 34
IS 11
BP 3924
EP 3936
DI 10.1523/JNEUROSCI.3155-13.2014
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA AC9UG
UT WOS:000332879500012
PM 24623770
ER
PT J
AU Cha, J
Greenberg, T
Carlson, JM
DeDora, DJ
Hajcak, G
Mujica-Parodi, LR
AF Cha, Jiook
Greenberg, Tsafrir
Carlson, Joshua M.
DeDora, Daniel J.
Hajcak, Greg
Mujica-Parodi, Lilianne R.
TI Circuit-Wide Structural and Functional Measures Predict Ventromedial
Prefrontal Cortex Fear Generalization: Implications for Generalized
Anxiety Disorder
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE anxiety; fear conditioning; connectivity; tractography; resting-state;
fear generalizaton
ID TRAIT ANXIETY; SEROTONIN TRANSPORTER; CONDITIONED FEAR;
INDIVIDUAL-DIFFERENCES; POLYMORPHISM 5-HTTLPR; MEDIODORSAL THALAMUS;
EXTINCTION MEMORY; AMYGDALA; CONNECTIVITY; HUMANS
AB The ventromedial prefrontal cortex (vmPFC) plays a critical role in a number of evaluative processes, including risk assessment. Impaired discrimination between threat and safety is considered a hallmark of clinical anxiety. Here, we investigated the circuit-wide structural and functional mechanisms underlying vmPFC threat-safety assessment in humans. We tested patients with generalized anxiety disorder (GAD; n = 32, female) and healthy controls (n = 25, age-matched female) on a task that assessed the generalization of conditioned threat during fMRI scanning. The task consisted of seven rectangles of graded widths presented on a screen; only the midsize one was paired with mild electric shock [conditioned stimulus (CS)], while the others, safety cues, systematically varied in width by +/- 20, 40, and 60% [generalization stimuli (GS)] compared with the CS. We derived an index reflecting vmPFC functioning from the BOLD reactivity on a continuum of threat (CS) to safety (GS least similar to CS); patients with GAD showed less discrimination between threat and safety cues, compared with healthy controls (Greenberg et al., 2013b). Using structural, functional (i.e., resting-state), and diffusion MRI, we measured vmPFC thickness, vmPFC functional connectivity, and vmPFC structural connectivity within the corticolimbic systems. The results demonstrate that all three factors predict individual variability of vmPFC threat assessment in an independent fashion. Moreover, these neural features are also linked to GAD, most likely via an vmPFC fear generalization. Our results strongly suggest that vmPFC threat processing is closely associated with broader corticolimbic circuit anomalies, which may synergistically contribute to clinical anxiety.
C1 [Cha, Jiook; Mujica-Parodi, Lilianne R.] SUNY Stony Brook, Program Neurosci, Stony Brook, NY 11794 USA.
[Greenberg, Tsafrir; Hajcak, Greg] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA.
[Carlson, Joshua M.; DeDora, Daniel J.; Mujica-Parodi, Lilianne R.] SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA.
[Carlson, Joshua M.] No Michigan Univ, Dept Psychol, Marquette, MI 49855 USA.
[Mujica-Parodi, Lilianne R.] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
RP Mujica-Parodi, LR (reprint author), SUNY Stony Brook, Lab Computat Neurodiag, Dept Biomed Engn, Bioengn Bldg Room 119,100 Nicolls Rd, Stony Brook, NY 11794 USA.
EM Lilianne.strey@stonybrook.edu
RI Cha, Jiook/A-5678-2013; Greenberg, Tsafrir /Q-7831-2016;
OI Cha, Jiook/0000-0002-5314-7992; Mujica-Parodi,
Lilianne/0000-0002-3752-5519
FU Office of Naval Research [N0014-04-1-005]; National Science Foundation
[0954643]
FX This work was supported by function from the Office of Naval Research (#
N0014-04-1-005, to L.R. M.-P.) and the National Science Foundation (#
0954643, to L.R. M.-P.).
NR 53
TC 25
Z9 26
U1 3
U2 24
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAR 12
PY 2014
VL 34
IS 11
BP 4043
EP 4053
DI 10.1523/JNEUROSCI.3372-13.2014
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA AC9UG
UT WOS:000332879500023
PM 24623781
ER
PT J
AU Das, S
McCaffrey, PG
Talkington, MWT
Andrews, NA
Corlosquet, S
Ivinson, AJ
Clark, T
AF Das, Sudeshna
McCaffrey, Patricia G.
Talkington, Megan W. T.
Andrews, Neil A.
Corlosquet, Stephane
Ivinson, Adrian J.
Clark, Tim
TI Pain Research Forum: application of scientific social media frameworks
in neuroscience
SO FRONTIERS IN NEUROINFORMATICS
LA English
DT Article
DE social media; neuropathic pain; content management systems; Drupal
ID WEB COMMUNITIES; SCIENCE; COLLABORATORIES; ALZFORUM
AB Background: Social media has the potential to accelerate the pace of biomedical research through online collaboration, discussions, and faster sharing of information. Focused web-based scientific social collaboratories such as the Alzheimer Research Forum have been successful in engaging scientists in open discussions of the latest research and identifying gaps in knowledge. However, until recently, tools to rapidly create such communities and provide high-bandwidth information exchange between collaboratories in related fields did not exist.
Methods: We have addressed this need by constructing a reusable framework to build online biomedical communities, based on Drupal, an open-source content management system. The framework incorporates elements of Semantic Web technology combined with social media. Here we present, as an exemplar of a web community built on our framework, the Pain Research Forum (PRF) (hftp://painresearchforum.org). PRF is a community of chronic pain researchers, established with the goal of fostering collaboration and communication among pain researchers.
Results: Launched in 2011, PRF has over 1300 registered members with permission to submit content. It currently hosts over 150 topical news articles on research; more than 30 active or archived forum discussions and journal club features; a webinar series; an editor-curated weekly updated listing of relevant papers; and several other resources for the pain research community. All content is licensed for reuse under a Creative Commons license; the software is freely available. The framework was reused to develop other sites, notably the Multiple Sclerosis Discovery Forum (hftp://msdiscovery.org) and StemBook (hftp://stembook.org).
Discussion: Web-based collaboratories are a crucial integrative tool supporting rapid information transmission and translation in several important research areas. In this article, we discuss the success factors, lessons learned, and ongoing challenges in using PRF as a driving force to develop tools for online collaboration in neuroscience. We also indicate ways these tools can be applied to other areas and uses.
C1 [Das, Sudeshna; Ivinson, Adrian J.; Clark, Tim] MIT, Massachusetts Gen Hosp, Inst Neurodegenerat Dis, Cambridge, MA 02139 USA.
[Das, Sudeshna; Clark, Tim] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[McCaffrey, Patricia G.; Talkington, Megan W. T.; Andrews, Neil A.; Ivinson, Adrian J.] Harvard Univ, Sch Med, Harvard NeuroDiscovery Ctr, Boston, MA 02115 USA.
[Clark, Tim] Univ Manchester, Sch Comp Sci, Manchester, Lancs, England.
RP Das, S (reprint author), MIT, Massachusetts Gen Hosp, Inst Neurodegenerat Dis, 65 Landsdowne St, Cambridge, MA 02139 USA.
EM sdas5@mgh.harvard.edu
OI Clark, Timothy/0000-0003-4060-7360
FU Curvey Family Foundation; Mayday Fund; Guthart Family Foundation; Purdue
Pharma L.P.; Genentech
FX We gratefully acknowledge essential funding from the Curvey Family
Foundation, the Mayday Fund, the Guthart Family Foundation, Purdue
Pharma L.P. and Genentech. We thank Alzforum and PDOnline editors for
their feedback and ideas, Nick Maloney, Paul Northup, Jake Strawn, and
Chris Akeley for their contributions to software development, and
Stoltze Design for graphic design.
NR 25
TC 2
Z9 2
U1 0
U2 13
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5196
J9 FRONT NEUROINFORM
JI Front. Neuroinformatics
PD MAR 11
PY 2014
VL 8
AR 21
DI 10.3389/fninf.2014.00021
PG 13
WC Mathematical & Computational Biology; Neurosciences
SC Mathematical & Computational Biology; Neurosciences & Neurology
GA AZ3DA
UT WOS:000348106700001
PM 24653693
ER
PT J
AU Mackin, RS
Insel, P
Truran, D
Vichinsky, EP
Neumayr, LD
Armstrong, FD
Gold, JI
Kesler, K
Brewer, J
Weiner, MW
AF Mackin, R. Scott
Insel, Philip
Truran, Diana
Vichinsky, Elliot P.
Neumayr, Lynne D.
Armstrong, F. D.
Gold, Jeffrey I.
Kesler, Karen
Brewer, Joseph
Weiner, Michael W.
CA Neuropsychological Dysfunction Neu
TI Neuroimaging abnormalities in adults with sickle cell anemia
Associations with cognition
SO NEUROLOGY
LA English
DT Article
ID HUMAN CEREBRAL-CORTEX; CORTICAL THICKNESS; BIOLOGICAL MARKERS; BASAL
GANGLIA; RISK-FACTORS; GRAY-MATTER; BACK-PAIN; DISEASE; CHILDREN; BRAIN
AB Objective:This study was conducted to determine the relationship of frontal lobe cortical thickness and basal ganglia volumes to measures of cognition in adults with sickle cell anemia (SCA).Methods:Participants included 120 adults with SCA with no history of neurologic dysfunction and 33 healthy controls (HCs). Participants were enrolled at 12 medical center sites, and raters were blinded to diagnostic group. We hypothesized that individuals with SCA would exhibit reductions in frontal lobe cortex thickness and reduced basal ganglia and thalamus volumes compared with HCs and that these structural brain abnormalities would be associated with measures of cognitive functioning (Wechsler Adult Intelligence Scale, 3rd edition).Results:After adjusting for age, sex, education level, and intracranial volume, participants with SCA exhibited thinner frontal lobe cortex (t = -2.99, p = 0.003) and reduced basal ganglia and thalamus volumes compared with HCs (t = -3.95, p < 0.001). Reduced volume of the basal ganglia and thalamus was significantly associated with lower Performance IQ (model estimate = 3.75, p = 0.004) as well as lower Perceptual Organization (model estimate = 1.44, p = 0.007) and Working Memory scores (model estimate = 1.37, p = 0.015). Frontal lobe cortex thickness was not significantly associated with any cognitive measures.Conclusions:Our findings suggest that basal ganglia and thalamus abnormalities may represent a particularly salient contributor to cognitive dysfunction in adults with SCA.
C1 [Mackin, R. Scott] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
[Mackin, R. Scott; Insel, Philip; Truran, Diana; Brewer, Joseph; Weiner, Michael W.] San Francisco Vet Adm Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA.
[Vichinsky, Elliot P.; Neumayr, Lynne D.] Childrens Hosp & Res Ctr Oakland, Dept Hematol Oncol, Oakland, CA 94609 USA.
[Gold, Jeffrey I.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90089 USA.
[Gold, Jeffrey I.] Childrens Hosp Los Angeles, Dept Anesthesiol, Los Angeles, CA 90027 USA.
[Gold, Jeffrey I.] Childrens Hosp Los Angeles, Dept Pediat, Los Angeles, CA 90027 USA.
[Kesler, Karen] Rho Inc, Res Triangle Pk, NC USA.
[Armstrong, F. D.] Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33136 USA.
[Armstrong, F. D.] Holtz Childrens Hosp, Miami, FL USA.
[Weiner, Michael W.] Univ Calif San Francisco, Vet Adm Med Ctr, San Francisco, CA USA.
[Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA.
[Weiner, Michael W.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Weiner, Michael W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Weiner, Michael W.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
RP Mackin, RS (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
EM scottm@lppi.ucsf.edu
FU National Heart, Lung, and Blood Institute [U54HL070587]; National
Institute of Mental Health [K08MH081065]
FX Supported by the National Heart, Lung, and Blood Institute (U54HL070587)
and the National Institute of Mental Health (K08MH081065).
NR 40
TC 14
Z9 14
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD MAR 11
PY 2014
VL 82
IS 10
BP 835
EP 841
DI 10.1212/WNL.0000000000000188
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA AH9TJ
UT WOS:000336485100008
PM 24523480
ER
PT J
AU Rosas, HD
Doros, G
Gevorkian, S
Malarick, K
Reuter, M
Coutu, JP
Triggs, TD
Wilkens, PJ
Matson, W
Salat, DH
Hersch, SM
AF Rosas, Herminia D.
Doros, Gheorghe
Gevorkian, Sona
Malarick, Keith
Reuter, Martin
Coutu, Jean-Philippe
Triggs, Tyler D.
Wilkens, Paul J.
Matson, Wayne
Salat, David H.
Hersch, Steven M.
TI PRECREST: A phase II prevention and biomarker trial of creatine in
at-risk Huntington disease
SO NEUROLOGY
LA English
DT Article
ID EPISODIC MEMORY; PREMANIFEST; PROGRESSION; DIAGNOSIS; COGNITION; 8OHDG;
HD
AB Objective:To assess the safety and tolerability of high-dose creatine, the feasibility of enrolling premanifest and 50% at-risk subjects in a prevention trial, and the potential of cognitive, imaging, and blood markers.Methods:Sixty-four eligible consenting participants were randomly allocated (1:1) to 15 g twice daily of creatine monohydrate or placebo for a 6-month double-blind phase followed by a 12-month open-label extension. Subjects included premanifest (tested) and at-risk (not tested) individuals without clinical symptoms or signs of Huntington disease (HD). Primary outcomes were safety and tolerability. Exploratory endpoints included fine motor, visuospatial, and memory performance; structural and diffusion MRI; and selected blood markers.Results:Forty-seven HD carriers and 17 non-HD controls were enrolled. Fifteen discontinued treatment (2 assigned to placebo); all were followed for the entire study period. Primary analysis was by intent to treat. The most common adverse events were gastrointestinal. Neuroimaging demonstrated treatment-related slowing of cortical and striatal atrophy at 6 and 18 months.Conclusion:We describe a design that preserves the autonomy of subjects not wanting genetic testing while including controls for assessing the specificity of treatment effects. Our results demonstrate the feasibility of prevention trials for HD and the safety of high-dose creatine, provide possible evidence of disease modification, support future studies of creatine, and illustrate the value of prodromal biomarkers.Classification of evidence:This study provides Class I evidence that high-dose creatine is safe and tolerable.
C1 [Rosas, Herminia D.; Gevorkian, Sona; Malarick, Keith; Reuter, Martin; Triggs, Tyler D.; Wilkens, Paul J.; Hersch, Steven M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Rosas, Herminia D.; Gevorkian, Sona; Malarick, Keith; Reuter, Martin; Coutu, Jean-Philippe; Triggs, Tyler D.; Wilkens, Paul J.; Salat, David H.] Massachusetts Gen Hosp, Ctr Neuroimaging Aging & Neurodegenerat Dis, Boston, MA 02114 USA.
[Rosas, Herminia D.; Gevorkian, Sona; Malarick, Keith; Reuter, Martin; Triggs, Tyler D.; Wilkens, Paul J.; Salat, David H.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
[Rosas, Herminia D.; Reuter, Martin] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
[Doros, Gheorghe] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Coutu, Jean-Philippe] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA.
[Matson, Wayne] New England Vet Adm, Geriatr Res Educ Clin Ctr, Bedford, MA USA.
RP Rosas, HD (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
EM rosas@helix.mgh.harvard.edu
RI Reuter, Martin/B-3456-2010;
OI Reuter, Martin/0000-0002-2665-9693; /0000-0003-4895-5642
FU NIH [P01NS058793, NS042861, NS058793, AT000613, FD003359]
FX Support by the NIH (grants P01NS058793, NS042861, NS058793, AT000613,
and FD003359 to H. D. R. and S. M. H., and NS058793 to G.D.).
NR 24
TC 29
Z9 29
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD MAR 11
PY 2014
VL 82
IS 10
BP 850
EP 857
DI 10.1212/WNL.0000000000000187
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA AH9TJ
UT WOS:000336485100010
PM 24510496
ER
PT J
AU Bramhall, NF
Shi, F
Arnold, K
Hochedlinger, K
Edge, ASB
AF Bramhall, Naomi F.
Shi, Fuxin
Arnold, Katrin
Hochedlinger, Konrad
Edge, Albert S. B.
TI Lgr5-Positive Supporting Cells Generate New Hair Cells in the Postnatal
Cochlea
SO STEM CELL REPORTS
LA English
DT Article
ID EAR SENSORY EPITHELIA; MAMMALIAN INNER-EAR; PROGENITOR CELLS;
REGENERATIVE PROLIFERATION; INTESTINAL CRYPTS; ACOUSTIC TRAUMA;
STEM-CELLS; NOTCH; MOUSE; INHIBITION
AB The prevalence of hearing loss after damage to the mammalian cochlea has been thought to be due to a lack of spontaneous regeneration of hair cells, the primary receptor cells for sound. Here, we show that supporting cells, which surround hair cells in the normal cochlear epithelium, differentiate into new hair cells in the neonatal mouse following ototoxic damage. Using lineage tracing, we show that new hair cells, predominantly outer hair cells, arise from Lgr5-expressing inner pillar and third Deiters cells and that new hair cell generation is increased by pharmacological inhibition of Notch. These data suggest that the neonatal mammalian cochlea has some capacity for hair cell regeneration following damage alone and that Lgr5-positive cells act as hair cell progenitors in the cochlea.
C1 [Bramhall, Naomi F.; Shi, Fuxin; Edge, Albert S. B.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
[Bramhall, Naomi F.; Shi, Fuxin; Edge, Albert S. B.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA.
[Bramhall, Naomi F.; Edge, Albert S. B.] Harvard & MIT, Div Hlth Sci & Technol, Program Speech & Hearing Biosci & Technol, Cambridge, MA 02139 USA.
[Arnold, Katrin; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
RP Edge, ASB (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
EM albert_edge@meei.harvard.edu
FU NIH Ruth L. Kirschstein National Research Service Award; Tillotson
Corporation; Shulsky Foundation; [RO1 DC007174]; [R21 DC010440]; [P30
DC05209]; [R01 DK96034]
FX We thank Drs. M. Charles Liberman, Cynthia Morton, and Matthew Kelley
for helpful comments. This work was supported by grants RO1 DC007174,
R21 DC010440, P30 DC05209, and R01 DK96034; an NIH Ruth L. Kirschstein
National Research Service Award; and the Tillotson Corporation, the
Shulsky Foundation, and Robert Boucai.
NR 42
TC 44
Z9 45
U1 0
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2213-6711
J9 STEM CELL REP
JI Stem Cell Rep.
PD MAR 11
PY 2014
VL 2
IS 3
BP 311
EP 322
DI 10.1016/j.stemcr.2014.01.008
PG 12
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA AI1XE
UT WOS:000336647700007
PM 24672754
ER
PT J
AU Burke, MA
Givertz, MM
AF Burke, Michael A.
Givertz, Michael M.
TI Assessment and Management of Heart Failure After Left Ventricular Assist
Device Implantation
SO CIRCULATION
LA English
DT Article
ID MECHANICAL CIRCULATORY SUPPORT; CONTINUOUS-FLOW; PULMONARY-HYPERTENSION;
INTERNATIONAL SOCIETY; TRANSPLANTATION; THROMBOSIS; NONPULSATILE;
THERAPY
C1 [Burke, Michael A.; Givertz, Michael M.] Harvard Univ, Brigham & Womens Hosp, Cardiovasc Div, Dept Med,Med Sch, Boston, MA 02115 USA.
[Burke, Michael A.] VA Boston Healthcare Syst, Boston, MA USA.
RP Givertz, MM (reprint author), Brigham & Womens Hosp, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA.
EM mgivertz@partners.org
NR 20
TC 5
Z9 6
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 11
PY 2014
VL 129
IS 10
BP 1161
EP U197
DI 10.1161/CIRCULATIONAHA.113.002836
PG 7
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AI2ZH
UT WOS:000336727200018
PM 24615964
ER
PT J
AU Eisendrath, SJ
Gillung, EP
Delucchi, KL
Chartier, M
Mathalon, DH
Sullivan, JC
Segal, ZV
Feldman, MD
AF Eisendrath, Stuart J.
Gillung, Erin P.
Delucchi, Kevin L.
Chartier, Maggie
Mathalon, Daniel H.
Sullivan, Jude C.
Segal, Zindel V.
Feldman, Mitchell D.
TI Mindfulness-based cognitive therapy (MBCT) versus the health-enhancement
program (HEP) for adults with treatment-resistant depression: a
randomized control trial study protocol
SO BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE
LA English
DT Article
DE Depression; Treatment-resistant; Mindfulness; Meditation; MBCT
ID QUALITY-OF-LIFE; COMORBIDITY SURVEY REPLICATION; ILLNESS RATING-SCALE;
MAJOR DEPRESSION; LONGITUDINAL DATA; PRIMARY-CARE; DISORDER; ANXIETY;
OUTPATIENTS; CLINICIAN
AB Background: Major depressive disorder (MDD) is the leading cause of disability in the developed world, yet broadly effective treatments remain elusive. Up to 40% of patients with depression are unresponsive to at least two trials of antidepressant medication and thus have "treatment-resistant depression" (TRD). There is an urgent need for cost-effective, non-pharmacologic, evidence-based treatments for TRD. Mindfulness-Based Cognitive Therapy (MBCT) is an effective treatment for relapse prevention and residual depression in major depression, but has not been previously studied in patients with TRD in a large randomized trial.
Methods/Design: The purpose of this study was to evaluate whether MBCT is an effective augmentation of antidepressants for adults with MDD who failed to respond to standard pharmacotherapy. MBCT was compared to an active control condition, the Health-Enhancement Program (HEP), which incorporates physical activity, functional movement, music therapy and nutritional advice. HEP was designed as a comparator condition for mindfulness-based interventions to control for non-specific effects. Originally investigated in a non-clinical sample to promote stress reduction, HEP was adapted for a depressed population for this study. Individuals age 18 and older with moderate to severe TRD, who failed to respond to at least two trials of antidepressants in the current episode, were recruited to participate. All participants were taking antidepressants (Treatment as usual; TAU) at the time of enrollment. After signing an informed consent, participants were randomly assigned to either MBCT or HEP condition. Participants were followed for 1 year and assessed at weeks 1-7, 8, 24, 36, and 52. Change in depression severity, rate of treatment response and remission after 8 weeks were the primary outcomes measured by the clinician-rated Hamilton Depression Severity Rating (HAM-D) 17-item scale. The participant-rated Quick Inventory of Depression Symptomology (QIDS-SR) 16-item scale was the secondary outcome measure of depression severity, response, and remission.
Discussion: Treatment-resistant depression entails significant morbidity and has few effective treatments. We studied the effect of augmenting antidepressant medication with MBCT, compared with a HEP control, for patients with TRD. Analyses will focus on clinician and patient assessment of depression, participants' clinical global impression change, employment and social functioning scores and quality of life and satisfaction ratings.
C1 [Eisendrath, Stuart J.; Gillung, Erin P.; Delucchi, Kevin L.; Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
[Chartier, Maggie; Mathalon, Daniel H.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
[Sullivan, Jude C.] Univ Wisconsin, Madison Hosp, Madison, WI 53711 USA.
[Sullivan, Jude C.] Univ Wisconsin, Clin Sports Med Ctr, Madison, WI 53711 USA.
[Segal, Zindel V.] Univ Toronto, Dept Psychiat, Toronto, ON M5T 1R8, Canada.
[Feldman, Mitchell D.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA.
RP Eisendrath, SJ (reprint author), Univ Calif San Francisco, Dept Psychiat, 401 Parnassus Ave,Box 0984 AIP, San Francisco, CA 94143 USA.
EM StuartE@lppi.ucsf.edu
RI Segal, Zindel/F-8008-2014
FU NIH/National Center for Complementary and Alternative Medicine (NCCAM)
[R01AT004572]
FX This study is funded by the NIH/National Center for Complementary and
Alternative Medicine (NCCAM) grant number R01AT004572. The authors would
like to gratefully thank Ms. Lauren Erickson, Christa Hogan, Natalie
Holbrook and other members of the research staff who were responsible
for subject recruitment, tracking/scheduling and data collection.
NR 64
TC 12
Z9 12
U1 10
U2 67
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6882
J9 BMC COMPLEM ALTERN M
JI BMC Complement. Altern. Med.
PD MAR 11
PY 2014
VL 14
AR 95
DI 10.1186/1472-6882-14-95
PG 11
WC Integrative & Complementary Medicine
SC Integrative & Complementary Medicine
GA AD8LZ
UT WOS:000333518800002
PM 24612825
ER
PT J
AU Kim, H
Cho, J
Kim, YR
Song, Y
Chun, SI
Suh, JY
Kim, JK
Ryu, YH
Choi, SM
Cho, H
Cho, G
AF Kim, Hyungjun
Cho, Junghun
Kim, Young R.
Song, Youngkyu
Chun, Song-I
Suh, Ji-Yeon
Kim, Jeong Kon
Ryu, Yeon-Hee
Choi, Sun-Mi
Cho, Hyungjoon
Cho, Gyunggoo
TI Response of the Primary Auditory and Non-Auditory Cortices to Acoustic
Stimulation: A Manganese-Enhanced MRI Study
SO PLOS ONE
LA English
DT Article
ID RESONANCE-IMAGING MEMRI; MEDIAL GENICULATE-BODY; VISUAL-CORTEX; INFERIOR
COLLICULUS; FUNCTIONAL-ACTIVITY; SOCIAL STRESS; RAT; PROJECTIONS;
PATHWAY; ORGANIZATION
AB Structural and functional features of various cerebral cortices have been extensively explored in neuroscience research. We used manganese-enhanced MRI, a non-invasive method for examining stimulus-dependent activity in the whole brain, to investigate the activity in the layers of primary cortices and sensory, such as auditory and olfactory, pathways under acoustic stimulation. Male Sprague-Dawley rats, either with or without exposure to auditory stimulation, were scanned before and 24-29 hour after systemic MnCl2 injection. Cortex linearization and layer-dependent signal extraction were subsequently performed for detecting layer-specific cortical activity. We found stimulus-dependent activity in the deep layers of the primary auditory cortex and the auditory pathways. The primary sensory and visual cortices also showed the enhanced activity, whereas the olfactory pathways did not. Further, we performed correlation analysis of the signal intensity ratios among different layers of each cortex, and compared the strength of correlations between with and without the auditory stimulation. In the primary auditory cortex, the correlation strength between left and right hemisphere showed a slight but not significant increase with the acoustic simulation, whereas, in the primary sensory and visual cortex, the correlation coefficients were significantly smaller. These results suggest the possibility that even though the primary auditory, sensory, and visual cortices showed enhanced activity to the auditory stimulation, these cortices had different associations for auditory processing in the brain network.
C1 [Kim, Hyungjun; Song, Youngkyu; Chun, Song-I; Suh, Ji-Yeon; Kim, Jeong Kon; Cho, Gyunggoo] Korea Basic Sci Inst, Div MR, Ochang Eup, Chungbuk, South Korea.
[Kim, Hyungjun; Ryu, Yeon-Hee; Choi, Sun-Mi] Korea Inst Oriental Med, Div Med Res, Taejon, South Korea.
[Cho, Junghun; Cho, Hyungjoon] UNIST, Sch Nanobiosci & Chem Engn, Ulsan, South Korea.
[Kim, Young R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA USA.
[Kim, Jeong Kon] Univ Ulsan, Dept Radiol, Asan Med Ctr, Seoul, South Korea.
RP Cho, H (reprint author), UNIST, Sch Nanobiosci & Chem Engn, Ulsan, South Korea.
EM hjcho@unist.ac.kr; gyunggoo@kbsi.re.kr
RI Cho, HyungJoon/F-1423-2010
FU Korea Basic Science Institute [E33601]; UNIST (Ulsan National Institute
of Science and Technology) [1.130030.01]; Korea Institute of Oriental
Medicine [K13290]
FX This research was supported by grants from the Korea Basic Science
Institute (E33601), from the 2013 Future Challenge Research Fund
(Project No. 1.130030.01) of UNIST (Ulsan National Institute of Science
and Technology), and from the Korea Institute of Oriental Medicine
(K13290). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 38
TC 3
Z9 3
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 11
PY 2014
VL 9
IS 3
AR e90427
DI 10.1371/journal.pone.0090427
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC9GM
UT WOS:000332842400018
PM 24618696
ER
PT J
AU Morris, JC
Tan, AR
Olencki, TE
Shapiro, GI
Dezube, BJ
Reiss, M
Hsu, FJ
Berzofsky, JA
Lawrence, DP
AF Morris, John C.
Tan, Antoinette R.
Olencki, Thomas E.
Shapiro, Geoffrey I.
Dezube, Bruce J.
Reiss, Michael
Hsu, Frank J.
Berzofsky, Jay A.
Lawrence, Donald P.
TI Phase I Study of GC1008 (Fresolimumab): A Human Anti-Transforming Growth
Factor-Beta (TGF beta) Monoclonal Antibody in Patients with Advanced
Malignant Melanoma or Renal Cell Carcinoma
SO PLOS ONE
LA English
DT Article
ID EPITHELIAL-MESENCHYMAL TRANSDIFFERENTIATION; METASTATIC BREAST-CANCER;
SOLID TUMORS; T-CELLS; PROGRESSION; INHIBITION; EFFICACY; SURVIVAL;
VIVO; KERATOACANTHOMAS
AB Background: In advanced cancers, transforming growth factor-beta (TGFb) promotes tumor growth and metastases and suppresses host antitumor immunity. GC1008 is a human anti-TGFb monoclonal antibody that neutralizes all isoforms of TGFb. Here, the safety and activity of GC1008 was evaluated in patients with advanced malignant melanoma and renal cell carcinoma.
Methods: In this multi-center phase I trial, cohorts of patients with previously treated malignant melanoma or renal cell carcinoma received intravenous GC1008 at 0.1, 0.3, 1, 3, 10, or 15 mg/kg on days 0, 28, 42, and 56. Patients achieving at least stable disease were eligible to receive Extended Treatment consisting of 4 doses of GC1008 every 2 weeks for up to 2 additional courses. Pharmacokinetic and exploratory biomarker assessments were performed.
Results: Twenty-nine patients, 28 with malignant melanoma and 1 with renal cell carcinoma, were enrolled and treated, 22 in the dose-escalation part and 7 in a safety cohort expansion. No dose-limiting toxicity was observed, and the maximum dose, 15 mg/kg, was determined to be safe. The development of reversible cutaneous keratoacanthomas/squamous-cell carcinomas (4 patients) and hyperkeratosis was the major adverse event observed. One malignant melanoma patient achieved a partial response, and six had stable disease with a median progression-free survival of 24 weeks for these 7 patients (range, 16.4-44.4 weeks).
Conclusions: GC1008 had no dose-limiting toxicity up to 15 mg/kg. In patients with advanced malignant melanoma and renal cell carcinoma, multiple doses of GC1008 demonstrated acceptable safety and preliminary evidence of antitumor activity, warranting further studies of single agent and combination treatments.
C1 [Morris, John C.; Berzofsky, Jay A.] NCI, Vaccine Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Morris, John C.; Berzofsky, Jay A.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Tan, Antoinette R.; Reiss, Michael] Canc Inst New Jersey, Dept Med, New Brunswick, NJ USA.
[Olencki, Thomas E.] Ohio State Univ, Dept Med, Columbus, OH 43210 USA.
[Shapiro, Geoffrey I.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA.
[Dezube, Bruce J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
[Hsu, Frank J.] Genzyme Corp, Cambridge, MA USA.
[Lawrence, Donald P.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
RP Morris, JC (reprint author), Univ Cincinnati, Dept Med, Div Hematol Oncol, Vontz Ctr Mol Studies, ML0562, Cincinnati, OH 45221 USA.
EM morri2j7@ucmail.uc.edu; berzofsj@mail.nih.gov
FU Genzyme Corporation; Center for Cancer Research, National Cancer
Institute (NCI); Genzyme
FX This work was supported by Genzyme Corporation, and in part by the
Intramural Research Program of the Center for Cancer Research, National
Cancer Institute (NCI). Genzyme provided financial support, the
investigational agent GC1008, and supported study design, data
collection and analysis, the decision to publish, and preparation of the
manuscript.
NR 50
TC 41
Z9 46
U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 11
PY 2014
VL 9
IS 3
AR e90353
DI 10.1371/journal.pone.0090353
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC9GM
UT WOS:000332842400014
PM 24618589
ER
PT J
AU Yoon, JC
Ling, AJY
Isik, M
Lee, DYD
Steinbaugh, MJ
Sack, LM
Boduch, AN
Blackwell, TK
Sinclair, DA
Elledge, SJ
AF Yoon, John C.
Ling, Alvin J. Y.
Isik, Meltem
Lee, Dong-Young Donna
Steinbaugh, Michael J.
Sack, Laura M.
Boduch, Abigail N.
Blackwell, T. Keith
Sinclair, David A.
Elledge, Stephen J.
TI GLTSCR2/PICT1 links mitochondrial stress and Myc signaling
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID RIBOSOMAL-PROTEIN L11; C-MYC; MAMMALIAN-CELLS; EXPRESSION; GENES;
INHIBITION; ACTIVATION; LONGEVITY; APOPTOSIS; PATHWAY
AB Mitochondrial defects underlie a multitude of human diseases. Genetic manipulation of mitochondrial regulatory pathways represents a potential therapeutic approach. We have carried out a high-throughput overexpression screen for genes that affect mitochondrial abundance or activity using flow-cytometry-based enrichment of a cell population expressing a high-complexity, concentration-normalized pool of human ORFs. The screen identified 94 candidate mitochondrial regulators including the nuclear protein GLTSCR2, also known as PICT1. GLTSCR2 enhances mitochondrial function and is required for the maintenance of oxygen consumption, consistent with a pivotal role in the control of cellular respiration. RNAi inactivation of the Caenorhabditis elegans ortholog of GLTSCR2 reduces respiration in worms, indicating functional conservation across species. GLTSCR2 controls cellular proliferation and metabolism via the transcription factor Myc, and is induced by mitochondrial stress, suggesting it may constitute a significant component of the mitochondrial signaling pathway.
C1 [Yoon, John C.; Ling, Alvin J. Y.; Isik, Meltem; Lee, Dong-Young Donna; Steinbaugh, Michael J.; Sack, Laura M.; Boduch, Abigail N.; Blackwell, T. Keith; Sinclair, David A.; Elledge, Stephen J.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Yoon, John C.; Lee, Dong-Young Donna; Sack, Laura M.; Boduch, Abigail N.; Elledge, Stephen J.] Brigham & Womens Hosp, Howard Hughes Med Inst, Div Genet, Boston, MA 02114 USA.
[Yoon, John C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Ling, Alvin J. Y.; Sinclair, David A.] Harvard Univ, Sch Med, Paul F Glenn Labs Biol Mech Aging, Boston, MA 02115 USA.
[Isik, Meltem; Steinbaugh, Michael J.; Blackwell, T. Keith] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA.
RP Elledge, SJ (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
EM jcyoon@partners.org; david_sinclair@hms.harvard.edu;
selledge@genetics.med.harvard.edu
OI Steinbaugh, Michael/0000-0002-2403-2221; Sinclair,
David/0000-0002-9936-436X
FU National Institutes of Health; Paul F. Glenn Foundation; United
Mitochondrial Disease Foundation; Juvenile Diabetes Foundation;
[K08DK081612]; [R01GM094398]
FX We thank the Institute of Chemistry and Cell Biology for assistance with
the mini-RNAi screening. This work was supported by K08DK081612 (to
J.C.Y.), R01GM094398 (to T.K.B.), and National Institutes of Health
research grants (to D.A.S. and S.J.E.). D.A.S. is also supported by the
Paul F. Glenn Foundation, the United Mitochondrial Disease Foundation,
the Juvenile Diabetes Foundation, and a gift from the Schulak family.
S.J.E. is an investigator with the Howard Hughes Medical Institute.
NR 31
TC 6
Z9 6
U1 1
U2 7
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 11
PY 2014
VL 111
IS 10
BP 3781
EP 3786
DI 10.1073/pnas.1400705111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC5MK
UT WOS:000332564800040
PM 24556985
ER
PT J
AU Spring, BQ
Abu-Yousif, AO
Palanisami, A
Rizvi, I
Zheng, X
Mai, ZM
Anbil, S
Sears, RB
Mensah, LB
Goldschmidt, R
Erdem, SS
Oliva, E
Hasan, T
AF Spring, Bryan Q.
Abu-Yousif, Adnan O.
Palanisami, Akilan
Rizvi, Imran
Zheng, Xiang
Mai, Zhiming
Anbil, Sriram
Sears, R. Bryan
Mensah, Lawrence B.
Goldschmidt, Ruth
Erdem, S. Sibel
Oliva, Esther
Hasan, Tayyaba
TI Selective treatment and monitoring of disseminated cancer
micrometastases in vivo using dual-function, activatable
immunoconjugates
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE activatable therapeutic agent; activatable imaging agent; photodynamic
therapy; ovarian cancer; molecular imaging
ID GROWTH-FACTOR RECEPTOR; EPITHELIAL OVARIAN-CANCER; INTRAPERITONEAL
PHOTODYNAMIC THERAPY; PERITONEAL CARCINOMATOSIS; PANCREATIC-CANCER;
MURINE MODEL; EX-VIVO; PHOTOIMMUNOTHERAPY; CELLS; MICROENDOSCOPY
AB Drug-resistant micrometastases that escape standard therapies often go undetected until the emergence of lethal recurrent disease. Here, we show that it is possible to treat microscopic tumors selectively using an activatable immunoconjugate. The immunoconjugate is composed of self-quenching, near-infrared chromophores loaded onto a cancer cell-targeting antibody. Chromophore phototoxicity and fluorescence are activated by lysosomal proteolysis, and light, after cancer cell internalization, enabling tumor-confined photo-cytotoxicity and resolution of individual micrometastases. This unique approach not only introduces a therapeutic strategy to help destroy residual drug-resistant cells but also provides a sensitive imaging method to monitor micrometastatic disease in common sites of recurrence. Using fluorescence microendoscopy to monitor immunoconjugate activation and micrometastatic disease, we demonstrate these concepts of "tumor-targeted, activatable photoimmunotherapy" in a mouse model of peritoneal carcinomatosis. By introducing targeted activation to enhance tumor selectively in complex anatomical sites, this study offers prospects for catching early recurrent micrometastases and for treating occult disease.
C1 [Spring, Bryan Q.; Abu-Yousif, Adnan O.; Palanisami, Akilan; Rizvi, Imran; Zheng, Xiang; Mai, Zhiming; Anbil, Sriram; Sears, R. Bryan; Mensah, Lawrence B.; Goldschmidt, Ruth; Erdem, S. Sibel; Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Spring, Bryan Q.; Abu-Yousif, Adnan O.; Palanisami, Akilan; Rizvi, Imran; Zheng, Xiang; Mai, Zhiming; Anbil, Sriram; Mensah, Lawrence B.; Goldschmidt, Ruth; Erdem, S. Sibel; Hasan, Tayyaba] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Hasan, Tayyaba] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
[Hasan, Tayyaba] Harvard Univ, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Hasan, Tayyaba] MIT, Cambridge, MA 02139 USA.
RP Hasan, T (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
EM thasan@mgh.harvard.edu
FU National Institutes of Health [R01-AR40352, RC1-CA146337, R01-CA160998,
P01-CA084203, F32-CA144210]
FX We thank Drs. Jonathan P. Celli and Conor L. Evans for insightful
discussions; Dr. Jie Zhao, Julie LaGraves, Elena Salomatina, and Peggy
Sherwood for expert technical assistance; and Rina P. Spring for a
critical reading. This work was supported by National Institutes of
Health Grants R01-AR40352, RC1-CA146337, R01-CA160998, and P01-CA084203
(to T.H.) and F32-CA144210 (to B.Q.S.).
NR 56
TC 24
Z9 24
U1 6
U2 46
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 11
PY 2014
VL 111
IS 10
BP E933
EP E942
DI 10.1073/pnas.1319493111
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC5MK
UT WOS:000332564800011
PM 24572574
ER
PT J
AU Connors, EC
Chrastil, ER
Sanchez, J
Merabet, LB
AF Connors, Erin C.
Chrastil, Elizabeth R.
Sanchez, Jaime
Merabet, Lotfi B.
TI Action video game play and transfer of navigation and spatial cognition
skills in adolescents who are blind
SO FRONTIERS IN HUMAN NEUROSCIENCE
LA English
DT Article
DE early blind; adolescent; navigation; spatial cognition; gaming for
learning; serious videogames; virtual environment
ID VIRTUAL-REALITY; PEOPLE; MOBILITY; PERCEPTION; CHILDREN; INDIVIDUALS;
ENVIRONMENT; VISION; SYSTEM; MEMORY
AB For individuals who are blind, navigating independently in an unfamiliar environment represents a considerable challenge. Inspired by the rising popularity of video games, we have developed a novel approach to train navigation and spatial cognition skills in adolescents who are blind. Audio-based Environment Simulator (AbES) is a software application that allows for the virtual exploration of an existing building set in an action video game metaphor. Using this ludic-based approach to learning, we investigated the ability and efficacy of adolescents with early onset blindness to acquire spatial information gained from the exploration of a target virtual indoor environment. Following game play, participants were assessed on their ability to transfer and mentally manipulate acquired spatial information on a set of navigation tasks carried out in the real environment. Success in transfer of navigation skill performance was markedly high suggesting that interacting with AbES leads to the generation of an accurate spatial mental representation. Furthermore, there was a positive correlation between success in game play and navigation task performance. The role of virtual environments and gaming in the development of mental spatial representations is also discussed. We conclude that this game based learning approach can facilitate the transfer of spatial knowledge and further, can be used by individuals who are blind for the purposes of navigation in real-world environments.
C1 [Connors, Erin C.; Merabet, Lotfi B.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Lab Visual Neuroplast, Boston, MA 02114 USA.
[Chrastil, Elizabeth R.] Boston Univ, Ctr Memory & Brain, Dept Psychol & Brain Sci, Boston, MA 02215 USA.
[Sanchez, Jaime] Univ Chile, Ctr Adv Res Educat, Dept Comp Sci, Santiago, Chile.
RP Merabet, LB (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Lab Visual Neuroplast, 243 Charles St, Boston, MA 02114 USA.
EM lotfi_merabet@meei.harvard.edu
OI Chrastil, Elizabeth/0000-0003-2544-0152
FU NIH/NEI ROI [EY019924]; Chilean National Rind of Science and Technology,
Fondecyt [1120330]; Program Center Education PBCT-Conicyt [CIE-05]
FX This work was supported by an NIH/NEI ROI GRANT EY019924 (Lotfi B.
Merabet) and also funded by the Chilean National Rind of Science and
Technology, Fondecyt #1120330 and Project CIE-05 Program Center
Education PBCT-Conicyt (Jaime Sanchez). The authors would like to thank
the research participants, as well as Molly Connors, Rabih Dow, Padma
Rajagopal and the staff of the Carroll Center for the Blind (Newton MA,
USA) for their support in carrying out this research.
NR 44
TC 4
Z9 4
U1 6
U2 47
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5161
J9 FRONT HUM NEUROSCI
JI Front. Hum. Neurosci.
PD MAR 11
PY 2014
VL 8
AR 133
DI 10.3389/fnhum.2014.00133
PG 8
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA AC7DB
UT WOS:000332686300001
PM 24653690
ER
PT J
AU Goodman, SG
Wojdyla, DM
Piccini, JP
White, HD
Paolini, JF
Nessel, CC
Berkowitz, SD
Mahaffey, KW
Patel, MR
Sherwood, MW
Becker, RC
Halperin, JL
Hacke, W
Singer, DE
Hankey, GJ
Breithardt, G
Fox, KAA
Califf, RM
AF Goodman, Shaun G.
Wojdyla, Daniel M.
Piccini, Jonathan P.
White, Harvey D.
Paolini, John F.
Nessel, Christopher C.
Berkowitz, Scott D.
Mahaffey, Kenneth W.
Patel, Manesh R.
Sherwood, Matthew W.
Becker, Richard C.
Halperin, Jonathan L.
Hacke, Werner
Singer, Daniel E.
Hankey, Graeme J.
Breithardt, Gunter
Fox, Keith A. A.
Califf, Robert M.
CA ROCKET AF Investigators
TI Factors Associated With Major Bleeding Events
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE anticoagulants; atrial fibrillation; hemorrhage
ID NONVALVULAR ATRIAL-FIBRILLATION; STROKE PREVENTION; RISK-FACTORS;
WARFARIN; ANTICOAGULATION; TRIAL; RIVAROXABAN; COMPLICATIONS;
HEMORRHAGE; PREDICTION
AB Objectives This study sought to report additional safety results from the ROCKET AF (Rivaroxaban Once-daily oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation).
Background The ROCKET AF trial demonstrated similar risks of stroke/systemic embolism and major/nonmajor clinically relevant bleeding (principal safety endpoint) with rivaroxaban and warfarin.
Methods The risk of the principal safety and component bleeding endpoints with rivaroxaban versus warfarin were compared, and factors associated with major bleeding were examined in a multivariable model.
Results The principal safety endpoint was similar in the rivaroxaban and warfarin groups (14.9 vs. 14.5 events/100 patient-years; hazard ratio: 1.03; 95% confidence interval: 0.96 to 1.11). Major bleeding risk increased with age, but there were no differences between treatments in each age category (<65, 65 to 74, >= 75 years; p(interaction) = 0.59). Compared with those without (n = 13,455), patients with a major bleed (n = 781) were more likely to be older, current/prior smokers, have prior gastrointestinal (GI) bleeding, mild anemia, and a lower calculated creatinine clearance and less likely to be female or have a prior stroke/transient ischemic attack. Increasing age, baseline diastolic blood pressure (DBP) >= 90 mm Hg, history of chronic obstructive pulmonary disease or GI bleeding, prior acetylsalicylic acid use, and anemia were independently associated with major bleeding risk; female sex and DBP <90 mm Hg were associated with a decreased risk.
Conclusions Rivaroxaban and warfarin had similar risk for major/nonmajor clinically relevant bleeding. Age, sex, DBP, prior GI bleeding, prior acetylsalicylic acid use, and anemia were associated with the risk of major bleeding. (An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation: NCT00403767) (C) 2014 by the American College of Cardiology Foundation
C1 [Goodman, Shaun G.] Univ Toronto, St Michaels Hosp, Canadian Heart Res Ctr, Toronto, ON M5B 1W8, Canada.
[Goodman, Shaun G.] Univ Toronto, St Michaels Hosp, Terrence Donnelly Heart Ctr, Div Cardiol, Toronto, ON M5B 1W8, Canada.
[Wojdyla, Daniel M.; Piccini, Jonathan P.; Mahaffey, Kenneth W.; Patel, Manesh R.; Sherwood, Matthew W.; Becker, Richard C.; Califf, Robert M.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
[White, Harvey D.] Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.
[Paolini, John F.; Berkowitz, Scott D.] Bayer HealthCare Pharmaceut, Montville, NJ USA.
[Nessel, Christopher C.] Janssen Res & Dev, Raritan, NJ USA.
[Halperin, Jonathan L.] Mt Sinai Med Ctr, Cardiovasc Inst, New York, NY 10029 USA.
[Hacke, Werner] Heidelberg Univ, Heidelberg, Germany.
[Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA.
[Hankey, Graeme J.] Royal Perth Hosp, Perth, WA 6001, Australia.
[Breithardt, Gunter] Hosp Univ Munster, Munster, Germany.
[Fox, Keith A. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland.
[Fox, Keith A. A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland.
[Califf, Robert M.] Duke Univ, Med Ctr, Duke Translat Med Inst, Durham, NC USA.
RP Goodman, SG (reprint author), Univ Toronto, St Michaels Hosp, 30 Bond St,Room 6-034 Queen, Toronto, ON M5B 1W8, Canada.
EM goodmans@chrc.net
RI Hankey, Graeme /H-4968-2014
OI Hankey, Graeme /0000-0002-6044-7328
FU Johnson & Johnson Pharmaceutical Research and Development; Bayer
HealthCare; Bayer; Johnson Johnson; Boehringer Ingelheim; Bristol-Myers
Squibb; Sanofi-Aventis; Resmed; ARCA Biopharma; BMS/Pfizer; Medtronic,
Inc.; Spectranetics; Forest Laboratories; Eli Lilly; AstraZeneca; Eli
Lilly and Company; GlaxoSmithKline; Merck Co., Inc.; Novartis
Pharmaceuticals Corporation; Pozen; Regado Biosciences; Schering-Plough;
Medicines Company; Daiichi Sankyo; Pfizer; AHRQ; NHBLI; Otsuka
Pharmaceutical Co., Ltd.; Ortho McNeil Janssen; Regado; AG HealthCare;
Biotronik, Inc.; Duke Clinical Research Institute; Boston Scientific;
Ortho-McNeil-Janssen Pharmaceuticals; CSL Behring; CVS Caremark;
theheart.org; Meda Pharma; St. Jude; MSD; 3M
FX The ROCKET AF trial was supported by Johnson & Johnson Pharmaceutical
Research and Development and Bayer HealthCare. The Duke Clinical
Research Institute coordinated the trial, managed the database, and
performed the analyses independently of the sponsors. The Executive
Committee designed the trial, was responsible for overseeing the conduct
of the study, retained the ability to independently analyze and present
the data, made the decision to submit the manuscript for publication,
and takes responsibility for the accuracy and completeness of the data
and all analyses. Dr. Goodman has received consulting fees/honoraria
and/or research grant support from Bayer, Johnson & Johnson, Boehringer
Ingelheim, Bristol-Myers Squibb, Sanofi-Aventis. Dr. Piccini has
received consulting fees/honoraria and/or research grant support from
Johnson & Johnson, GE Healthcare, Resmed, ARCA Biopharma, BMS/Pfizer,
Sanofi-Aventis, Medtronic, Inc., Spectranetics, and Forest Laboratories.
Dr. White has received consulting fees/honoraria and/or research grant
support from Sanofi-Aventis, Eli Lilly, The Medicines Company, National
Institutes of Health, Pfizer, Roche, Johnson& Johnson, Schering-Plough,
Merck & Co., Inc. Sharp and Dohme, AstraZeneca, GlaxoSmithKline, Daiichi
Sankyo, Bristol-Myers Squibb, and Regado. Dr. Paolini was employed by
and has held stock options for Bayer HealthCare. Dr. Nessel is employed
by and owns stock in Johnson & Johnson. Dr. Berkowitz is employed by
Bayer HealthCare. Dr. Mahaffey has received consulting fees/honoraria
and/or research grant support from Johnson & Johnson, AstraZeneca,
Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly and
Company, GlaxoSmithKline, Merck & Co., Inc., Novartis Pharmaceuticals
Corporation, Pozen, Regado Biosciences, Sanofi-Aventis, Schering-Plough,
The Medicines Company, Daiichi Sankyo, and Pfizer. Dr. Patel has
received consulting fees/honoraria and/or research grant support from
Johnson & Johnson, AstraZeneca, AHRQ, NHBLI, Bayer, Otsuka
Pharmaceutical Co., Ltd., and Ortho McNeil Janssen. Dr. Becker has
received consulting fees/honoraria and/or research grant support from
Johnson & Johnson, Regado, Boehringer Ingelheim, AstraZeneca, Daiichi
Sankyo, and Bayer. Dr. Halperin has received consulting fees/honoraria
and/or research grant support from AstraZeneca, Bayer AG HealthCare,
Boehringer Ingelheim, Daiichi Sankyo, Johnson & Johnson, Pfizer,
Sanofi-Aventis, Biotronik, Inc., Duke Clinical Research Institute,
Boston Scientific, and Ortho-McNeil-Janssen Pharmaceuticals. Dr. Hacke
has received consulting fees/honoraria and/or research grant support
from Bayer, Johnson & Johnson, and Boehringer Ingelheim. Dr. Singer has
received consulting fees/honoraria and/or research grant support from
Bayer, Bristol-Myers Squibb, CSL Behring, Johnson & Johnson, Merck &
Co., Inc. Pfizer, Sanofi-Aventis, CVS Caremark, Boehringer Ingelheim,
Daiichi Sankyo, Bristol-Myers Squibb, CSL Behring, and Pfizer. Dr.
Hankey has received consulting fees/honoraria and/or research grant
support from Johnson & Johnson, Bayer, and theheart.org. Dr. Breithardt
has received consulting fees/honoraria and/or research grant support
from Bayer HealthCare, Johnson & Johnson, Meda Pharma, Sanofi-Aventis,
St. Jude, Boehringer Ingelheim, Boston Scientific, Otsuka Pharmaceutical
Co., Ltd., MSD, and 3M. Dr. Fox has received consulting fees/honoraria
and/or research grant support from Bayer, Johnson & Johnson, Eli Lilly
and Company, Sanofi-Aventis, AstraZeneca, and Boehringer Ingelheim. Dr.;
Califf has received consulting fees/honoraria and/or research grant
support from Johnson & Johnson, Bayer, Bristol-Myers Squibb, Boehringer
Ingelheim, and Daiichi Sankyo. Dr. Mahaffey is now affiliated with the
Department of Medicine, Stanford University, Stanford, California. All
other authors have reported that they have no relationships relevant to
the contents of this paper to disclose.
NR 24
TC 63
Z9 63
U1 0
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 11
PY 2014
VL 63
IS 9
BP 891
EP 900
DI 10.1016/j.jacc.2013.11.013
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AC3FE
UT WOS:000332399700007
PM 24315894
ER
PT J
AU Colleoni, M
Gelber, RD
AF Colleoni, Marco
Gelber, Richard D.
TI Time to Initiation of Adjuvant Chemotherapy for Early Breast Cancer and
Outcome: The Earlier, the Better?
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID SURVIVAL; SURGERY; THERAPY; TUMORS
C1 [Colleoni, Marco] European Inst Oncol, Int Breast Canc Study Grp, Milan, Italy.
[Gelber, Richard D.] Dana Farber Canc Inst, Int Breast Canc Study Grp, Boston, MA 02115 USA.
RP Colleoni, M (reprint author), European Inst Oncol, Int Breast Canc Study Grp, Milan, Italy.
NR 20
TC 7
Z9 7
U1 2
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 10
PY 2014
VL 32
IS 8
BP 717
EP +
DI 10.1200/JCO.2013.54.3942
PG 4
WC Oncology
SC Oncology
GA AC4IB
UT WOS:000332483400003
PM 24516011
ER
PT J
AU Wood, ME
Kadlubek, P
Pham, TH
Wollins, DS
Lu, KH
Weitzel, JN
Neuss, MN
Hughes, KS
AF Wood, Marie E.
Kadlubek, Pamela
Pham, Trang H.
Wollins, Dana S.
Lu, Karen H.
Weitzel, Jeffrey N.
Neuss, Michael N.
Hughes, Kevin S.
TI Quality of Cancer Family History and Referral for Genetic Counseling and
Testing Among Oncology Practices: A Pilot Test of Quality Measures As
Part of the American Society of Clinical Oncology Quality Oncology
Practice Initiative
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID PRIMARY-CARE PHYSICIANS; RISK-ASSESSMENT; COLORECTAL-CANCER;
OVARIAN-CANCER; BREAST; SUSCEPTIBILITY; GUIDELINES; MANAGEMENT;
STATEMENT; KNOWLEDGE
AB Purpose Family history of cancer (CFH) is important for identifying individuals to receive genetic counseling/testing (GC/GT). Prior studies have demonstrated low rates of family history documentation and referral for GC/GT.
Methods CFH quality and GC/GT practices for patients with breast (BC) or colon cancer (CRC) were assessed in 271 practices participating in the American Society of Clinical Oncology Quality Oncology Practice Initiative in fall 2011.
Results A total of 212 practices completed measures regarding CFH and GC/GT practices for 10,466 patients; 77.4% of all medical records reviewed documented presence or absence of CFH in first-degree relatives, and 61.5% of medical records documented presence or absence of CFH in second-degree relatives, with significantly higher documentation for patients with BC compared with CRC. Age at diagnosis was documented for all relatives with cancer in 30.7% of medical records (BC, 45.2%; CRC, 35.4%; P .001). Referall for GC/GT occurred in 22.1% of all patients with BC or CRC. Of patients with increased risk for hereditary cancer, 52.2% of patients with BC and 26.4% of those with CRC were referred for GC/GT. When genetic testing was performed, consent was documented 77.7% of the time, and discussion of results was documented 78.8% of the time.
Conclusion We identified low rates of complete CFH documentation and low rates of referral for those with BC or CRC meeting guidelines for referral among US oncologists. Documentation and referral were greater for patients with BC compared with CRC. Education and support regarding the importance of accurate CFH and the benefits of proactive high-risk patient management are clearly needed.
C1 [Wood, Marie E.] Univ Vermont, Burlington, VT 05405 USA.
[Kadlubek, Pamela; Pham, Trang H.; Wollins, Dana S.] Amer Soc Clin Oncol, Alexandria, VA USA.
[Lu, Karen H.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Weitzel, Jeffrey N.] City Hope Natl Med Ctr, Duarte, CA 91010 USA.
[Neuss, Michael N.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Hughes, Kevin S.] Mass Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Boston, MA USA.
RP Wood, ME (reprint author), Univ Vermont, Hem Onc, Given E214,89 Beaumont, Burlington, VT 05405 USA.
EM marie.wood@uvm.edu
OI Hughes, Kevin/0000-0003-4084-6484
FU NCI NIH HHS [P30 CA016672, P50 CA083639]
NR 34
TC 36
Z9 36
U1 0
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 10
PY 2014
VL 32
IS 8
BP 824
EP 829
DI 10.1200/JCO.2013.51.4661
PG 6
WC Oncology
SC Oncology
GA AC4IB
UT WOS:000332483400020
PM 24493722
ER
PT J
AU Nikiforow, S
LaCasce, AS
AF Nikiforow, Sarah
LaCasce, Ann S.
TI Targeting Epstein-Barr Virus-Associated Lymphomas
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID CYTOTOXIC T-CELLS; B-CELL; IN-VIVO; EBV; RESPONSES; DISEASE; ANTIGEN;
CD4(+); TRANSPLANTATION; IDENTIFICATION
C1 [Nikiforow, Sarah; LaCasce, Ann S.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Nikiforow, S (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 32
TC 4
Z9 4
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 10
PY 2014
VL 32
IS 8
BP 830
EP 832
DI 10.1200/JCO.2013.53.2994
PG 3
WC Oncology
SC Oncology
GA AC4IB
UT WOS:000332483400021
PM 24493729
ER
PT J
AU Lu, KH
Wood, ME
Daniels, M
Burke, C
Ford, J
Kauff, ND
Kohlmann, W
Lindor, NM
Mulvey, TM
Robinson, L
Rubinstein, WS
Stoffel, EM
Snyder, C
Syngal, S
Merrill, JK
Wollins, DS
Hughes, KS
AF Lu, Karen H.
Wood, Marie E.
Daniels, Molly
Burke, Cathy
Ford, James
Kauff, Noah D.
Kohlmann, Wendy
Lindor, Noralane M.
Mulvey, Therese M.
Robinson, Linda
Rubinstein, Wendy S.
Stoffel, Elena M.
Snyder, Carrie
Syngal, Sapna
Merrill, Janette K.
Wollins, Dana Swartzberg
Hughes, Kevin S.
TI American Society of Clinical Oncology Expert Statement: Collection and
Use of a Cancer Family History for Oncology Providers
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID LI-FRAUMENI SYNDROME; COLORECTAL-CANCER; RISK-ASSESSMENT;
LYNCH-SYNDROME; POLICY STATEMENT; BREAST-CANCER; GENETIC COUNSELORS;
GERMLINE MUTATIONS; NATIONAL SOCIETY; OVARIAN-CANCER
C1 [Lu, Karen H.; Daniels, Molly; Burke, Cathy] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Robinson, Linda] Simmons Comprehens Canc Ctr, Dallas, TX USA.
[Wood, Marie E.] Univ Vermont, Burlington, VT 05405 USA.
[Ford, James] Stanford Univ, Med Ctr, Stanford, CA 94305 USA.
[Kauff, Noah D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Kohlmann, Wendy] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
[Lindor, Noralane M.] Mayo Clin, Scottsdale, AZ USA.
[Mulvey, Therese M.] Southcoast Ctr Canc Care, Fall River, MA USA.
[Syngal, Sapna] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Hughes, Kevin S.] Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Boston, MA 02114 USA.
[Rubinstein, Wendy S.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Stoffel, Elena M.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Snyder, Carrie] Creighton Univ, Omaha, NE 68178 USA.
[Merrill, Janette K.; Wollins, Dana Swartzberg] Amer Soc Clin Oncol, Alexandria, VA USA.
RP Wood, ME (reprint author), Univ Vermont, Hem Onc, Given E214,89 Beaumont, Burlington, VT 05405 USA.
EM marie.wood@uvm.edu
OI Daniels, Molly/0000-0002-5093-5539; Kauff, Noah/0000-0001-7242-6156;
Hughes, Kevin/0000-0003-4084-6484
FU NCI NIH HHS [P50 CA083639, P30 CA016672]
NR 51
TC 43
Z9 46
U1 1
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 10
PY 2014
VL 32
IS 8
BP 833
EP +
DI 10.1200/JCO.2013.50.9257
PG 9
WC Oncology
SC Oncology
GA AC4IB
UT WOS:000332483400022
PM 24493721
ER
PT J
AU Freidlin, B
Sun, ZX
Gray, R
Korn, EL
AF Freidlin, Boris
Sun, Zhuoxin
Gray, Robert
Korn, Edward L.
TI Reply to S. Goteti et al
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
ID RANDOMIZED CLINICAL-TRIALS; ONCOLOGY
C1 [Freidlin, Boris; Korn, Edward L.] NCI, Bethesda, MD 20892 USA.
[Sun, Zhuoxin; Gray, Robert] Dana Farber Canc Inst, Eastern Cooperat Oncol Grp, Boston, MA 02115 USA.
RP Freidlin, B (reprint author), NCI, Bethesda, MD 20892 USA.
NR 8
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 10
PY 2014
VL 32
IS 8
BP 856
EP 856
DI 10.1200/JCO.2013.53.8934
PG 1
WC Oncology
SC Oncology
GA AC4IB
UT WOS:000332483400029
PM 24493728
ER
PT J
AU Yang, JCH
Sequist, LV
AF Yang, James Chih-Hsin
Sequist, Lecia V.
TI Reply to E. R. Haspinger et al
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
C1 [Yang, James Chih-Hsin] Natl Taiwan Univ Hosp, Taipei, Taiwan.
[Sequist, Lecia V.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Sequist, Lecia V.] Harvard Univ, Sch Med, Boston, MA USA.
RP Yang, JCH (reprint author), Natl Taiwan Univ Hosp, Taipei, Taiwan.
OI Yang, James Chih-Hsin/0000-0002-5586-5138
NR 1
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 10
PY 2014
VL 32
IS 8
BP 863
EP 864
DI 10.1200/JCO.2013.54.1920
PG 2
WC Oncology
SC Oncology
GA AC4IB
UT WOS:000332483400033
PM 24493734
ER
PT J
AU Yang, JCH
Sequist, LV
AF Yang, James Chih-Hsin
Sequist, Lecia V.
TI Reply to F. de Marinis et al
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
C1 [Yang, James Chih-Hsin] Natl Taiwan Univ Hosp, Taipei, Taiwan.
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
RP Yang, JCH (reprint author), Natl Taiwan Univ Hosp, Taipei, Taiwan.
OI Yang, James Chih-Hsin/0000-0002-5586-5138
NR 1
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 10
PY 2014
VL 32
IS 8
BP 865
EP 865
DI 10.1200/JCO.2013.54.1904
PG 1
WC Oncology
SC Oncology
GA AC4IB
UT WOS:000332483400035
PM 24493733
ER
PT J
AU Ciocalteu, A
Saftoiu, A
Cartana, T
Gruionu, LG
Pirici, D
Georgescu, CC
Georgescu, CV
Gheonea, DI
Gruionu, G
AF Ciocalteu, Adriana
Saftoiu, Adrian
Cartana, Tatiana
Gruionu, Lucian Gheorghe
Pirici, Daniel
Georgescu, Corneliu Cristian
Georgescu, Claudia-Valentina
Gheonea, Dan Ionut
Gruionu, Gabriel
TI Evaluation of New Morphometric Parameters of Neoangiogenesis in Human
Colorectal Cancer Using Confocal Laser Endomicroscopy (CLE) and Targeted
Panendothelial Markers
SO PLOS ONE
LA English
DT Article
ID ANTI-ANGIOGENIC THERAPY; IN-VIVO; VASCULATURE; MICROVASCULATURE;
VASCULARIZATION; NORMALIZATION; ARCHITECTURE; TORTUOSITY; TUMORS; MODEL
AB The tumor microcirculation is characterized by an abnormal vascular network with dilated, tortuous and saccular vessels. Therefore, imaging the tumor vasculature and determining its morphometric characteristics represent a critical goal for optimizing the cancer treatment that targets the blood vessels (i.e. antiangiogenesis therapy). The aim of this study was to evaluate new vascular morphometric parameters in colorectal cancer, difficult to achieve through conventional immunohistochemistry, by using the confocal laser endomicroscopy method. Fresh biopsies from tumor and normal tissue were collected during colonoscopy from five patients with T3 colorectal carcinoma without metastasis and were marked with fluorescently labeled anti-CD31 antibodies. A series of optical slices spanning 250 mm inside the tissue were immediately collected for each sample using a confocal laser endomicroscope. All measurements were expressed as the mean +/- standard error. The mean diameter of tumor vessels was significantly larger than the normal vessels (9.46 +/- 0.4 mu m vs. 7.60 +/- 0.3 mu m, p = 0.0166). The vessel density was also significantly higher in the cancer vs. normal tissue samples (5541.05 +/- 262.81 vs. 3755.79 +/- 194.96 vessels/mm(3), p = 0.0006). These results were confirmed by immunohistochemistry. In addition, the tortuosity index and vessel lengths were not significantly different (1.05 +/- 0.016 and 28.30 +/- 3.27 mu m in normal tissue, vs. 1.07 +/- 0.008 and 26.49 +/- 3.18 mu m in tumor tissue respectively, p = 0.5357 and p = 0.7033). The daughter/mother ratio (ratio of the sum of the squares of daughter vessel radii over the square of the mother vessel radius) was 1.15 +/- 0.09 in normal tissue, and 1.21 +/- 0.08 in tumor tissue (p = 0.6531). The confocal laser endomicroscopy is feasible for measuring more vascular parameters from fresh tumor biopsies than conventional immunohistochemistry alone. Provided new contrast agents will be clinically available, future in vivo use of CLE could lead to identification of novel biomarkers based on the morphometric characteristics of tumor vasculature.
C1 [Ciocalteu, Adriana; Saftoiu, Adrian; Cartana, Tatiana; Gruionu, Lucian Gheorghe; Gheonea, Dan Ionut; Gruionu, Gabriel] Univ Med & Pharm Craiova, Res Ctr Gastroenterol & Hepatol, Craiova, Romania.
[Gruionu, Lucian Gheorghe] Univ Craiova, Dept Mech Engn, Craiova, Romania.
[Pirici, Daniel] Univ Med & Pharm Craiova, Dept Histol, Craiova, Romania.
[Georgescu, Corneliu Cristian] Univ Med & Pharm Craiova, Dept Pharmacol, Craiova, Romania.
[Georgescu, Corneliu Cristian] Emergency Cty Hosp, Dept Anesthesiol & Intens Care, Craiova, Romania.
[Georgescu, Claudia-Valentina] Emergency Cty Hosp, Dept Pathol, Craiova, Romania.
[Gruionu, Gabriel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Lab Tumor Biol, Boston, MA USA.
RP Saftoiu, A (reprint author), Univ Med & Pharm Craiova, Res Ctr Gastroenterol & Hepatol, Craiova, Romania.
EM adrian.saftoiu@umfcv.ro
RI Gheonea, Dan Ionut/C-3578-2012; Saftoiu, Adrian/C-2792-2011; Gruionu,
Lucian/F-6121-2011;
OI Gruionu, Lucian/0000-0002-4526-0864; Pirici, Daniel/0000-0002-0196-0949;
Pirici, Daniel/0000-0001-9192-7319
FU National Research Council (CNCS), Romania [PN-II-ID-PCE-2011-3-0664,
PN-II-CT-ERC-2012-1]
FX This work was supported from two research grants funded by the National
Research Council (CNCS), Romania, entitled "Clinical and Biomathematical
Modeling of Vascular Changes Following Anti-Angiogenic Therapy in
Advanced Colorectal Carcinoma," contract number
PN-II-ID-PCE-2011-3-0664, and "Real-time Evaluation of Treatment Effects
in Advanced Colorectal Carcinoma," contract number PN-II-CT-ERC-2012-1.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 30
TC 5
Z9 5
U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 10
PY 2014
VL 9
IS 3
AR e91084
DI 10.1371/journal.pone.0091084
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC9FH
UT WOS:000332839300074
PM 24614504
ER
PT J
AU Chen, LQ
Bourguignon, LYW
AF Chen, Liqun
Bourguignon, Lilly Y. W.
TI Hyaluronan-CD44 interaction promotes c-Jun signaling and miRNA21
expression leading to Bcl-2 expression and chemoresistance in breast
cancer cells
SO MOLECULAR CANCER
LA English
DT Article
ID CYTOSKELETON ACTIVATION; CARCINOMA PROGRESSION; CYCLE PROGRESSION; TUMOR
PROGRESSION; HOMING RECEPTOR; BINDING PROTEIN; GENE-EXPRESSION;
UP-REGULATION; MARKER NANOG; KINASE
AB MicroRNA-21 (miR-21) is associated with the development of solid tumors progression including breast cancer. In this study we investigated matrix hyaluronan (HA)-CD44 (a primary HA receptor) interaction with c-Jun N-Terminal Kinase (JNK)/c-Jun signaling in MDA-MB-468 breast cancer cells [a triple-negative (estrogen receptor-negative/progesterone receptor-negative/HER2-negative) breast cancer cell line]. Our results indicated that HA binding to CD44 promotes c-Jun nuclear translocation and transcriptional activation. Further analyses revealed that miR-21 is regulated by an upstream promoter containing AP1 binding site(s), and chromatin immunoprecipitation (CHIP) assays demonstrated that stimulation of miR-21 expression by HA/CD44 interaction is c-Jun-dependent in these breast cancer cells. This process results in an increase of the anti-apoptosis protein Bcl-2 and upregulation of inhibitors of the apoptosis family of proteins (IAPs) as well as chemoresistance in MDA-MB-468 cells. Treatment with c-Jun specific small interfering RNAs effectively blocks HA-mediated c-Jun signaling and abrogates miR-21 production as well as causes downregulation of survival proteins (Bcl-2 and IAPs) and enhancement of chemosensitivity. In addition, our results demonstrated that anti-miR-21 inhibitor not only downregulates Bcl-2/IAP expression but also increases chemosensitivity in HA-treated breast cancer cells. Together, these findings suggest that the HA/CD44-induced c-Jun signaling plays a pivotal role in miR-21 production leading to survival protein (Bcl-2/IAP) upregulation and chemoresistance in triple negative breast cancer cells such as MDA-MB-468 cell line. This novel HA/CD44-mediated c-Jun signaling pathway and miR-21 production provide a new drug target for the future intervention strategies to treat breast cancer.
C1 [Bourguignon, Lilly Y. W.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA.
Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA.
Endocrine Unit 111N2, San Francisco, CA 94121 USA.
RP Bourguignon, LYW (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA.
EM lilly.bourguignon@ucsf.edu
FU Veterans Affairs (VA) [RR & D-1101 RX000601, BIR & D-5101 BX000628];
United States Public Health [R01 CA66163, P01 CA0052925]; DOD grant
FX We gratefully acknowledge the assistance of Dr. Gerard J. Bourguignon in
the preparation and review of this manuscript. This work was supported
by Veterans Affairs (VA) Merit Review Awards (RR & D-1101 RX000601 and
BIR & D-5101 BX000628), United States Public Health grants (R01 CA66163;
P01 CA0052925) and DOD grant. L.Y.W.B is a VA Senior Research Career
NR 60
TC 27
Z9 29
U1 0
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-4598
J9 MOL CANCER
JI Mol. Cancer
PD MAR 8
PY 2014
VL 13
AR 52
DI 10.1186/1476-4598-13-52
PG 13
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA AF2KY
UT WOS:000334542200002
PM 24606718
ER
PT J
AU Chahil-Graf, R
Madani, N
AF Chahil-Graf, Renu
Madani, Navid
TI Women, culture and the HIV epidemic in MENA
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Editorial Material
C1 [Chahil-Graf, Renu] UNAIDS Middle East & North Africa, Reg Support Team, Cairo, Egypt.
[Madani, Navid] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Global Hlth & Socia, Boston, MA 02115 USA.
RP Madani, N (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,CLSB 1010, Boston, MA 02215 USA.
EM navid_madani@dfci.harvard.edu
NR 10
TC 1
Z9 1
U1 0
U2 6
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD MAR 8
PY 2014
VL 17
AR 19074
DI 10.7448/IAS.17.1.19074
PG 2
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA AC8JM
UT WOS:000332779300001
PM 24629846
ER
PT J
AU Luo, J
Baranov, P
Patel, S
Ouyang, H
Quach, J
Wu, F
Qiu, A
Luo, HR
Hicks, C
Zeng, J
Zhu, J
Lu, J
Sfeir, N
Wen, C
Zhang, MX
Reade, V
Patel, S
Sinden, J
Sun, XD
Shaw, P
Young, M
Zhang, K
AF Luo, Jing
Baranov, Petr
Patel, Sherrina
Ouyang, Hong
Quach, John
Wu, Frances
Qiu, Austin
Luo, Hongrong
Hicks, Caroline
Zeng, Jing
Zhu, Jing
Lu, Jessica
Sfeir, Nicole
Wen, Cindy
Zhang, Meixia
Reade, Victoria
Patel, Sara
Sinden, John
Sun, Xiaodong
Shaw, Peter
Young, Michael
Zhang, Kang
TI Human Retinal Progenitor Cell Transplantation Preserves Vision
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Eye; Neuroprogenitor Cell; Retinal Degeneration; Stem Cells;
Transplantation; Retinal Progenitor Cells
ID VISUAL FUNCTION; STEM-CELLS; RCS RATS; PHOTORECEPTOR DEGENERATION;
MACULAR DEGENERATION; GEOGRAPHIC ATROPHY; ROYAL-COLLEGE; RESTORATION;
RESCUE; MODEL
AB Background: Human retinal progenitor cells (hRPCs) are expandable in vitro and represent a possible therapy for retinal degenerative diseases. Results: In a rat model of retinal degeneration, transplantation of hRPCs preserved photoreceptors and visual function. Conclusion: Subretinal injection of hRPCs rescues photoreceptors without causing adverse effects. Significance: This study provides proof of concept for hRPC transplantation and paves the way for further studies and human trials.
Cell transplantation is a potential therapeutic strategy for retinal degenerative diseases involving the loss of photoreceptors. However, it faces challenges to clinical translation due to safety concerns and a limited supply of cells. Human retinal progenitor cells (hRPCs) from fetal neural retina are expandable in vitro and maintain an undifferentiated state. This study aimed to investigate the therapeutic potential of hRPCs transplanted into a Royal College of Surgeons (RCS) rat model of retinal degeneration. At 12 weeks, optokinetic response showed that hRPC-grafted eyes had significantly superior visual acuity compared with vehicle-treated eyes. Histological evaluation of outer nuclear layer (ONL) characteristics such as ONL thickness, spread distance, and cell count demonstrated a significantly greater preservation of the ONL in hRPC-treated eyes compared with both vehicle-treated and control eyes. The transplanted hRPCs arrested visual decline over time in the RCS rat and rescued retinal morphology, demonstrating their potential as a therapy for retinal diseases. We suggest that the preservation of visual acuity was likely achieved through host photoreceptor rescue. We found that hRPC transplantation into the subretinal space of RCS rats was well tolerated, with no adverse effects such as tumor formation noted at 12 weeks after treatment.
C1 [Luo, Jing; Zhang, Kang] Cent S Univ, Xiangya Hosp 2, Dept Ophthalmol, Changsha 410011, Hunan, Peoples R China.
[Luo, Jing; Zhang, Kang] Cent S Univ, Int Acad Translat Med, Changsha 410011, Hunan, Peoples R China.
[Luo, Jing; Patel, Sherrina; Ouyang, Hong; Quach, John; Wu, Frances; Qiu, Austin; Luo, Hongrong; Zeng, Jing; Zhu, Jing; Lu, Jessica; Sfeir, Nicole; Wen, Cindy; Shaw, Peter; Zhang, Kang] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA.
[Luo, Jing; Patel, Sherrina; Ouyang, Hong; Quach, John; Wu, Frances; Qiu, Austin; Luo, Hongrong; Zeng, Jing; Zhu, Jing; Lu, Jessica; Sfeir, Nicole; Wen, Cindy; Shaw, Peter; Zhang, Kang] Univ Calif San Diego, Shiley Eye Ctr, La Jolla, CA 92093 USA.
[Baranov, Petr; Young, Michael] Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA.
[Qiu, Austin; Luo, Hongrong; Zhu, Jing; Zhang, Meixia; Patel, Sara; Sinden, John; Zhang, Kang] West China Hosp, Mol Med Res Ctr, Chengdu 610041, Sichuan, Peoples R China.
[Hicks, Caroline] ReNeuron Ltd, Guildford GU2 7AF, Surrey, England.
[Zeng, Jing] Guangxi Med Univ, Affiliated Hosp 1, Dept Ophthalmol, Nanning 530021, Guangxi, Peoples R China.
[Reade, Victoria] Da Vinci Consulting, Los Angeles, CA 90069 USA.
[Sun, Xiaodong] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 1, Dept Ophthalmol, Shanghai 200080, Peoples R China.
[Sun, Xiaodong] Shanghai Jiao Tong Univ, Eye Res Inst, Shanghai 200080, Peoples R China.
[Zhang, Kang] Vet Affairs Healthcare Syst, San Diego, CA 92161 USA.
RP Sun, XD (reprint author), Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 1, Dept Ophthalmol, Shanghai 200080, Peoples R China.
EM xdsun@sjtu.edu.cn; kang.zhang@gmail.com
RI luo, hongrong/B-2714-2015
OI luo, hongrong/0000-0001-7994-1193
FU 973 Program [2013CB967504, 2014CB964900]; Natural Science Foundation of
China [81130017, 81276019]; National Institutes of Health Director's
Transformative R01 Program [R01 EY021374]; National Institutes of
Health, NEI [R01 EY018660, P30 EY022589]; King Abdulaziz City for
Science and Technology-University of California San Diego Center of
Excellence in Nanomedicine; Macula Vision Research Foundation; Beckman
Initiative for Macular Research; Macular Society; Burroughs Wellcome
Fund Clinical Scientist Award in Translational Research; ReNeuron Ltd.
FX This work was supported by grants from the 973 Program (2013CB967504 and
2014CB964900), Natural Science Foundation of China (81130017 and
81276019), National Institutes of Health Director's Transformative R01
Program (Grant R01 EY021374), and National Institutes of Health Grants
R01 EY018660 and P30 EY022589 from the NEI. This work was also supported
by a grant from the King Abdulaziz City for Science and
Technology-University of California San Diego Center of Excellence in
Nanomedicine, Macula Vision Research Foundation, Beckman Initiative for
Macular Research, Macular Society, the Burroughs Wellcome Fund Clinical
Scientist Award in Translational Research, and a contract from ReNeuron
Ltd.
NR 35
TC 20
Z9 22
U1 0
U2 10
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 7
PY 2014
VL 289
IS 10
BP 6362
EP 6371
DI 10.1074/jbc.M113.513713
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AC3BG
UT WOS:000332389400005
PM 24407289
ER
PT J
AU Lakshmi, SP
Reddy, AT
Zhang, YZ
Sciurba, FC
Mallampalli, RK
Duncan, SR
Reddy, RC
AF Lakshmi, Sowmya P.
Reddy, Aravind T.
Zhang, Yingze
Sciurba, Frank C.
Mallampalli, Rama K.
Duncan, Steven R.
Reddy, Raju C.
TI Down-regulated Peroxisome Proliferator-activated Receptor gamma (PPAR
gamma) in Lung Epithelial Cells Promotes a PPAR gamma Agonist-reversible
Proinflammatory Phenotype in Chronic Obstructive Pulmonary Disease
(COPD)
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Chromatin Histone Modification; Cigarette Smoke; Glucocorticoid
Receptor; Histone Deacetylase; Inflammation; NF-kappa B (NF-KB);
I-kappa-B Kinase; Human Bronchial Epithelial Cells; Oxidative Stress
ID KAPPA-B; GLUCOCORTICOID-RECEPTOR; OXIDATIVE STRESS; PROTEIN-KINASE;
PHOSPHORYLATION; EXPRESSION; RATS; DEGRADATION; INHIBITION; NITRATION
AB Background: The mechanistic role of peroxisome proliferator-activated receptor (PPAR) in chronic obstructive pulmonary disease (COPD) is poorly understood. Results: COPD and cigarette smoke exposure down-regulated PPAR and produced inflammation that PPAR agonists reversed through multiple pathways. Conclusion: PPAR plays a pivotal role in COPD. Significance: PPAR agonists may be the first effective treatment for COPD.
Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory condition and a leading cause of death, with no available cure. We assessed the actions in pulmonary epithelial cells of peroxisome proliferator-activated receptor (PPAR), a nuclear hormone receptor with anti-inflammatory effects, whose role in COPD is largely unknown. We found that PPAR was down-regulated in lung tissue and epithelial cells of COPD patients, via both reduced expression and phosphorylation-mediated inhibition, whereas pro-inflammatory nuclear factor-B (NF-B) activity was increased. Cigarette smoking is the main risk factor for COPD, and exposing airway epithelial cells to cigarette smoke extract (CSE) likewise down-regulated PPAR and activated NF-B. CSE also down-regulated and post-translationally inhibited the glucocorticoid receptor (GR-) and histone deacetylase 2 (HDAC2), a corepressor important for glucocorticoid action and whose down-regulation is thought to cause glucocorticoid insensitivity in COPD. Treating epithelial cells with synthetic (rosiglitazone) or endogenous (10-nitro-oleic acid) PPAR agonists strongly up-regulated PPAR expression and activity, suppressed CSE-induced production and secretion of inflammatory cytokines, and reversed its activation of NF-B by inhibiting the IB kinase pathway and by promoting direct inhibitory binding of PPAR to NF-B. In contrast, PPAR knockdown via siRNA augmented CSE-induced chemokine release and decreases in HDAC activity, suggesting a potential anti-inflammatory role of endogenous PPAR. The results imply that down-regulation of pulmonary epithelial PPAR by cigarette smoke promotes inflammatory pathways and diminishes glucocorticoid responsiveness, thereby contributing to COPD pathogenesis, and further suggest that PPAR agonists may be useful for COPD treatment.
C1 [Lakshmi, Sowmya P.; Reddy, Aravind T.; Zhang, Yingze; Sciurba, Frank C.; Mallampalli, Rama K.; Duncan, Steven R.; Reddy, Raju C.] Univ Pittsburgh, Dept Med, Div Pulm Allergy & Crit Care Med, Sch Med, Pittsburgh, PA 15213 USA.
[Lakshmi, Sowmya P.; Reddy, Aravind T.; Mallampalli, Rama K.; Reddy, Raju C.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA.
RP Reddy, RC (reprint author), Univ Pittsburgh, Dept Med, Div Pulm Allergy & Crit Care Med, Univ Dr C, Pittsburgh, PA 15240 USA.
EM reddyrc@upmc.edu
FU United States Department of Veterans Affairs; National Institutes of
Health [HL093196]
FX This work was supported by a Merit Review award from the United States
Department of Veterans Affairs and National Institutes of Health Grant
HL093196 (to R. C. R).
NR 33
TC 19
Z9 20
U1 0
U2 8
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 7
PY 2014
VL 289
IS 10
BP 6383
EP 6393
DI 10.1074/jbc.M113.536805
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AC3BG
UT WOS:000332389400007
PM 24368768
ER
PT J
AU Polito, D
Cukras, S
Wang, XZ
Spence, P
Moreau, L
D'Andrea, AD
Kee, Y
AF Polito, David
Cukras, Scott
Wang, Xiaozhe
Spence, Paige
Moreau, Lisa
D'Andrea, Alan D.
Kee, Younghoon
TI The Carboxyl Terminus of FANCE Recruits FANCD2 to the Fanconi Anemia
(FA) E3 Ligase Complex to Promote the FA DNA Repair Pathway
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE DNA Damage; DNA Repair; E3 Ubiquitin Ligase; Protein Degradation;
Protein Dynamics; Protein Folding; Protein Targeting; Protein-protein
Interactions; Ubiquitin
ID CROSS-LINK REPAIR; MONOUBIQUITINATED FANCD2; NUCLEAR ACCUMULATION;
SENSITIZES CELLS; DAMAGE RESPONSE; CORE COMPLEX; S-PHASE; PROTEIN;
INHIBITION; IDENTIFICATION
AB Background: Monoubiquitination of FANCD2 and FANCI is critical in the FA pathway. Results: Specific mutations in FANCE that disrupt FANCD2 binding impair the FA pathway. Conclusion: Inhibition of the FANCE-FANCD2 interaction via FANCE point mutations in the C terminus disrupts the FA pathway. Significance: Recruitment of FANCD2 and FANCI to the FA E3 ligase is a critical step in the FA pathway.
Fanconi anemia (FA) is a genome instability syndrome characterized by bone marrow failure and cellular hypersensitivity to DNA cross-linking agents. In response to DNA damage, the FA pathway is activated through the cooperation of 16 FA proteins. A central player in the pathway is a multisubunit E3 ubiquitin ligase complex or the FA core complex, which monoubiquitinates its substrates FANCD2 and FANCI. FANCE, a subunit of the FA core complex, plays an essential role by promoting the integrity of the complex and by directly recognizing FANCD2. To delineate its role in substrate ubiquitination from the core complex assembly, we analyzed a series of mutations within FANCE. We report that a phenylalanine located at the highly conserved extreme C terminus, referred to as Phe-522, is a critical residue for mediating the monoubiquitination of the FANCD2-FANCI complex. Using the FANCE mutant that specifically disrupts the FANCE-FANCD2 interaction as a tool, we found that the interaction-deficient mutant conferred cellular sensitivity in reconstituted FANCE-deficient cells to a similar degree as FANCE null cells, suggesting the significance of the FANCE-FANCD2 interaction in promoting cisplatin resistance. Intriguingly, ectopic expression of the FANCE C terminus fragment alone in FA normal cells disrupts DNA repair, consolidating the importance of the FANCE-FANCD2 interaction in the DNA cross-link repair.
C1 [Polito, David; Cukras, Scott; Spence, Paige; Kee, Younghoon] Univ S Florida, Coll Arts & Sci, Dept Cell Biol Microbiol & Mol Biol, Tampa, FL 33620 USA.
[Wang, Xiaozhe; D'Andrea, Alan D.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
[Moreau, Lisa] Dana Farber Canc Inst, Cytogenet Core Lab, Boston, MA 02115 USA.
RP Kee, Y (reprint author), Univ S Florida, Coll Arts & Sci, Dept Cell Biol Microbiol & Mol Biol, Tampa, FL 33620 USA.
EM Ykee@usf.edu
FU National Institutes of Health [RO1HL52725]; University of South Florida
departmental startup funds
FX This work was supported, in whole or in part, by National Institutes of
Health Grant RO1HL52725 (to A.D.D.) and University of South Florida
departmental startup funds (to Y.K.).
NR 31
TC 10
Z9 11
U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 7
PY 2014
VL 289
IS 10
BP 7003
EP 7010
DI 10.1074/jbc.M113.533976
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AC3BG
UT WOS:000332389400060
PM 24451376
ER
PT J
AU Chen, Y
Li, J
Dunn, S
Xiong, S
Chen, W
Zhao, YT
Chen, BB
Mallampalli, RK
Zou, CB
AF Chen, Yan
Li, Jin
Dunn, Sarah
Xiong, Sheng
Chen, Wei
Zhao, Yutong
Chen, Bill B.
Mallampalli, Rama K.
Zou, Chunbin
TI Histone Deacetylase 2 (HDAC2) Protein-dependent Deacetylation of
Mortality Factor 4-like 1 (MORF4L1) Protein Enhances Its
Homodimerization
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Epigenetics; Histone Acetylase; Histone Deacetylase; Posttranslational
Modification; Proliferation; Protein Complexes; Protein Structure;
Site-directed Mutagenesis
ID CELL-DIFFERENTIATION; CHROMODOMAIN PROTEIN; MESSENGER-RNA; DNA-REPAIR;
MRG15; COMPLEX; GENE; PROLIFERATION; DOMAIN; DIMERIZATION
AB Background: Histone acetyltransferase MORF4L1 forms a homodimer to perform its epigenetic function, but the molecular mechanisms for its homodimerization are unknown. Results: Histone deacetylase HDAC2 deacetylates MORF4L1 at Lys-148 to enhance MORF4L1 homodimerization. Conclusion: HDAC2-dependent deacetylation of MORF4L1 enhances MORF4L1 homodimerization, which facilitates complex formation to repress cellular proliferation. Significance: The molecular control of MORF4L1 homodimerization may impact fundamental cellular processes such as proliferation.
Histone acetyltransferase mortality factor 4-like 1 (MORF4L1) is a relatively new histone acetyltransferase component that exists as a homodimer to exert its epigenetic function. The mechanism of MORF4L1 self-assembly is unknown. Here we report that Lys-148 deacetylation is indispensable for facilitating MORF4L1 self-assembly into a homodimeric unit. Among a stretch of approximate to 10 amino acids in the NH2 terminus between the chromodomain and MORF4-related gene (MRG) domain within MORF4L1, Lys-148 is normally acetylated. Substitution of Lys-148 with arginine augments MORF4L1 self-assembly. However, acetylation mimics of MORF4L1, including K148L and K148Q, abolished its self-assembly of the histone acetyltransferase component. HDAC2, a deacetylase, interacts with and keeps MORF4L1 in a deacetylation status at Lys(148) that triggers MORF4L1 self-assembly. Knockdown of HDAC2 reduces MORF4L1 self-assembly. HDAC2-dependent deacetylation of MORF4L1 enhances MORF4L1 homodimerization, thus facilitating the functionality of complex formation to repress cell proliferation.
C1 [Chen, Yan; Li, Jin; Dunn, Sarah; Xiong, Sheng; Chen, Wei; Zhao, Yutong; Chen, Bill B.; Mallampalli, Rama K.; Zou, Chunbin] Univ Pittsburgh, Dept Med, Acute Lung Injury Ctr Excellence, Pittsburgh, PA 15213 USA.
[Zhao, Yutong; Chen, Bill B.; Mallampalli, Rama K.] Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA.
[Zhao, Yutong; Chen, Bill B.; Mallampalli, Rama K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA 15240 USA.
[Chen, Yan] Cent S Univ, Xiangya Hosp 2, Dept Resp Med, Changsha 410011, Hunan, Peoples R China.
RP Chen, Y (reprint author), Cent S Univ, Xiangya Hosp 2, Dept Resp Med, Changsha 410011, Hunan, Peoples R China.
EM chenyan99727@163.com; zouc@upmc.edu
FU National Institutes of Health [HL096376, HL097376, HL098174, P01
HL114453]; American Heart Association [12SDG12040330]; United States
Department of Veterans Affairs, Veterans Health Administration, Office
of Research and Development, Biomedical Laboratory Research and
Development; United States Department of Veterans Affairs; Natural
Science Foundation of China [81070039, 81270100]
FX This work was supported, in whole or in part, National Institutes of
Health Grants HL096376, HL097376, HL098174, and P01 HL114453 (to R. K.
M.). This work was also supported by American Heart Association Award
12SDG12040330 (to C. Z.); by the United States Department of Veterans
Affairs, Veterans Health Administration, Office of Research and
Development, Biomedical Laboratory Research and Development; and by a
merit review award from the United States Department of Veterans
Affairs.; Supported by Natural Science Foundation of China Grants
81070039 and 81270100. To whom correspondence may be addressed: Dept. of
Respiratory Medicine, The Second Xiangya Hospital, Central-South
University, Changsha, Hunan 410011, China. E-mail: chenyan99727@163.com.
NR 30
TC 2
Z9 2
U1 1
U2 11
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 7
PY 2014
VL 289
IS 10
BP 7092
EP 7098
DI 10.1074/jbc.M113.527507
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AC3BG
UT WOS:000332389400068
PM 24451372
ER
PT J
AU Borand, L
Madec, Y
Laureillard, D
Chou, M
Marcy, O
Pheng, P
Prak, N
Kim, C
Lak, KK
Hak, C
Dim, B
Nerrienet, E
Fontanet, A
Sok, T
Goldfeld, AE
Blanc, FX
Taburet, AM
AF Borand, Laurence
Madec, Yoann
Laureillard, Didier
Chou, Monidarin
Marcy, Olivier
Pheng, Phearavin
Prak, Narom
Kim, Chindamony
Lak, Khemarin Kim
Hak, Chanroeun
Dim, Bunnet
Nerrienet, Eric
Fontanet, Arnaud
Sok, Thim
Goldfeld, Anne E.
Blanc, Francois-Xavier
Taburet, Anne-Marie
TI Plasma Concentrations, Efficacy and Safety of Efavirenz in HIV-Infected
Adults Treated for Tuberculosis in Cambodia (ANRS 1295-CIPRA KH001
CAMELIA Trial)
SO PLOS ONE
LA English
DT Article
ID TRANSCRIPTASE INHIBITOR EFAVIRENZ; ANTIRETROVIRAL TREATMENT;
PHARMACOKINETIC INTERACTIONS; RANDOMIZED-TRIAL; ADVERSE EVENTS;
RIFAMPICIN; NEVIRAPINE; THERAPY; CYP2B6; POLYMORPHISMS
AB Objective: To assess efavirenz plasma concentrations and their association with treatment efficacy and tolerance of efavirenz 600 mg daily in HIV-tuberculosis co-infected patients.
Methods: HIV-infected adults with CD4+ T cell count <= 200/mm(3) received standard 6-month tuberculosis treatment and antiretroviral therapy including a daily-dose of 600 mg of efavirenz, irrespective of their body weight. Mid-dose blood samples were drawn both on tuberculosis treatment (week +2 and week +6 after antiretroviral therapy initiation, and week 22 of follow-up) and off tuberculosis treatment (week 50 of follow-up). Considered therapeutic range was 1,000 to 4,000 ng/mL. Multivariate analysis was performed to evaluate the association between efavirenz concentration below 1,000 ng/mL and virological failure. Linear regression was used to test the association between efavirenz exposure and CD4+ T cell gain. Severe side effects potentially related to efavirenz were described and their association with efavirenz exposure was tested by multivariate analysis.
Results: Efavirenz plasma concentrations were available in 540 patients. Median [interquartile range] efavirenz concentrations were 2,674 ng/mL [1,690-4,533], 2,667 ng/mL [1,753-4,494] and 2,799 ng/mL [1,804-4,744] at week +2, week +6, week 22, respectively, and 2,766 ng/mL [1,941-3,976] at week 50. Efavirenz concentrations were lower at week 50 (off rifampicin) compared to week 22 (on rifampicin) (p < 0.001). Late attendance to study visit and low hemoglobinemia were the only factors associated with an increased risk of efavirenz concentration below 1,000 ng/mL. Efavirenz concentration below 1,000 ng/mL was not associated with treatment failure. Efavirenz concentration above 4,000 ng/mL was associated with higher risk of central nervous system side effects (p < 0.001) and of hepatotoxicity (p < 0.001).
Conclusion: Body weight and tuberculosis treatment were not associated with low efavirenz concentrations or treatment failure, supporting the 600 mg daily-dose of efavirenz in HIV-tuberculosis co-infected patients. High efavirenz concentrations were related to a higher risk of central nervous system side effects and hepatotoxicity.
C1 [Borand, Laurence; Marcy, Olivier; Pheng, Phearavin] Inst Pasteur Cambodge, Epidemiol & Publ Hlth Unit, Phnom Penh, Cambodia.
[Madec, Yoann; Fontanet, Arnaud] Inst Pasteur, Unite Rech & Expertise Epidemiol Malad Emergentes, Paris, France.
[Laureillard, Didier] ANRS, Ho Chi Minh City, Vietnam.
[Chou, Monidarin] Univ Hlth Sci, Fac Pharm, Phnom Penh, Cambodia.
[Prak, Narom] Khmer Soviet Friendship Hosp, Phnom Penh, Cambodia.
[Kim, Chindamony] Donkeo Prov Hosp, Takeo, Cambodia.
[Kim, Chindamony; Dim, Bunnet] Medecins Sans Frontieres, Phnom Penh, Cambodia.
[Lak, Khemarin Kim] Svay Rieng Prov Hosp, Svay Rieng, Cambodia.
[Lak, Khemarin Kim; Sok, Thim; Goldfeld, Anne E.] Cambodian Hlth Comm, Phnom Penh, Cambodia.
[Hak, Chanroeun] Calmette Hosp, Phnom Penh, Cambodia.
[Dim, Bunnet] Siem Reap Referral Hosp, Siem Reap, Cambodia.
[Nerrienet, Eric] Inst Pasteur Cambodge, HIV Hepatitis Lab, Phnom Penh, Cambodia.
[Fontanet, Arnaud] Conservatoire Natl Arts & Metiers, Paris, France.
[Goldfeld, Anne E.] Harvard Univ, Childrens Hosp, Sch Med, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Blanc, Francois-Xavier] Hop Univ Paris Sud, Hop Bicetre, AP HP, Dept Pneumol, Le Kremlin Bicetre, France.
[Blanc, Francois-Xavier] Univ Nantes, CHU Nantes, DHU2020,Serv Pneumol, UMR INSERM 1087,CNRS UMR 6291,Inst Thorax, F-44035 Nantes, France.
[Taburet, Anne-Marie] Hop Univ Paris Sud, Hop Bicetre, AP HP, Dept Clin Pharm, Le Kremlin Bicetre, France.
RP Taburet, AM (reprint author), Hop Univ Paris Sud, Hop Bicetre, AP HP, Dept Clin Pharm, Le Kremlin Bicetre, France.
EM anne-marie.taburet@bct.aphp.fr
RI Blanc, Francois-Xavier/D-7425-2015
FU French National Agency for Research on AIDS and Viral Hepatitis (ANRS);
U.S. National Institutes of Health Division of AIDS; Merieux Foundation
FX The French National Agency for Research on AIDS and Viral Hepatitis
(ANRS), the U.S. National Institutes of Health Division of AIDS and the
Merieux Foundation have supported this work. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 50
TC 6
Z9 6
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 7
PY 2014
VL 9
IS 3
AR e90350
DI 10.1371/journal.pone.0090350
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC4IY
UT WOS:000332485800020
PM 24608960
ER
PT J
AU Tuggle, KL
Birket, SE
Cui, XX
Hong, J
Warren, J
Reid, L
Chambers, A
Ji, D
Gamber, K
Chu, KK
Tearney, G
Tang, LP
Fortenberry, JA
Du, M
Cadillac, JM
Bedwell, DM
Rowe, SM
Sorscher, EJ
Fanucchi, MV
AF Tuggle, Katherine L.
Birket, Susan E.
Cui, Xiaoxia
Hong, Jeong
Warren, Joe
Reid, Lara
Chambers, Andre
Ji, Diana
Gamber, Kevin
Chu, Kengyeh K.
Tearney, Guillermo
Tang, Li Ping
Fortenberry, James A.
Du, Ming
Cadillac, Joan M.
Bedwell, David M.
Rowe, Steven M.
Sorscher, Eric J.
Fanucchi, Michelle V.
TI Characterization of Defects in Ion Transport and Tissue Development in
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-Knockout Rats
SO PLOS ONE
LA English
DT Article
ID ZINC-FINGER NUCLEASES; SURFACE LIQUID DEPTH; NASAL EPITHELIUM; AIRWAY
EPITHELIA; MOUSE MODELS; CFTR; NA+; CL; GENE; HYPERABSORPTION
AB Animal models for cystic fibrosis (CF) have contributed significantly to our understanding of disease pathogenesis. Here we describe development and characterization of the first cystic fibrosis rat, in which the cystic fibrosis transmembrane conductance regulator gene (CFTR) was knocked out using a pair of zinc finger endonucleases (ZFN). The disrupted Cftr gene carries a 16 base pair deletion in exon 3, resulting in loss of CFTR protein expression. Breeding of heterozygous (CFTR+/-) rats resulted in Mendelian distribution of wild-type, heterozygous, and homozygous (CFTR-/-) pups. Nasal potential difference and transepithelial short circuit current measurements established a robust CF bioelectric phenotype, similar in many respects to that seen in CF patients. Young CFTR-/- rats exhibited histological abnormalities in the ileum and increased intracellular mucus in the proximal nasal septa. By six weeks of age, CFTR-/- males lacked the vas deferens bilaterally. Airway surface liquid and periciliary liquid depth were reduced, and submucosal gland size was abnormal in CFTR-/- animals. Use of ZFN based gene disruption successfully generated a CF animal model that recapitulates many aspects of human disease, and may be useful for modeling other CF genotypes, including CFTR processing defects, premature truncation alleles, and channel gating abnormalities.
C1 [Tuggle, Katherine L.; Birket, Susan E.; Hong, Jeong; Tang, Li Ping; Fortenberry, James A.; Du, Ming; Bedwell, David M.; Rowe, Steven M.; Sorscher, Eric J.; Fanucchi, Michelle V.] Univ Alabama Birmingham, Gregory Fleming James Cyst Fibrosis Res Ctr, Birmingham, AL 35294 USA.
[Tuggle, Katherine L.; Fanucchi, Michelle V.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Environm Hlth Sci, Birmingham, AL 35294 USA.
[Birket, Susan E.; Rowe, Steven M.; Sorscher, Eric J.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[Cui, Xiaoxia; Warren, Joe; Reid, Lara; Chambers, Andre; Ji, Diana; Gamber, Kevin] SAGE Labs Inc, St Louis, MO USA.
[Hong, Jeong] Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol, Birmingham, AL USA.
[Chu, Kengyeh K.; Tearney, Guillermo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA.
[Chu, Kengyeh K.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
[Tearney, Guillermo] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Du, Ming; Cadillac, Joan M.] Univ Alabama Birmingham, Anim Resources Program, Off Vice President Res, Birmingham, AL USA.
[Bedwell, David M.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA.
RP Fanucchi, MV (reprint author), Univ Alabama Birmingham, Gregory Fleming James Cyst Fibrosis Res Ctr, Birmingham, AL 35294 USA.
EM fanucchi@uab.edu
OI Gamber, Kevin/0000-0002-0694-7639
FU CF Foundation [R464-CR07]; NIH [P30 DK072482, R01 HL116213]
FX This work was supported by CF Foundation Grant R464-CR07 (www.cff.org)
and NIH P30 DK072482 (www.nih.gov) to EJS and R01 HL116213 to SMR. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 62
TC 27
Z9 27
U1 1
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 7
PY 2014
VL 9
IS 3
AR e91253
DI 10.1371/journal.pone.0091253
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC4IY
UT WOS:000332485800118
PM 24608905
ER
PT J
AU Lee, MN
Ye, C
Villani, AC
Raj, T
Li, WB
Eisenhaure, TM
Imboywa, SH
Chipendo, PI
Ran, FA
Slowikowski, K
Ward, LD
Raddassi, K
McCabe, C
Lee, MH
Frohlich, IY
Hafler, DA
Kellis, M
Raychaudhuri, S
Zhang, F
Stranger, BE
Benoist, CO
De Jager, PL
Regev, A
Hacohen, N
AF Lee, Mark N.
Ye, Chun
Villani, Alexandra-Chloe
Raj, Towfique
Li, Weibo
Eisenhaure, Thomas M.
Imboywa, Selina H.
Chipendo, Portia I.
Ran, F. Ann
Slowikowski, Kamil
Ward, Lucas D.
Raddassi, Khadir
McCabe, Cristin
Lee, Michelle H.
Frohlich, Irene Y.
Hafler, David A.
Kellis, Manolis
Raychaudhuri, Soumya
Zhang, Feng
Stranger, Barbara E.
Benoist, Christophe O.
De Jager, Philip L.
Regev, Aviv
Hacohen, Nir
TI Common Genetic Variants Modulate Pathogen-Sensing Responses in Human
Dendritic Cells
SO SCIENCE
LA English
DT Article
ID PATTERN-RECOGNITION RECEPTORS; MYCOBACTERIUM-TUBERCULOSIS INFECTION;
GENOME-WIDE ASSOCIATION; TOLL-LIKE RECEPTORS; INNATE IMMUNITY;
EXPRESSION; LOCI; ARCHITECTURE; RESISTANCE; INFLUENZA
AB Little is known about how human genetic variation affects the responses to environmental stimuli in the context of complex diseases. Experimental and computational approaches were applied to determine the effects of genetic variation on the induction of pathogen-responsive genes in human dendritic cells. We identified 121 common genetic variants associated in cis with variation in expression responses to Escherichia coli lipopolysaccharide, influenza, or interferon-beta (IFN-beta). We localized and validated causal variants to binding sites of pathogen-activated STAT ( signal transducer and activator of transcription) and IRF (IFN-regulatory factor) transcription factors. We also identified a common variant in IRF7 that is associated in trans with type I IFN induction in response to influenza infection. Our results reveal common alleles that explain interindividual variation in pathogen sensing and provide functional annotation for genetic variants that alter susceptibility to inflammatory diseases.
C1 [Lee, Mark N.; Ye, Chun; Villani, Alexandra-Chloe; Raj, Towfique; Li, Weibo; Eisenhaure, Thomas M.; Ran, F. Ann; Ward, Lucas D.; McCabe, Cristin; Kellis, Manolis; Raychaudhuri, Soumya; De Jager, Philip L.; Regev, Aviv; Hacohen, Nir] Broad Inst Massachusetts Inst Technol MIT & Harva, Cambridge, MA 02142 USA.
[Lee, Mark N.; Villani, Alexandra-Chloe; Raj, Towfique; Imboywa, Selina H.; Chipendo, Portia I.; Lee, Michelle H.; Frohlich, Irene Y.; Raychaudhuri, Soumya; Benoist, Christophe O.; De Jager, Philip L.; Hacohen, Nir] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Lee, Mark N.; Li, Weibo; Eisenhaure, Thomas M.; Hacohen, Nir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA.
[Raj, Towfique; McCabe, Cristin; De Jager, Philip L.] Brigham & Womens Hosp, Dept Neurol, Program Translat NeuroPsychiat Genom, Boston, MA 02115 USA.
[Ran, F. Ann] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
[Ran, F. Ann] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA.
[Ran, F. Ann; Zhang, Feng] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
[Ran, F. Ann; Hafler, David A.; Zhang, Feng] MIT, Dept Biol Engn, Cambridge, MA 02139 USA.
[Slowikowski, Kamil] Harvard Univ, Grad Sch Arts & Sci, Cambridge, MA 02138 USA.
[Ward, Lucas D.; Kellis, Manolis] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
[Raddassi, Khadir] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06511 USA.
[Raychaudhuri, Soumya] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
[Raychaudhuri, Soumya] Brigham & Womens Hosp, Dept Med, Div Rheumatol, Boston, MA 02115 USA.
[Raychaudhuri, Soumya] Univ Manchester, Manchester Acad Hlth Sci Ctr, Musculoskeletal Res Grp, Arthrit Res UK Epidemiol Unit, Manchester M13 9NT, Lancs, England.
[Stranger, Barbara E.] Univ Chicago, Med Genet Sect, Chicago, IL 60637 USA.
[Stranger, Barbara E.] Univ Chicago, Inst Genom & Syst Biol, Chicago, IL 60637 USA.
[Regev, Aviv] MIT, Dept Biol, Cambridge, MA 02139 USA.
[Regev, Aviv] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Regev, A (reprint author), Broad Inst Massachusetts Inst Technol MIT & Harva, Cambridge, MA 02142 USA.
EM aregev@broad.mit.edu; nhacohen@partners.org
OI Ward, Lucas/0000-0002-8017-809X; Stranger, Barbara/0000-0001-9021-7331
FU National Institute of General Medical Sciences, NIH [RC2 GM093080];
National Institute of Allergy and Infectious Diseases [U19 AI082630];
NIH [DP2 OD002230, DP1 CA174427, R01 HG004037, DP1 MH100706, R01
DK097768, T32 GM007753, F32 AG043267, T32 HG002295]; National Human
Genome Research Institute [P50 HG006193]; Howard Hughes Medical
Institute; Keck Foundation; McKnight Foundation; Merkin Foundation;
Vallee Foundation; Damon Runyon Foundation; Searle Scholars Foundation;
Klingenstein Foundation; Simons Foundation
FX We thank all study participants in the PhenoGenetic project for their
contributions. We are grateful to Q. Sievers and C. Wu for advice about
preparing primary cells and V. Agarwala and D. A. Landau for valuable
discussions. This work was supported by the National Institute of
General Medical Sciences, NIH, grant RC2 GM093080 (C.O.B. and N.H.); the
National Institute of Allergy and Infectious Diseases grant U19 AI082630
and NIH Director's New Innovator Award DP2 OD002230 (N.H.); the National
Human Genome Research Institute grant P50 HG006193, NIH Director's
Pioneer Award DP1 CA174427, and Howard Hughes Medical Institute (A.R.);
and NIH grant R01 HG004037 (M.K.). F.Z. is supported by an NIH
Director's Pioneer Award (DP1 MH100706), an NIH Transformative R01 grant
(R01 DK097768), the Keck, McKnight, Merkin, Vallee, Damon Runyon, Searle
Scholars, Klingenstein, and Simons Foundations, Bob Metcalfe, and Jane
Pauley. M.N.L. is supported by the NIH Medical Scientist Training
Program fellowship (T32 GM007753). T.R. is supported by NIH fellowship
F32 AG043267. K.S. is supported by NIH grant T32 HG002295. Gene
expression data are deposited in National Center for Biotechnology
Information's Gene Expression Omnibus under accession no. GSE53166.
NR 44
TC 111
Z9 111
U1 4
U2 37
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD MAR 7
PY 2014
VL 343
IS 6175
BP 1119
EP +
AR 1246980
DI 10.1126/science.1246980
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC2LB
UT WOS:000332331500042
PM 24604203
ER
PT J
AU Petibon, Y
El Fakhri, G
Nezafat, R
Johnson, N
Brady, T
Ouyang, J
AF Petibon, Y.
El Fakhri, G.
Nezafat, R.
Johnson, N.
Brady, T.
Ouyang, J.
TI Towards coronary plaque imaging using simultaneous PET-MR: a simulation
study
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
DE motion correction; PET-MR; coronary plaque imaging; fat-MR
ID POSITRON-EMISSION-TOMOGRAPHY; ATHEROSCLEROTIC PLAQUE; MOTION
COMPENSATION; LESION DETECTION; RISK-FACTORS; INFLAMMATION; FAT;
RECONSTRUCTION; FEASIBILITY; SEPARATION
AB Coronary atherosclerotic plaque rupture is the main cause of myocardial infarction and the leading killer in the US. Inflammation is a known bio-marker of plaque vulnerability and can be assessed non-invasively using fluorodeoxyglucose-positron emission tomography imaging (FDG-PET). However, cardiac and respiratory motion of the heart makes PET detection of coronary plaque very challenging. Fat surrounding coronary arteries allows the use of MRI to track plaque motion during simultaneous PET-MR examination. In this study, we proposed and assessed the performance of a fat-MR based coronary motion correction technique for improved FDG-PET coronary plaque imaging in simultaneous PET-MR. The proposed methods were evaluated in a realistic four-dimensional PET-MR simulation study obtained by combining patient water-fat separated MRI and XCAT anthropomorphic phantom. Five small lesions were digitally inserted inside the patients coronary vessels to mimic coronary atherosclerotic plaques. The heart of the XCAT phantom was digitally replaced with the patient's heart. Motion-dependent activity distributions, attenuation maps, and fat-MR volumes of the heart, were generated using the XCAT cardiac and respiratory motion fields. A full Monte Carlo simulation using Siemens mMR's geometry was performed for each motion phase. Cardiac/respiratory motion fields were estimated using nonrigid registration of the transformed fat-MR volumes and incorporated directly into the system matrix of PET reconstruction along with motion-dependent attenuation maps. The proposed motion correction method was compared to conventional PET reconstruction techniques such as no motion correction, cardiac gating, and dual cardiac-respiratory gating. Compared to uncorrected reconstructions, fat-MR based motion compensation yielded an average improvement of plaque-to-background contrast of 29.6%, 43.7%, 57.2%, and 70.6% for true plaque-to-blood ratios of 10, 15, 20 and 25: 1, respectively. Channelized Hotelling observer (CHO) signal-to-noise ratio (SNR) was used to quantify plaque detectability. CHO-SNR improvement ranged from 105% to 128% for fat-MR-based motion correction as compared to no motion correction. Likewise, CHO-SNR improvement ranged from 348% to 396% as compared to both cardiac and dual cardiac-respiratory gating approaches. Based on this study, our approach, a fat-MR based motion correction for coronary plaque PET imaging using simultaneous PET-MR, offers great potential for clinical practice. The ultimate performance and limitation of our approach, however, must be fully evaluated in patient studies.
C1 [Petibon, Y.; El Fakhri, G.; Johnson, N.; Brady, T.; Ouyang, J.] Massachusetts Gen Hosp, Dept Imaging, Div Nucl Med & Mol Imaging, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA.
[Petibon, Y.] UPMC Univ Paris 06, Univ Sorbonne, INSERM, Lab Imagerie Biomed,CNRS,UMR S 1146,UMR 7371, F-75013 Paris, France.
[El Fakhri, G.; Nezafat, R.; Brady, T.; Ouyang, J.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Nezafat, R.] Beth Israel Med Deaconess Ctr, Dept Med, Div Cardiovasc, Boston, MA 02215 USA.
RP Ouyang, J (reprint author), Massachusetts Gen Hosp, Dept Imaging, Div Nucl Med & Mol Imaging, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA.
EM ouyang.jinsong@mgh.harvard.edu
FU NIH [R21-EB012326, R01-CA165221, R01-EB008743]
FX This work was supported in part by NIH grants R21-EB012326, R01-CA165221
and R01-EB008743. The authors would like to thank Dr Carmella Nappi for
her help on the locations of the inserted plaques.
NR 42
TC 14
Z9 14
U1 1
U2 9
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
EI 1361-6560
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD MAR 7
PY 2014
VL 59
IS 5
DI 10.1088/0031-9155/59/5/1203
PG 20
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA AB7DR
UT WOS:000331950000008
PM 24556608
ER
PT J
AU Babitt, JL
Lin, HY
AF Babitt, Jodie L.
Lin, Herbert Y.
TI BuMPing iron with modified heparins
SO BLOOD
LA English
DT Editorial Material
ID HEPCIDIN EXPRESSION; INFLAMMATION; METABOLISM; ANEMIA
C1 [Babitt, Jodie L.; Lin, Herbert Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Babitt, JL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
FU NIDDK NIH HHS [R01 DK071837, R01 DK087727]
NR 10
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAR 6
PY 2014
VL 123
IS 10
BP 1440
EP 1441
DI 10.1182/blood-2014-01-549519
PG 4
WC Hematology
SC Hematology
GA AH0XR
UT WOS:000335844600006
PM 24627550
ER
PT J
AU Richardson, PG
Xie, WL
Jagannath, S
Jakubowiak, A
Lonial, S
Raje, NS
Alsina, M
Ghobrial, IM
Schlossman, RL
Munshi, NC
Mazumder, A
Vesole, DH
Kaufman, JL
Colson, K
McKenney, M
Lunde, LE
Feather, J
Maglio, ME
Warren, D
Francis, D
Hideshima, T
Knight, R
Esseltine, DL
Mitsiades, CS
Weller, E
Anderson, KC
AF Richardson, Paul G.
Xie, Wanling
Jagannath, Sundar
Jakubowiak, Andrzej
Lonial, Sagar
Raje, Noopur S.
Alsina, Melissa
Ghobrial, Irene M.
Schlossman, Robert L.
Munshi, Nikhil C.
Mazumder, Amitabha
Vesole, David H.
Kaufman, Jonathan L.
Colson, Kathleen
McKenney, Mary
Lunde, Laura E.
Feather, John
Maglio, Michelle E.
Warren, Diane
Francis, Dixil
Hideshima, Teru
Knight, Robert
Esseltine, Dixie-Lee
Mitsiades, Constantine S.
Weller, Edie
Anderson, Kenneth C.
TI A phase 2 trial of lenalidomide, bortezomib, and dexamethasone in
patients with relapsed and relapsed/refractory myeloma
SO BLOOD
LA English
DT Article
ID DIAGNOSED MULTIPLE-MYELOMA; STEM-CELL TRANSPLANTATION; LOW-DOSE
DEXAMETHASONE; PEGYLATED LIPOSOMAL DOXORUBICIN; THALIDOMIDE PLUS
DEXAMETHASONE; TERM-FOLLOW-UP; PERIPHERAL NEUROPATHY; INDUCTION
TREATMENT; RANDOMIZED PHASE-3; III TRIAL
AB In this prospective, multicenter, phase 2 study, 64 patients with relapsed or relapsed and refractory multiple myeloma (MM) received up to 8 21-day cycles of bortezomib 1.0 mg/m(2) (days 1, 4, 8, and 11), lenalidomide 15 mg/day (days 1-14), and dexamethasone 40/20 mg/day (cycles 1-4) and 20/10 mg/day (cycles 5-8) (days of/after bortezomib dosing). Responding patients could receive maintenance therapy. Median age was 65 years; 66% were male, 58% had relapsed and 42% had relapsed and refractory MM, and 53%, 75%, and 6% had received prior bortezomib, thalidomide, and lenalidomide, respectively. Forty-eight of 64 patients (75%; 90% confidence interval, 65-84) were alive without progressive disease at 6 months (primary end point). The rate of partial response or better was 64%; median duration of response was 8.7 months. Median progression-free and overall survivals were 9.5 and 30 months, respectively (median follow-up: 44 months). Common treatment-related toxicities included sensory neuropathy (53%), fatigue (50%), and neutropenia (42%); common grade 3/4 treatment-related toxicities included neutropenia (30%), thrombocytopenia (22%), and lymphopenia (11%). Grade 3 motor neuropathy was reported in 2 patients. Lenalidomide-bortezomib-dexamethasone appears effective and tolerable in patients with relapsed or relapsed and refractory MM, demonstrating substantial activity among patients with diverse prior therapies and adverse prognostic characteristics. This trial is registered with www.clinicaltrials.gov as #NCT00378209.
C1 [Richardson, Paul G.; Xie, Wanling; Ghobrial, Irene M.; Schlossman, Robert L.; Munshi, Nikhil C.; Colson, Kathleen; McKenney, Mary; Lunde, Laura E.; Feather, John; Maglio, Michelle E.; Warren, Diane; Hideshima, Teru; Mitsiades, Constantine S.; Weller, Edie; Anderson, Kenneth C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Jagannath, Sundar] Mt Sinai Med Ctr, Tisch Canc Inst, New York, NY 10029 USA.
[Jakubowiak, Andrzej] Univ Michigan, Ctr Comprehens Canc, Div Hematol Oncol, Ann Arbor, MI 48109 USA.
[Lonial, Sagar; Kaufman, Jonathan L.; Francis, Dixil] Emory Univ, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA.
[Raje, Noopur S.] Massachusetts Gen Hosp, Ctr Multiple Myeloma, Boston, MA 02114 USA.
[Alsina, Melissa] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Blood & Marrow Transplantat, Tampa, FL 33682 USA.
[Mazumder, Amitabha] NYU, Dept Med, Ctr Comprehens Canc, New York, NY 10016 USA.
[Vesole, David H.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Multiple Myeloma Div, Hackensack, NJ USA.
[Knight, Robert] Celgene Inc, Oncol Res & Dev, Summit, NJ USA.
[Esseltine, Dixie-Lee] Millennium, Oncol Clin Res, Cambridge, MA USA.
RP Richardson, PG (reprint author), Dana Farber Canc Inst, 44 Binney St,Dana 1B02, Boston, MA 02115 USA.
EM paul_richardson@dfci.harvard.edu
FU The Rick Corman Multiple Myeloma Research Fund; Millennium: The Takeda
Oncology Company; Celgene Corporation
FX This work was supported by The Rick Corman Multiple Myeloma Research
Fund, Millennium: The Takeda Oncology Company, and the Celgene
Corporation.
NR 51
TC 63
Z9 65
U1 0
U2 6
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAR 6
PY 2014
VL 123
IS 10
BP 1461
EP 1469
DI 10.1182/blood-2013-07-517276
PG 9
WC Hematology
SC Hematology
GA AH0XR
UT WOS:000335844600012
PM 24429336
ER
PT J
AU Bitan, M
He, WS
Zhang, MJ
Abdel-Azim, H
Ayas, MF
Bielorai, B
Carpenter, PA
Cairo, MS
Diaz, MA
Horan, JT
Jodele, S
Kitko, CL
Schultz, KR
Kletzel, M
Kasow, KA
Lehmann, LE
Mehta, PA
Shah, N
Pulsipher, MA
Prestidge, T
Seber, A
Shenoy, S
Woolfrey, AE
Yu, LC
Davies, SM
AF Bitan, Menachem
He, Wensheng
Zhang, Mei-Jie
Abdel-Azim, Hisham
Ayas, Mouhab Fakhreddine
Bielorai, Bella
Carpenter, Paul A.
Cairo, Mitchell S.
Angel Diaz, Miguel
Horan, John T.
Jodele, Sonata
Kitko, Carrie L.
Schultz, Kirk R.
Kletzel, Morris
Kasow, Kimberly A.
Lehmann, Leslie E.
Mehta, Parinda A.
Shah, Nirali
Pulsipher, Michael A.
Prestidge, Tim
Seber, Adriana
Shenoy, Shalini
Woolfrey, Ann E.
Yu, Lolie C.
Davies, Stella M.
TI Transplantation for children with acute myeloid leukemia: a comparison
of outcomes with reduced intensity and myeloablative regimens
SO BLOOD
LA English
DT Article
ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; ALLOGENEIC
TRANSPLANTATION; CURRENT CONTROVERSIES; SURVIVAL; DISEASE; THERAPY;
FAILURE; RECEIVE; VIEW
AB The safety and efficacy of reduced-intensity conditioning (RIC) regimens for the treatment of pediatric acute myeloid leukemia is unknown. We compared the outcome of allogeneic hematopoietic cell transplantation in children with acute myeloid leukemia using RIC regimens with those receiving myeloablative-conditioning (MAC) regimens. A total of 180 patients were evaluated (39 with RIC and 141 with MAC regimens). Results of univariate and multivariate analysis showed no significant differences in the rates of acute and chronic graft-versus-host disease, leukemia-free, and overall survival between treatment groups. The 5-year probabilities of overall survival with RIC and MAC regimens were 45% and 48%, respectively (P = .99). Moreover, relapse rates were not higher with RIC compared with MAC regimens (39% vs 39%; P = .95), and recipients of MAC regimens were not at higher risk for transplant-related mortality compared with recipients of RIC regimens (16% vs 16%; P = .73). After carefully controlled analyses, we found that in this relatively modest study population, the data supported a role for RIC regimens for acute myeloid leukemia in children undergoing allogeneic hematopoietic cell transplantation. The data also provided justification for designing a carefully controlled randomized clinical trial that examines the efficacy of regimen intensity in this population.
C1 [Bitan, Menachem] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Pediat Hematol Oncol, IL-69978 Tel Aviv, Israel.
[He, Wensheng] Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Zhang, Mei-Jie] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA.
[Zhang, Mei-Jie] Childrens Hosp Los Angeles, Div Hematol Oncol & Blood Marrow Transplant Res I, Los Angeles, CA USA.
[Abdel-Azim, Hisham] Univ So Calif, Dept Pediat, Keck Sch Med, Los Angeles, CA 90089 USA.
[Ayas, Mouhab Fakhreddine] King Faisal Specialist Hosp & Res Ctr, Dept Pediat Hematol Oncol, Riyadh 11211, Saudi Arabia.
[Bielorai, Bella] Chaim Sheba Med Ctr, Dept Pediat Hematol Oncol & BMT, IL-52621 Tel Hashomer, Israel.
[Carpenter, Paul A.; Woolfrey, Ann E.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Cairo, Mitchell S.] New York Med Coll, Dept Pediat, Valhalla, NY 10595 USA.
[Angel Diaz, Miguel] Hosp Nino Jesus, Unidad Trasplante Hematopoyet, Madrid, Spain.
[Horan, John T.] Childrens Healthcare Atlanta Egleston, Atlanta, GA USA.
[Jodele, Sonata; Mehta, Parinda A.; Davies, Stella M.] Cincinnati Childrens Hosp Med Ctr, Div Bone Marrow Transplantat & Immune Deficiency, Cincinnati, OH 45229 USA.
[Kitko, Carrie L.] Univ Michigan, Pediat & Communicable Dis Blood & Marrow Transpla, Ann Arbor, MI 48109 USA.
[Schultz, Kirk R.] British Columbia Childrens Hosp, Vancouver, BC, Canada.
[Kletzel, Morris] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL USA.
[Kasow, Kimberly A.] Univ North Carolina Hosp, Div Pediat Hematol Oncol, Chapel Hill, NC USA.
[Lehmann, Leslie E.] Dana Farber Canc Inst, Pediat Stem Cell Transplant Unit, Boston, MA 02115 USA.
[Shah, Nirali] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Pulsipher, Michael A.] Univ Utah, Primary Childrens Med Ctr, Div Hematol Hematol Malignancies, Huntsman Canc Inst, Salt Lake City, UT USA.
[Prestidge, Tim] Starship Childrens Hosp, Auckland, New Zealand.
[Seber, Adriana] Inst Oncol Pediat, Sao Paulo, Brazil.
[Shenoy, Shalini] Washington Univ, St Louis Childrens Hosp, Pediat Stem Cell Transplant Program, St Louis, MO 63110 USA.
[Yu, Lolie C.] Louisiana State Univ, Div Hematol Oncol, Childrens Hosp, New Orleans, LA USA.
RP Davies, SM (reprint author), Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave,MLC 11027, Cincinnati, OH 45229 USA.
EM stella.davies@cchmc.org
FU Public Health Service grant from the National Cancer Institute
[U24-CA76518]; National Heart Lung and Blood Institute; National
Institute of Allergy and Infectious Diseases; Health Resources and
Services Administration [HHSH234200637051C]
FX This study was funded by Public Health Service grant (U24-CA76518) from
the National Cancer Institute, the National Heart Lung and Blood
Institute, the National Institute of Allergy and Infectious Diseases,
and the Health Resources and Services Administration
(HHSH234200637051C).
NR 24
TC 16
Z9 17
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAR 6
PY 2014
VL 123
IS 10
BP 1615
EP 1620
DI 10.1182/blood-2013-10-535716
PG 6
WC Hematology
SC Hematology
GA AH0XR
UT WOS:000335844600030
PM 24435046
ER
PT J
AU Ecker, JL
AF Ecker, Jeffrey L.
TI NEW ENGLAND JOURNAL of MEDICINE
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
AB The case of Marlise Munoz, in which a Texas hospital was made to withdraw support from a pregnant woman who had been brain dead for 2 months, should underscore women's right to determine the course of their end-of-life care, whether or not they are pregnant. Marlise Munoz was 33 years old and the mother of a 15-month-old when she collapsed on November 26, 2013, from what was later determined to be a massive pulmonary embolism. Initially described as apneic but alive, she was brought to the county hospital where her family was soon told that she was brain dead. Ms. Munoz and her husband, both emergency medical technicians (EMTs), had discussed their feelings about such situations. So Erik Munoz felt confident in asserting that his wife would not want continued support. Her other family members agreed, and they requested withdrawal of ventilation and other measures ...
C1 [Ecker, Jeffrey L.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA.
[Ecker, Jeffrey L.] Harvard Univ, Sch Med, Boston, MA USA.
RP Ecker, JL (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA.
NR 2
TC 4
Z9 4
U1 1
U2 10
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAR 6
PY 2014
VL 370
IS 10
BP 889
EP 891
DI 10.1056/NEJMp1400969
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA AC2EB
UT WOS:000332309800003
PM 24499176
ER
PT J
AU Lieber, DS
Hershman, SG
Slate, NG
Calvo, SE
Sims, KB
Schmahmann, JD
Mootha, VK
AF Lieber, Daniel S.
Hershman, Steven G.
Slate, Nancy G.
Calvo, Sarah E.
Sims, Katherine B.
Schmahmann, Jeremy D.
Mootha, Vamsi K.
TI Next generation sequencing with copy number variant detection expands
the phenotypic spectrum of HSD17B4-deficiency
SO BMC MEDICAL GENETICS
LA English
DT Article
DE HSD17B4; DBP; D-bifunctional protein deficiency; Perrault syndrome;
Next-generation sequencing; Exome sequencing; Copy number variants; CNV;
Mitochondria; Mitochondrial disorders; Mitochondrial disease; Mendelian
disorders; Human genetics; Ataxia; Multi-system disorders; Peroxisomal
defects
ID BIFUNCTIONAL PROTEIN-DEFICIENCY; CAUSE OVARIAN DYSGENESIS; PERRAULT
SYNDROME; BETA-OXIDATION; HEARING-LOSS; MUTATIONS; TYPE-4; MICE
AB Background: D-bifunctional protein deficiency, caused by recessive mutations in HSD17B4, is a severe, infantile-onset disorder of peroxisomal fatty acid oxidation. Few affected patients survive past two years of age. Compound heterozygous mutations in HSD17B4 have also been reported in two sisters diagnosed with Perrault syndrome (MIM # 233400), who presented in adolescence with ovarian dysgenesis, hearing loss, and ataxia.
Case presentation: An adult male presented with cerebellar ataxia, peripheral neuropathy, hearing loss, and azoospermia. The clinical presentation, in combination with biochemical findings in serum, urine, and muscle biopsy, suggested a mitochondrial disorder. Commercial genetic testing of 18 ataxia and mitochondrial disease genes was negative. Targeted exome sequencing followed by analysis of single nucleotide variants and small insertions/deletions failed to reveal a genetic basis of disease. Application of a computational algorithm to infer copy number variants (CNVs) from exome data revealed a heterozygous 12 kb deletion of exons 10-13 of HSD17B4 that was compounded with a rare missense variant (p.A196V) at a highly conserved residue. Retrospective review of patient records revealed mildly elevated ratios of pristanic: phytanic acid and arachidonic: docosahexaenoic acid, consistent with dysfunctional peroxisomal fatty acid oxidation.
Conclusion: Our case expands the phenotypic spectrum of HSD17B4-deficiency, representing the first male case reported with infertility. Furthermore, it points to crosstalk between mitochondria and peroxisomes in HSD17B4-deficiency and Perrault syndrome.
C1 [Lieber, Daniel S.; Hershman, Steven G.; Slate, Nancy G.; Calvo, Sarah E.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA.
[Lieber, Daniel S.; Hershman, Steven G.; Slate, Nancy G.; Calvo, Sarah E.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Lieber, Daniel S.; Hershman, Steven G.; Slate, Nancy G.; Calvo, Sarah E.; Sims, Katherine B.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Lieber, Daniel S.; Hershman, Steven G.; Calvo, Sarah E.; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
[Lieber, Daniel S.; Hershman, Steven G.; Calvo, Sarah E.; Mootha, Vamsi K.] Broad Inst Harvard & MIT, Cambridge, MA 02141 USA.
[Sims, Katherine B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Sims, Katherine B.; Schmahmann, Jeremy D.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Schmahmann, Jeremy D.] Massachusetts Gen Hosp, Dept Neurol, Lab Neuroanat & Cerebellar Neurobiol, Cognit Behav Neurol Unit,Ataxia Unit, Boston, MA 02114 USA.
[Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
RP Schmahmann, JD (reprint author), Massachusetts Gen Hosp, Dept Neurol, Lab Neuroanat & Cerebellar Neurobiol, Cognit Behav Neurol Unit,Ataxia Unit, Boston, MA 02114 USA.
EM jschmahmann@partners.org; vamsi@hms.harvard.edu
OI Hershman, Steven/0000-0001-9167-7380
FU NSF Graduate Research Fellowship; DOD National Defense Science and
Engineering Graduate Fellowship; NGHRI/NIH [RC2HG005556, R01GM97136];
Marriott Mitochondrial Disorders Clinical Research Fund; Birmingham and
MINDlink Foundations
FX We thank S. Vafai, D. McGuone, M. Frosch for discussion and J. Macmore
for research assistance. This work was supported by NSF Graduate
Research Fellowship (DSL), DOD National Defense Science and Engineering
Graduate Fellowship (SGH), grant RC2HG005556 and R01GM97136 from the
NGHRI/NIH (VKM), the Marriott Mitochondrial Disorders Clinical Research
Fund (VKM), and the Birmingham and MINDlink Foundations (JDS).
NR 25
TC 14
Z9 14
U1 1
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2350
J9 BMC MED GENET
JI BMC Med. Genet.
PD MAR 6
PY 2014
VL 15
AR 30
DI 10.1186/1471-2350-15-30
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA AF2IT
UT WOS:000334536500001
PM 24602372
ER
PT J
AU Sun, ZYJ
Cheng, YX
Kim, M
Song, LK
Choi, J
Kudahl, UJ
Brusic, V
Chowdhury, B
Yu, L
Seaman, MS
Bellot, G
Shih, WM
Wagner, G
Reinherz, EL
AF Sun, Zhen-Yu J.
Cheng, Yuxing
Kim, Mikyung
Song, Likai
Choi, Jaewon
Kudahl, Ulrich J.
Brusic, Vladimir
Chowdhury, Barnali
Yu, Lu
Seaman, Michael S.
Bellot, Gaetan
Shih, William M.
Wagner, Gerhard
Reinherz, Ellis L.
TI Disruption of Helix-Capping Residues 671 and 674 Reveals a Role in HIV-1
Entry for a Specialized Hinge Segment of the Membrane Proximal External
Region of gp41
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE viral membrane fusion; NMR solution structure; helix-hinge-helix motif;
helix capping; broadly neutralizing antibody
ID VIRUS TYPE-1 GP41; T-CELL-RECEPTOR; NEUTRALIZING ANTIBODY; ENVELOPE
GLYCOPROTEIN; DIPOLAR COUPLINGS; ATOMIC-STRUCTURE; VIRAL MEMBRANE;
FUSION; PROTEINS; EPITOPE
AB HIV-1 (human immunodeficiency virus type /) uses its trimeric gp160 envelope (Env) protein consisting of non-covalently associated gp120 and gp41 subunits to mediate entry into human T lymphocytes. A facile virus fusion mechanism compensates for the sparse Env copy number observed on viral particles and includes a 22-amino-acid, lentivirus-specific adaptation at the gp41 base (amino acid residues 662-683), termed the membrane proximal external region (MPER). We show by NMR and EPR that the MPER consists of a structurally conserved pair of viral lipid-immersed helices separated by a hinge with tandem joints that can be locked by capping residues between helices. This design fosters efficient HIV-1 fusion via interconverting structures while, at the same time, affording immune escape. Disruption of both joints by double alanine mutations at Env positions 671 and 674 (AA) results in attenuation of Env-mediated cell cell fusion and hemifusion, as well as viral infectivity mediated by both CD4-dependent and CD4-independent viruses. The potential mechanism of disruption was revealed by structural analysis of MPER conformational changes induced by AA mutation. A deeper acyl chain-buried MPER middle section and the elimination of cross-hinge rigid-body motion almost certainly impede requisite structural rearrangements during the fusion process, explaining the absence of MPER AA variants among all known naturally occurring HIV-1 viral sequences. Furthermore, those broadly neutralization antibodies directed against the HIV-1 MPER exploit the tandem joint architecture involving helix capping, thereby disrupting hinge function. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Sun, Zhen-Yu J.; Bellot, Gaetan; Shih, William M.; Wagner, Gerhard] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Cheng, Yuxing; Kim, Mikyung; Choi, Jaewon; Reinherz, Ellis L.] Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA.
[Cheng, Yuxing; Kim, Mikyung; Choi, Jaewon; Kudahl, Ulrich J.; Brusic, Vladimir; Reinherz, Ellis L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Kim, Mikyung; Brusic, Vladimir; Reinherz, Ellis L.] Harvard Univ, Dept Med, Sch Med, Boston, MA 02115 USA.
[Song, Likai; Chowdhury, Barnali; Yu, Lu] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32310 USA.
[Kudahl, Ulrich J.; Brusic, Vladimir] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA.
[Seaman, Michael S.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA.
[Bellot, Gaetan; Shih, William M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Bellot, Gaetan; Shih, William M.] Wyss Inst Biol Inspired Engn Harvard, Boston, MA 02115 USA.
RP Reinherz, EL (reprint author), Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA.
EM Ellis_Reinherz@dfci.harvard.edu
FU National Institutes of Health [A1084785, A1091693, GM047467,
1DP20D004641, 1U54GM094608]; Biological Sciences in Public Health at
Harvard School of Public Health, Boston, MA, USA; National High Magnetic
Field Laboratory User Collaboration Grants Program [5080]; National
Science Foundation [DMR1157490]; Department of Energy and the State of
Florida
FX This work is funded by National Institutes of Health Grants A1084785 and
A1091693 to E.L.R., GM047467 to G.W. and 1DP20D004641 and 1U54GM094608
to W.S., as well as Gates Foundation Grants to E.L.R. and M.S.S. Y.C. is
affiliated with the PhD Program in Biological Sciences in Public Health
at Harvard School of Public Health, Boston, MA, USA. L.S. acknowledges
the support of National High Magnetic Field Laboratory User
Collaboration Grants Program Grant No. 5080. The National High Magnetic
Field Laboratory is funded by National Science Foundation Cooperative
Agreement No. DMR1157490, Department of Energy and the State of Florida.
We thank Drs. J. G. Sodroski, B. Haynes, R. Swanstrom and R. T. Wyatt
for reagents; Drs. J. Chou and M. Allan for advice with RDC data; J. -H.
Wang for comments; and G. Heffron for assistance with NMR instruments.
NR 42
TC 12
Z9 14
U1 0
U2 11
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
EI 1089-8638
J9 J MOL BIOL
JI J. Mol. Biol.
PD MAR 6
PY 2014
VL 426
IS 5
SI SI
BP 1095
EP 1108
DI 10.1016/j.jmb.2013.09.030
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AD0FG
UT WOS:000332909300009
PM 24075869
ER
PT J
AU Cardo, LF
Coto, E
de Mena, L
Ribacoba, R
Mata, IF
Menendez, M
Moris, G
Alvarez, V
AF Cardo, Lucia F.
Coto, Eliecer
de Mena, Lorena
Ribacoba, Rene
Mata, Ignacio F.
Menendez, Manuel
Moris, German
Alvarez, Victoria
TI Alpha-synuclein transcript isoforms in three different brain regions
from Parkinson's disease and healthy subjects in relation to the SNCA
rs356165/rs11931074 polymorphisms
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE Parkinson's disease; Alpha-synuclein isoforms; DNA polymorphisms;
Genetic risk
ID MESSENGER-RNA EXPRESSION; GENE; SUSCEPTIBILITY; VARIANTS
AB Mutations in the alpha-synuclein (SNCA) gene cause autosomal dominant Parkinson's disease (PD). Common SNCA polymorphisms have been associated with the risk of developing PD. Abnormal expression and post-translational modification of SNCA has been found in PD-brains. In addition to a full length transcript (SNCA-140) there are three short isoforms (SNCA-98, -112, and -126) that could be prone to aggregation. The association between SNCA polymorphisms and PD could be explained through an increased expression of these alternative transcripts. Our aim was to measure the different SNCA transcripts in the substantia nigra (SN), cerebellum (CB), and occipital cortex (OC) from PD-patients (n = 9) and healthy subjects (n = 6). In addition, we determined whether two SNCA polymorphisms (SNPs rs356165 and rs11931074) were related to differences in transcript isoform expression. PD brain tissues showed higher levels of the three short transcripts in the SN, but only SNCA-112 and SNCA-98 were significantly increased in the CB of patients vs. controls (p = 0.02, p = 0.03). The genotyping of a large cohort of PD-patients and controls showed that haplotype rs356165-A+rs11931074-G had a protective effect (OR = 0.71; CI = 0.59-0.83), while the G-T haplotype increased the risk for PD (OR = 1.44; CI = 1.06-1.96). We did not find significant differences for the SNCA levels between the haplotypes. In conclusion, we found statistically significant higher levels of the SNCA-112 and SNCA-98 transcripts in the CB of PD brains, and a trend toward higher levels of the short transcript isoforms in the SN of PD brains. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
C1 [Cardo, Lucia F.; Coto, Eliecer; de Mena, Lorena; Alvarez, Victoria] Hosp Univ Cent Asturias, Genet Mol Lab Med, Oviedo, Spain.
[Ribacoba, Rene; Menendez, Manuel; Moris, German] Hosp Univ Cent Asturias, Asturias, Spain.
[Ribacoba, Rene; Menendez, Manuel; Moris, German] Alvarez Buylla Mieres, Asturias, Spain.
[Mata, Ignacio F.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA.
[Mata, Ignacio F.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA.
RP Alvarez, V (reprint author), Hosp Cent Asturias Maternidad, Oviedo 33006, Spain.
EM victoria.alvarez@sespa.princast.es
FU Spanish "Fondo de Investigaciones Sanitarias-Fondos FEDER" European
Union [FIS 11/0093]; FICYT-Principado de Asturias; Fundacion Parkinson
Asturias; Obra Social Cajastur
FX We thank Dr. Claire Troakes and the London Neurodegenerative Diseases
Brain Bank for supplying all postmortem brain samples. Authors thank the
"Fundacion Parkinson Asturias" and "Obra Social Cajastur" for their
support. This work was supported by grants from the Spanish "Fondo de
Investigaciones Sanitarias-Fondos FEDER" European Union (FIS 11/0093).
LFC and LDM are predoctoral fellowships of FICYT-Principado de Asturias.
NR 20
TC 10
Z9 10
U1 0
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3940
EI 1872-7972
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD MAR 6
PY 2014
VL 562
BP 45
EP 49
DI 10.1016/j.neulet.2014.01.009
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA AD0FM
UT WOS:000332909900009
PM 24418406
ER
PT J
AU Spires-Jones, TL
Friedman, T
Pitstick, R
Polydoro, M
Roe, A
Carlson, GA
Hyman, BT
AF Spires-Jones, Tara L.
Friedman, Taylor
Pitstick, Rose
Polydoro, Manuela
Roe, Allyson
Carlson, George A.
Hyman, Bradley T.
TI Methylene blue does not reverse existing neurofibrillary tangle
pathology in the rTg4510 mouse model of tauopathy
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE Alzheimer; Tau; Methylene blue
ID EARLY ALZHEIMERS-DISEASE; TAU; NEUROPROTECTION; PHENOTHIAZINES;
INHIBITION
AB Alzheimer's disease is characterized pathologically by aggregation of amyloid beta into senile plaques and aggregation of pathologically modified tau into neurofibrillary tangles. While changes in amyloid processing are strongly implicated in disease initiation, the recent failure of amyloid-based therapies has highlighted the importance of tau as a therapeutic target. "Tangle busting" compounds including methylene blue and analogous molecules are currently being evaluated as therapeutics in Alzheimer's disease. Previous studies indicated that methylene blue can reverse tau aggregation in vitro after 10 min, and subsequent studies suggested that high levels of drug reduce tau protein levels (assessed biochemically) in vivo. Here, we tested whether methylene blue could remove established neurofibrillary tangles in the rTg4510 model of tauopathy, which develops robust tangle pathology. We find that 6 weeks of methylene blue dosing in the water from 16 months to 17.5 months of age decreases soluble tau but does not remove sarkosyl insoluble tau, or histologically defined PHF1 or Gallyas positive tangle pathology. These data indicate that methylene blue treatment will likely not rapidly reverse existing tangle pathology. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
C1 [Spires-Jones, Tara L.; Friedman, Taylor; Polydoro, Manuela; Roe, Allyson; Hyman, Bradley T.] Massachusetts Gen Hosp, Charlestown, MA 02129 USA.
[Pitstick, Rose; Carlson, George A.] McLaughlin Res Inst, Great Falls, MT USA.
RP Spires-Jones, TL (reprint author), Univ Edinburgh, Ctr Cognit & Neural Syst, 1 George Sq, Edinburgh EH9 3EL, Midlothian, Scotland.
EM tara.spires-jones@ed.ac.uk
OI Spires-Jones, Tara/0000-0003-2530-0598
FU NIA NIH HHS [R00 AG033670, R01 AG026249, P50 AG005134]
NR 18
TC 19
Z9 19
U1 0
U2 9
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3940
EI 1872-7972
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD MAR 6
PY 2014
VL 562
BP 63
EP 68
DI 10.1016/j.neulet.2014.01.013
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA AD0FM
UT WOS:000332909900013
PM 24462887
ER
PT J
AU Tragante, V
Barnes, MR
Ganesh, SK
Lanktree, MB
Guo, W
Franceschini, N
Smith, EN
Johnson, T
Holmes, MV
Padmanabhan, S
Karczewski, KJ
Almoguera, B
Barnard, J
Baumert, J
Chang, YPC
Elbers, CC
Farrall, M
Fischer, ME
Gaunt, TR
Gho, JMIH
Gieger, C
Goel, A
Gong, Y
Isaacs, A
Kleber, ME
Leach, IM
McDonough, CW
Meijs, MFL
Melander, O
Nelson, CP
Nolte, IM
Pankratz, N
Price, TS
Shaffer, J
Shah, S
Tomaszewski, M
van der Most, PJ
Van Iperen, EPA
Vonk, JM
Witkowska, K
Wong, COL
Zhang, L
Beitelshees, AL
Berenson, GS
Bhatt, DL
Brown, M
Burt, A
Cooper-DeHoff, RM
Connell, JM
Cruickshanks, KJ
Curtis, SP
Davey-Smith, G
Delles, C
Gansevoort, RT
Guo, XQ
Haiqing, S
Hastie, CE
Hofker, MH
Hovingh, GK
Kim, DS
Kirkland, SA
Klein, BE
Klein, R
Li, YR
Maiwald, S
Newton-Cheh, C
O'Brien, ET
Onland-Moret, NC
Palmas, W
Parsa, A
Penninx, BW
Pettinger, M
Vasan, RS
Ranchalis, JE
Ridker, PM
Rose, LM
Sever, P
Shimbo, D
Steele, L
Stolk, RP
Thorand, B
Trip, MD
van Duijn, CM
Verschuren, WM
Wijmenga, C
Wyatt, S
Young, JH
Zwinderman, AH
Bezzina, CR
Boerwinkle, E
Casas, JP
Caulfield, MJ
Chakravarti, A
Chasman, DI
Davidson, KW
Doevendans, PA
Dominiczak, AF
FitzGerald, GA
Gums, JG
Fornage, M
Hakonarson, H
Halder, I
Hillege, HL
Illig, T
Jarvik, GP
Johnson, JA
Kastelein, JJP
Koenig, W
Kumari, M
Marz, W
Murray, SS
O'Connell, JR
Oldehinkel, AJ
Pankow, JS
Rader, DJ
Redline, S
Reilly, MP
Schadt, EE
Kottke-Marchant, K
Snieder, H
Snyder, M
Stanton, AV
Tobin, MD
Uitterlinden, AG
van der Harst, P
van der Schouw, YT
Samani, NJ
Watkins, H
Johnson, AD
Reiner, AP
Zhu, XF
de Bakker, PIW
Levy, D
Asselbergs, FW
Munroe, PB
Keating, BJ
AF Tragante, Vinicius
Barnes, Michael R.
Ganesh, Santhi K.
Lanktree, Matthew B.
Guo, Wei
Franceschini, Nora
Smith, Erin N.
Johnson, Toby
Holmes, Michael V.
Padmanabhan, Sandosh
Karczewski, Konrad J.
Almoguera, Berta
Barnard, John
Baumert, Jens
Chang, Yen-Pei Christy
Elbers, Clara C.
Farrall, Martin
Fischer, Mary E.
Gaunt, Tom R.
Gho, Johannes M. I. H.
Gieger, Christian
Goel, Anuj
Gong, Yan
Isaacs, Aaron
Kleber, Marcus E.
Leach, Irene Mateo
McDonough, Caitrin W.
Meijs, Matthijs F. L.
Melander, Olle
Nelson, Christopher P.
Nolte, Ilja M.
Pankratz, Nathan
Price, Tom S.
Shaffer, Jonathan
Shah, Sonia
Tomaszewski, Maciej
van der Most, Peter J.
Van Iperen, Erik P. A.
Vonk, Judith M.
Witkowska, Kate
Wong, Caroline O. L.
Zhang, Li
Beitelshees, Amber L.
Berenson, Gerald S.
Bhatt, Deepak L.
Brown, Morris
Burt, Amber
Cooper-DeHoff, Rhonda M.
Connell, John M.
Cruickshanks, Karen J.
Curtis, Sean P.
Davey-Smith, George
Delles, Christian
Gansevoort, Ron T.
Guo, Xiuqing
Haiqing, Shen
Hastie, Claire E.
Hofker, Marten H.
Hovingh, G. Kees
Kim, Daniel S.
Kirkland, Susan A.
Klein, Barbara E.
Klein, Ronald
Li, Yun R.
Maiwald, Steffi
Newton-Cheh, Christopher
O'Brien, Eoin T.
Onland-Moret, N. Charlotte
Palmas, Walter
Parsa, Afshin
Penninx, Brenda W.
Pettinger, Mary
Vasan, Ramachandran S.
Ranchalis, Jane E.
Ridker, Paul M.
Rose, Lynda M.
Sever, Peter
Shimbo, Daichi
Steele, Laura
Stolk, Ronald P.
Thorand, Barbara
Trip, Mieke D.
van Duijn, Cornelia M.
Verschuren, W. Monique
Wijmenga, Cisca
Wyatt, Sharon
Young, J. Hunter
Zwinderman, Aeilko H.
Bezzina, Connie R.
Boerwinkle, Eric
Casas, Juan P.
Caulfield, Mark J.
Chakravarti, Aravinda
Chasman, Daniel I.
Davidson, Karina W.
Doevendans, Pieter A.
Dominiczak, Anna F.
FitzGerald, Garret A.
Gums, John G.
Fornage, Myriam
Hakonarson, Hakon
Halder, Indrani
Hillege, Hans L.
Illig, Thomas
Jarvik, Gail P.
Johnson, Julie A.
Kastelein, John J. P.
Koenig, Wolfgang
Kumari, Meena
Maerz, Winfried
Murray, Sarah S.
O'Connell, Jeffery R.
Oldehinkel, Albertine J.
Pankow, James S.
Rader, Daniel J.
Redline, Susan
Reilly, Muredach P.
Schadt, Eric E.
Kottke-Marchant, Kandice
Snieder, Harold
Snyder, Michael
Stanton, Alice V.
Tobin, Martin D.
Uitterlinden, Andre G.
van der Harst, Pim
van der Schouw, Yvonne T.
Samani, Nilesh J.
Watkins, Hugh
Johnson, Andrew D.
Reiner, Alex P.
Zhu, Xiaofeng
de Bakker, Paul I. W.
Levy, Daniel
Asselbergs, Folkert W.
Munroe, Patricia B.
Keating, Brendan J.
TI Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry
Identifies Multiple Blood-Pressure-Related Loci
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; HUMAN PREFRONTAL
CORTEX; FACTOR-KAPPA-B; ESSENTIAL-HYPERTENSION; SUSCEPTIBILITY LOCUS;
CANDIDATE GENES; COMMON VARIANTS; DRUG DISCOVERY; PULSE PRESSURE
AB Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped similar to 50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 x 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.
C1 [Tragante, Vinicius; Gho, Johannes M. I. H.; Meijs, Matthijs F. L.; Doevendans, Pieter A.; Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, NL-3584 CX Utrecht, Netherlands.
[Tragante, Vinicius; Elbers, Clara C.; de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Med Genet, NL-3584 CX Utrecht, Netherlands.
[Barnes, Michael R.] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, Inst Hlth Biomed Res Unit, London EC1M 6BQ, England.
[Ganesh, Santhi K.] Univ Michigan Hlth Syst, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.
[Ganesh, Santhi K.] Univ Michigan Hlth Syst, Dept Human Genet, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.
[Lanktree, Matthew B.] McMaster Univ, Dept Med, Hamilton, ON L8S 4L8, Canada.
[Guo, Wei; Zhu, Xiaofeng] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
[Franceschini, Nora] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Smith, Erin N.] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA.
[Smith, Erin N.] Univ Calif San Diego, Radys Childrens Hosp, La Jolla, CA 92093 USA.
[Johnson, Toby; Witkowska, Kate; Wong, Caroline O. L.; Caulfield, Mark J.; Munroe, Patricia B.] Queen Mary Univ London, London EC1M 6BQ, England.
[Johnson, Toby; Witkowska, Kate; Wong, Caroline O. L.; Caulfield, Mark J.; Munroe, Patricia B.] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Barts & London Genome Ctr, London EC1M 6BQ, England.
[Holmes, Michael V.; Steele, Laura; Keating, Brendan J.] Univ Penn, Dept Surg, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Padmanabhan, Sandosh; Dominiczak, Anna F.] Univ Glasgow, BHF, Glasgow Cardiovasc Res Ctr, Glasgow G12 8TA, Lanark, Scotland.
[Karczewski, Konrad J.; Snyder, Michael] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA.
[Almoguera, Berta; Li, Yun R.; Keating, Brendan J.] Childrens Hosp Philadelphia, Abramson Res Ctr, Ctr Appl Genom, Philadelphia, PA 19104 USA.
[Barnard, John; Zhang, Li] Cleveland Clin, Lerner Res Inst, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA.
[Baumert, Jens; Thorand, Barbara] Helmholtz Zentrum Mu nchen, German Res Ctr Environm Hlth, Inst Epidemiol2, D-85764 Neuherberg, Germany.
[Chang, Yen-Pei Christy] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Chang, Yen-Pei Christy] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Elbers, Clara C.; Hofker, Marten H.; Onland-Moret, N. Charlotte; van der Schouw, Yvonne T.; de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, NL-3584 CX Utrecht, Netherlands.
[Farrall, Martin; Goel, Anuj; Watkins, Hugh] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
[Farrall, Martin; Goel, Anuj; Watkins, Hugh] Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford OX3 9DU, England.
[Fischer, Mary E.; Cruickshanks, Karen J.; Klein, Barbara E.; Klein, Ronald] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI 53726 USA.
[Gaunt, Tom R.; Davey-Smith, George] Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England.
[Gieger, Christian] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, D-85764 Neuherberg, Germany.
[Gong, Yan; McDonough, Caitrin W.; Cooper-DeHoff, Rhonda M.; Johnson, Julie A.] Univ Florida, Dept Pharmacotherapy & Translat Res, Gainesville, FL 32610 USA.
[Gong, Yan; McDonough, Caitrin W.; Cooper-DeHoff, Rhonda M.; Johnson, Julie A.] Univ Florida, Ctr Pharmacogenom, Gainesville, FL 32610 USA.
[Isaacs, Aaron; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, NL-3015 GE Rotterdam, Netherlands.
[Kleber, Marcus E.; Jarvik, Gail P.; Maerz, Winfried] Heidelberg Univ, Med Fac Mannheim, Med Clin 5, D-68167 Mannheim, Germany.
[Leach, Irene Mateo; van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 RB Groningen, Netherlands.
[Melander, Olle] Lund Univ, Dept Clin Sci, S-20502 Malmo, Sweden.
[Melander, Olle] Skane Univ Hosp, Ctr Emergency Med, S-20502 Malmo, Sweden.
[Nelson, Christopher P.; Tomaszewski, Maciej; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.
[Nelson, Christopher P.; Samani, Nilesh J.] Glenfield Hosp, NIHR, Lecister Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England.
[Nolte, Ilja M.; van der Most, Peter J.; Vonk, Judith M.; Snieder, Harold] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9700 RB Groningen, Netherlands.
[Pankratz, Nathan] Univ Minnesota, Dept Lab Med & Pathol, Inst Human Genet, Minneapolis, MN 55455 USA.
[Price, Tom S.] Inst Psychiat, MRC, SGDP Ctr, London SE5 8AF, England.
[Shaffer, Jonathan; Shimbo, Daichi] Columbia Univ, Dept Med, New York, NY 10032 USA.
[Shah, Sonia] UCL, Genet Inst, Dept Genet Evolut & Environm, London WC1E 6BT, England.
[Van Iperen, Erik P. A.; van der Harst, Pim; Asselbergs, Folkert W.] ICIN, Durrer Ctr Cardiogenet Res, Netherlands Heart Inst, NL-3511 GC Utrecht, Netherlands.
[Van Iperen, Erik P. A.; Zwinderman, Aeilko H.] Univ Amsterdam, Acad Med Ctr, Dept Clin Epidemiol Biostat & Bioinformat, NL-1105 AZ Amsterdam, Netherlands.
[Beitelshees, Amber L.; Haiqing, Shen; Parsa, Afshin] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Berenson, Gerald S.] Tulane Univ, Dept Epidemiol, New Orleans, LA 70118 USA.
[Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Brown, Morris] Univ Cambridge, Addenbrookes Hosp, Clin Pharmacol Unit, Cambridge CB2 2QQ, England.
[Burt, Amber; Ranchalis, Jane E.] Univ Washington, Dept Med Med Genet, Seattle, WA 98195 USA.
[Connell, John M.] Univ Dundee, Ninewells Hosp & Med Sch, Dundee DD1 9SY, Scotland.
[Cruickshanks, Karen J.] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53726 USA.
[Curtis, Sean P.] Merck Res Labs, Rahway, NJ 07065 USA.
[Delles, Christian; Hastie, Claire E.] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow G12 8TA, Lanark, Scotland.
[Gansevoort, Ron T.] Univ Groningen, Univ Med Ctr Groningen, Dept Med, Div Nephrol, NL-9700 RB Groningen, Netherlands.
[Guo, Xiuqing] Cedars Sinai Med Ctr, PEDS, Los Angeles, CA 90048 USA.
[Hofker, Marten H.] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, Med Biol Div, NL-9700 RB Groningen, Netherlands.
[Hovingh, G. Kees; Maiwald, Steffi; Kastelein, John J. P.] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands.
[Kim, Daniel S.] Univ Washington, Dept Med Med Genet, Seattle, WA 98195 USA.
[Kim, Daniel S.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Kirkland, Susan A.] Dalhousie Univ, Dept Community Hlth & Epidemiol, Halifax, NS B3H 1V7, Canada.
[Newton-Cheh, Christopher] Massachusetts Gen Hosp, Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
[O'Brien, Eoin T.] Univ Coll Dublin, Conway Inst Biomol & Biomed Res, Dublin 4, Ireland.
[Penninx, Brenda W.] Vrije Univ Amsterdam, Med Ctr, EMGO Inst, Dept Psychiat, NL-1081 BT Amsterdam, Netherlands.
[Pettinger, Mary] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Ridker, Paul M.; Rose, Lynda M.; Chasman, Daniel I.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Ridker, Paul M.; Chasman, Daniel I.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Sever, Peter] Univ London Imperial Coll Sci Technol & Med, Int Ctr Circulatory Hlth, London W2 1LA, England.
[Trip, Mieke D.] Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands.
[Verschuren, W. Monique] Natl Inst Publ Hlth & Environm, RIVM, NL-3720 BA Bilthoven, Netherlands.
[Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands.
[Wyatt, Sharon] Univ Mississippi, Med Ctr, Sch Nursing, Jackson, MS 39216 USA.
[Wyatt, Sharon] Univ Mississippi, Med Ctr, Sch Med, Jackson, MS 39216 USA.
[Young, J. Hunter] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Bezzina, Connie R.] Univ Amsterdam, Acad Med Ctr, Heart Failure Res Ctr, Dept Clin & Expt Cardiol, NL-1105 AZ Amsterdam, Netherlands.
[Bezzina, Connie R.] Univ Amsterdam, Acad Med Ctr, Mol & Expt Cardiol Grp, NL-1105 AZ Amsterdam, Netherlands.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol, Houston, TX 77030 USA.
[Casas, Juan P.] London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, London WC1E 7HT, England.
[Casas, Juan P.] UCL, Dept Epidemiol & Publ Hlth, Genet Epidemiol Grp, London WC1E 6BT, England.
[Chakravarti, Aravinda] Johns Hopkins Univ, Sch Med, Ctr Complex Dis Genom, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
[Davidson, Karina W.] Columbia Univ, Dept Med, New York, NY 10032 USA.
[Davidson, Karina W.] Columbia Univ, Dept Psychiat, New York, NY 10032 USA.
[FitzGerald, Garret A.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA.
[Gums, John G.] Univ Florida, Dept Pharmacotherapy & Translat Res, Gainesville, FL 32610 USA.
[Gums, John G.] Univ Florida, Dept Community Hlth, Gainesville, FL 32610 USA.
[Gums, John G.] Univ Florida, Dept Family Med, Gainesville, FL 32610 USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA.
[Halder, Indrani] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15261 USA.
[Illig, Thomas] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany.
[Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, D-30625 Hannover, Germany.
[Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, D-89081 Ulm, Germany.
[Kumari, Meena] UCL, Dept Epidemiol & Publ Hlth, Div Populat Hlth, London WC1E 7HB, England.
[Jarvik, Gail P.] Synlab Serv GmbH, Synlab Acad, D-69214 Mannheim, Germany.
[Maerz, Winfried] Med Univ Graz, Inst Clin Med, A-8036 Graz, Austria.
[Maerz, Winfried] Med Univ Graz, Chem Lab Diagnost, A-8036 Graz, Austria.
[Murray, Sarah S.] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92037 USA.
[Oldehinkel, Albertine J.] Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, NL-9700 RB Groningen, Netherlands.
[Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA.
[Rader, Daniel J.; Reilly, Muredach P.] Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Redline, Susan] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Schadt, Eric E.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA.
[Kottke-Marchant, Kandice] Cleveland Clin, Pathol & Lab Med Inst, Cleveland, OH 44195 USA.
[Stanton, Alice V.] Royal Coll Surgeons Ireland, Dublin 2, Ireland.
[Tobin, Martin D.] Univ Leicester, Dept Hlth Sci, Leicester LE1 7RH, Leics, England.
[Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.
[Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.
[Johnson, Andrew D.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[de Bakker, Paul I. W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA.
[de Bakker, Paul I. W.] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Levy, Daniel] NHLBI, Ctr Populat Studies, Framingham, MA 01702 USA.
[Asselbergs, Folkert W.] UCL, Fac Populat Hlth Sci, Inst Cardiovasc Sci, London WC1E 6BT, England.
[Keating, Brendan J.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP Munroe, PB (reprint author), Queen Mary Univ London, London EC1M 6BQ, England.
EM p.b.munroe@qmul.ac.uk; bkeating@mail.med.upenn.edu
RI Davey Smith, George/A-7407-2013; Johnson, Andrew/G-6520-2013;
Padmanabhan, Sandosh/S-3963-2016; Wijmenga, Cisca/D-2173-2009; van der
Schouw, Yvonne/F-8327-2014; Shah, Sonia/N-7547-2013; Price,
Thomas/B-7372-2008; Stanton, Alice/F-4697-2012; Jarvik,
Gail/N-6476-2014; Gaunt, Tom/O-3918-2014; de Bakker, Paul/B-8730-2009;
Onland-Moret, N. Charlotte/G-9185-2011; Thorand, Barbara/B-5349-2014
OI Kleber, Marcus/0000-0003-0663-7275; Davey Smith,
George/0000-0002-1407-8314; Stanton, Alice/0000-0002-4961-165X;
Wijmenga, Cisca/0000-0002-5635-1614; Johnson, Toby/0000-0002-5998-3270;
Karczewski, Konrad/0000-0003-2878-4671; Padmanabhan,
Sandosh/0000-0003-3869-5808; Ramachandran, Vasan/0000-0001-7357-5970;
Gieger, Christian/0000-0001-6986-9554; Watkins,
Hugh/0000-0002-5287-9016; Pankow, James/0000-0001-7076-483X; van der
Schouw, Yvonne/0000-0002-4605-435X; Shah, Sonia/0000-0001-5860-4526;
Price, Thomas/0000-0001-7356-2109; Jarvik, Gail/0000-0002-6710-8708;
Gaunt, Tom/0000-0003-0924-3247; de Bakker, Paul/0000-0001-7735-7858;
Thorand, Barbara/0000-0002-8416-6440
FU British Heart Foundation [FS/11/35/28871, FS/12/33/29561, FS/12/8/29377,
FS/14/12/30540, PG/07/085/23349, PG/09/022/26739, SP/08/002/24118];
Medical Research Council [G0802432, G0902313, G9521010, MC_UU_12013/1,
MC_UU_12013/8, MR/K006584/1, MR/K013351/1]; NCATS NIH HHS [UL1 TR000064,
UL1 TR000124]; NHLBI NIH HHS [R01 HL074730]; NIA NIH HHS [R01 AG016592,
R01 AG021917, R37 AG011099]; NIDDK NIH HHS [P30 DK063491, P30 DK072488];
NIGMS NIH HHS [U01 GM074492]; Wellcome Trust [090532]
NR 114
TC 50
Z9 51
U1 3
U2 29
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD MAR 6
PY 2014
VL 94
IS 3
BP 349
EP 360
DI 10.1016/j.ajhg.2013.12.016
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA AC6DK
UT WOS:000332611400009
PM 24560520
ER
PT J
AU Mihaylova, MM
Sabatini, DM
Yilmaz, OH
AF Mihaylova, Maria M.
Sabatini, David M.
Yilmaz, Oemer H.
TI Dietary and Metabolic Control of Stem Cell Function in Physiology and
Cancer
SO CELL STEM CELL
LA English
DT Review
ID HIGH-FAT DIET; ACUTE MYELOGENOUS LEUKEMIA; RESTRICTED KETOGENIC DIET;
IN-VITRO EXPANSION; HEMATOPOIETIC STEM; SELF-RENEWAL; CALORIE
RESTRICTION; SKELETAL-MUSCLE; ENERGY-METABOLISM; OXIDATIVE STRESS
AB Organismal diet has a profound impact on tissue homeostasis and health in mammals. Adult stem cells are a keystone of tissue homeostasis that alters tissue composition by balancing self-renewal and differentiation divisions. Because somatic stem cells may respond to shifts in organismal physiology to orchestrate tissue remodeling and some cancers are understood to arise from transformed stem cells, there is a likely possibility that organismal diet, stem cell function, and cancer initiation are interconnected. Here we will explore the emerging effects of diet on nutrient-sensing pathways active in mammalian tissue stem cells and their relevance to normal and cancerous growth.
C1 [Mihaylova, Maria M.; Sabatini, David M.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
[Mihaylova, Maria M.; Sabatini, David M.] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
[Mihaylova, Maria M.; Sabatini, David M.] Broad Inst Harvard & MIT, Seven Cambridge Ctr, Cambridge, MA 02142 USA.
[Mihaylova, Maria M.; Sabatini, David M.; Yilmaz, Oemer H.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
[Mihaylova, Maria M.; Sabatini, David M.; Yilmaz, Oemer H.] MIT, Dept Biol, Cambridge, MA 02139 USA.
[Yilmaz, Oemer H.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Yilmaz, Oemer H.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Sabatini, DM (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
EM sabatini@wi.mit.edu; ohyilmaz@mit.edu
FU NIH [CA129105, CA103866, AI047389]; Koch Institute Frontier Research
Program; Ellison Medical Foundation; K99/R00 Pathway to Independence
Award from the NIH/NIA [AG045144]; CSIBD from NIDDK/NIH [DK043351]
FX We apologize for being unable to discuss multiple primary studies due to
references and space limitations. M. M. is a Robert Black Fellow of the
Damon Runyon Cancer Research Foundation, DRG-2146-13. D. M. S. is an
investigator of the Howard Hughes Medical Institute and is supported by
awards from the NIH (CA129105, CA103866, and AI047389), Koch Institute
Frontier Research Program, and the Ellison Medical Foundation. O.H.Y. is
supported by a K99/R00 Pathway to Independence Award from the NIH/NIA
AG045144 and a CSIBD grant from the NIDDK/NIH (DK043351).
NR 143
TC 30
Z9 31
U1 2
U2 25
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
EI 1875-9777
J9 CELL STEM CELL
JI Cell Stem Cell
PD MAR 6
PY 2014
VL 14
IS 3
BP 292
EP 305
DI 10.1016/j.stem.2014.02.008
PG 14
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA AC5AR
UT WOS:000332533400007
PM 24607404
ER
PT J
AU Choudhuri, K
Llodra, J
Roth, EW
Tsai, J
Gordo, S
Wucherpfennig, KW
Kam, LC
Stokes, DL
Dustin, ML
AF Choudhuri, Kaushik
Llodra, Jaime
Roth, Eric W.
Tsai, Jones
Gordo, Susana
Wucherpfennig, Kai W.
Kam, Lance C.
Stokes, David L.
Dustin, Michael L.
TI Polarized release of T-cell-receptor-enriched microvesicles at the
immunological synapse
SO NATURE
LA English
DT Article
ID SUPRAMOLECULAR ACTIVATION CLUSTER; ELECTRON TOMOGRAPHY; CLASS-II;
PROTEIN; COMPLEX; PROLIFERATION; MICROSCOPY; MOLECULES; DYNAMICS;
ADHESION
AB The recognition events that mediate adaptive cellular immunity and regulate antibody responses depend on intercellular contacts between T cells and antigen-presenting cells (APCs)(1). T-cell signalling is initiated at these contacts when surface-expressed T-cell receptors (TCRs) recognize peptide fragments (antigens) of pathogens bound to major histocompatibility complex molecules (pMHC) on APCs. This, along with engagement of adhesion receptors, leads to the formation of a specialized junction between T cells and APCs, known as the immunological synapse(2), which mediates efficient delivery of effector molecules and intercellular signals across the synaptic cleft(3). T-cell recognition of pMHC and the adhesion ligand intercellular adhesion molecule-1 (ICAM-1) on supported planar bilayers recapitulates the domain organization of the immunological synapse(4,5), which is characterized by central accumulation of TCRs(5), adjacent to a secretory domain(2), both surrounded by an adhesive ring(4,5). Although accumulation of TCRs at the immunological synapse centre correlates with T-cell function(4), this domain is itself largely devoid of TCR signalling activity(5,6), and is characterized by an unexplained immobilization of TCR-pMHC complexes relative to the highly dynamic immunological synapse periphery(4,5). Here we show that centrally accumulated TCRs are located on the surface of extracellular microvesicles that bud at the immunological synapse centre. Tumour susceptibility gene 101 (TSG101)(6) sorts TCRs for inclusion in microvesicles, whereas vacuolar protein sorting 4 (VPS4)(7,8) mediates scission of microvesicles from the T-cell plasma membrane. The human immunodeficiency virus polyprotein Gag co-opts this process for budding of virus-like particles. B cells bearing cognate pMHC receive TCRs from T cells and initiate intracellular signals in response to isolated synaptic microvesicles. We conclude that the immunological synapse orchestrates TCR sorting and release in extracellular microvesicles. These microvesicles deliver transcellular signals across antigen-dependent synapses by engaging cognate pMHC on APCs.
C1 [Choudhuri, Kaushik] Skirball Inst Biomol Med, Program Mol Pathogenesis, Helen L & Martin S Kimmel Ctr Biol & Med, New York, NY 10016 USA.
[Llodra, Jaime; Stokes, David L.] Skirball Inst Biomol Med, Program Struct Biol, Helen L & Martin S Kimmel Ctr Biol & Med, New York, NY 10016 USA.
[Roth, Eric W.] Northwestern Univ, Atom & Nanoscale Characterizat Expt Ctr, Evanston, IL 60208 USA.
[Tsai, Jones; Kam, Lance C.] Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA.
[Gordo, Susana; Wucherpfennig, Kai W.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA.
[Gordo, Susana; Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Program Immunol, Boston, MA 02215 USA.
[Stokes, David L.] New York Struct Biol Ctr, New York, NY 10027 USA.
[Dustin, Michael L.] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA.
[Dustin, Michael L.] Univ Oxford, Kennedy Inst Rheumatol, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Oxford OX3 7FY, England.
RP Dustin, ML (reprint author), NYU, Sch Med, Dept Pathol, 540 First Ave, New York, NY 10016 USA.
EM stokes@nyu.edu; michael.dustin@kennedy.ox.ac.uk
OI Dustin, Michael/0000-0003-4983-6389
FU New York Structural Biology Center; Cancer Research Institute; NIH
[K99AI093884, AI043542, AI045757, AI055037, AI088377, AI093884,
EY016586]; Wellcome Trust; Kennedy Trust
FX We thank G. Schutz for suggesting the photoactivation experiment, H.
Chen for microfabrication, W. Sundquist for providing Gag-GFP, VPS4-GFP
and VPS4dn-GFP constructs, P. Bieniasz for Gag-mCherry, Gag Delta
L-mCherry, ALIX-GFP and CHMP4B-GFP constructs, the New York Structural
Biology Center for electron microscopy tomography, support and
instrumentation and members of the Dustin laboratory for helpful
discussions and contributions of reagents. We thank J. Nance for the
gift of biotinylated duramycin-linked biotin. This work was supported in
part by a Cancer Research Institute fellowship and NIH grant K99AI093884
(K.C.), a Wellcome Trust Principal Research Fellowship (M.L.D.), a
Kennedy Trust Senior Research Fellowship (M.L.D.) and NIH grants
AI043542, AI045757, AI055037, AI088377, AI093884 and EY016586
(Nanomedicine Development Center).
NR 39
TC 93
Z9 94
U1 5
U2 64
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAR 6
PY 2014
VL 507
IS 7490
BP 118
EP +
DI 10.1038/nature12951
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC0ZQ
UT WOS:000332224400054
PM 24487619
ER
PT J
AU Jan, RK
Lin, JC
McLaren, DG
Kirk, IJ
Kydd, RR
Russell, BR
AF Jan, Reem K.
Lin, Joanne C.
McLaren, Donald G.
Kirk, Ian J.
Kydd, Rob R.
Russell, Bruce R.
TI The effects of methyphenidate on cognitive contron in active
methamphetamine dependence using functional magnetic resonance imaging
SO FRONTIERS IN PSYCHIATRY
LA English
DT Article
DE cognitive control; BOLD; drug dependence; fMRI; methamphetamine;
methylphenidate; Stroop
AB Methamphetamine (MA) dependence is associated with cognitive deficits. Methylphenidate (MPH) has been shown to improve inhibitory control in healthy and cocaine-dependent subjects. This study aimed to understand the neurophysiological effects before and after acute MPH administration in active MA-dependent and control subjects. Fifteen MA-dependent and 18 control subjects aged 18-46 years were scanned using functional magnetic resonance imaging before and after either a single oral dose of MPH (18 mg) or placebo while performing a color-word Stroop task. Baseline accuracy was lower (p < 0.026) and response time (RT) was longer (p < 0.0001) for the incongruent compared to congruent condition, demonstrating the task probed cognitive control. Increased activation of the dorsolateral prefrontal cortex (DLPFC) and parietal cortex during the incongruent and Stroop effect conditions, respectively was observed in MA-dependent compared to control subjects (p < 0.05), suggesting the need to recruit neural resources within these regions for conflict resolution. Post- compared to pre-MPH treatment, increased RT and DLPFC activation for the Stroop effect were observed in MA-dependent subjects (p < 0.05). In comparison to MPH-treated controls and placebo-treated MA-dependent subjects, MPH-treated MA-dependent subjects showed decreased activation of parietal and occipital regions during the incongruent and Stroop effect conditions (p < 0.05). These findings suggest that in MA-dependent subjects, MPH facilitated increased recruitment of the DLPFC for Stroop conflict resolution, and a decreased need for recruitment of neural resources in parietal and occipital regions compared to the other groups, while maintaining a comparable level of task performance to that achieved pre-drug administration. Due to the small sample size, the results from this study are preliminary; however, they inform us about the effects of MPH on the neural correlates of cognitive control in active MA-dependent subjects.
C1 [Jan, Reem K.; Lin, Joanne C.; Russell, Bruce R.] Univ Auckland, Sch Pharm, Auckland, New Zealand.
[Jan, Reem K.; Lin, Joanne C.; Kirk, Ian J.; Kydd, Rob R.; Russell, Bruce R.] Univ Auckland, Ctr Brain Res, Auckland, New Zealand.
[McLaren, Donald G.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA.
[McLaren, Donald G.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[McLaren, Donald G.] Harvard Med Sch, Boston, MA USA.
[Kirk, Ian J.] Univ Auckland, Dept Psychol, Auckland, New Zealand.
[Kydd, Rob R.] Univ Auckland, Dept Psychol Med, Auckland, New Zealand.
RP Russell, BR (reprint author), Univ Auckland, Fac Med & Hlth Sci, Sch Pharm, Private Bag 92019, Auckland 1142, New Zealand.
EM b.russell@auckland.ac.nz
FU New Zealand Pharmacy Education Research Foundation [208]; University of
Auckland Faculty Development Research Fund; Oakley Mental Health
Research Foundation; University of Auckland Doctoral Scholarship; New
Zealand Federation of Graduate Women
FX This paper was supported by the New Zealand Pharmacy Education Research
Foundation Grant Number 208, the University of Auckland Faculty
Development Research Fund, and the Oakley Mental Health Research
Foundation. Reem K. Jan was supported by the University of Auckland
Doctoral Scholarship and the New Zealand Federation of Graduate Women.
The authors thank Nicolas McNair, Mark Jenkinson, Avinesh Pillai, Chris
Triggs, Maree Jensen, Peta Hardley, Jari Tiihonen, Janie Sheridan,
Louise Curley, and Michelle Gordon, for their involvement invarious
aspects of the trial, including planning, administration, subject
recruitment or advice on statistical data analysis.
NR 131
TC 3
Z9 3
U1 0
U2 2
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-0640
J9 FRONT PSYCHIATRY
JI Front. Psychiatry
PD MAR 6
PY 2014
VL 5
AR 20
DI 10.3389/fpsyt.2014.00020
PG 18
WC Psychiatry
SC Psychiatry
GA V46RF
UT WOS:000209900600001
PM 24639656
ER
PT J
AU Fagan, AM
Xiong, CJ
Jasielec, MS
Bateman, RJ
Goate, AM
Benzinger, TLS
Ghetti, B
Martins, RN
Masters, CL
Mayeux, R
Ringman, JM
Rossor, MN
Salloway, S
Schofield, PR
Sperling, RA
Marcus, D
Cairns, NJ
Buckles, VD
Ladenson, JH
Morris, JC
Holtzman, DM
AF Fagan, Anne M.
Xiong, Chengjie
Jasielec, Mateusz S.
Bateman, Randall J.
Goate, Alison M.
Benzinger, Tammie L. S.
Ghetti, Bernardino
Martins, Ralph N.
Masters, Colin L.
Mayeux, Richard
Ringman, John M.
Rossor, Martin N.
Salloway, Stephen
Schofield, Peter R.
Sperling, Reisa A.
Marcus, Daniel
Cairns, Nigel J.
Buckles, Virginia D.
Ladenson, Jack H.
Morris, John C.
Holtzman, David M.
CA Dominantly Inherited Alzheimer Net
TI Longitudinal Change in CSF Biomarkers in Autosomal-Dominant Alzheimer's
Disease
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID MILD COGNITIVE IMPAIRMENT; CEREBROSPINAL-FLUID TAU;
AMYLOID-BETA-PROTEIN; AUTOPSY-CONFIRMED DEMENTIA; QUALITY-CONTROL
PROGRAM; A-BETA; PRESENILIN-1 MUTATION; LEWY BODIES; IN-VIVO;
CLINICAL-DIAGNOSIS
AB Clinicopathological evidence suggests that the pathology of Alzheimer's disease ( AD) begins many years before the appearance of cognitive symptoms. Biomarkers are required to identify affected individuals during this asymptomatic ("preclinical") stage to permit intervention with potential disease-modifying therapies designed to preserve normal brain function. Studies of families with autosomal-dominant AD (ADAD) mutations provide a unique and powerful means to investigate AD biomarker changes during the asymptomatic period. In this biomarker study, we collected cerebrospinal fluid (CSF), plasma, and in vivo amyloid imaging cross-sectional data at baseline in individuals from ADAD families enrolled in the Dominantly Inherited Alzheimer Network. Our study revealed reduced concentrations of CSF amyloid-beta(1-42) (A beta(1-42)) associated with the presence of Ab plaques, and elevated concentrations of CSF tau, ptau(181) (phosphorylated tau(181)), and VILIP-1 (visinin-like protein-1), markers of neurofibrillary tangles and neuronal injury/death, in asymptomatic mutation carriers 10 to 20 years before their estimated age at symptom onset (EAO) and before the detection of cognitive deficits. When compared longitudinally, however, the concentrations of CSF biomarkers of neuronal injury/death within individuals decreased after their EAO, suggesting a slowing of acute neurodegenerative processes with symptomatic disease progression. These results emphasize the importance of longitudinal, within-person assessment when modeling biomarker trajectories across the course of the disease. If corroborated, this pattern may influence the definition of a positive neurodegenerative biomarker outcome in clinical trials.
C1 [Fagan, Anne M.; Bateman, Randall J.; Goate, Alison M.; Cairns, Nigel J.; Buckles, Virginia D.; Morris, John C.; Holtzman, David M.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Fagan, Anne M.; Xiong, Chengjie; Jasielec, Mateusz S.; Bateman, Randall J.; Goate, Alison M.; Benzinger, Tammie L. S.; Marcus, Daniel; Cairns, Nigel J.; Buckles, Virginia D.; Morris, John C.; Holtzman, David M.] Washington Univ, Sch Med, Knight Alzheimers Dis Res Ctr, St Louis, MO 63110 USA.
[Xiong, Chengjie; Jasielec, Mateusz S.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.
[Goate, Alison M.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Benzinger, Tammie L. S.; Marcus, Daniel] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA.
[Ghetti, Bernardino] Indiana Univ, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA.
[Martins, Ralph N.] Edith Cowan Univ, WA Ctr Alzheimers Res & Care, Perth, WA 6009, Australia.
[Masters, Colin L.] Univ Melbourne, Mental Hlth Res Inst, Melbourne, Vic 3052, Australia.
[Mayeux, Richard] Columbia Univ, Taub Inst, Dept Neurol, New York, NY 10032 USA.
[Mayeux, Richard] Columbia Univ, Sergievsky Ctr, New York, NY 10032 USA.
[Ringman, John M.] Univ Calif Los Angeles, Mary S Easton Ctr Alzheimers Dis Res, Dept Neurol, Los Angeles, CA 90095 USA.
[Rossor, Martin N.] UCL, Dementia Res Ctr, London WC1N 3BG, England.
[Salloway, Stephen] Brown Univ, Butler Hosp, Warren Alpert Med Sch, Dept Neurol, Providence, RI 02906 USA.
[Salloway, Stephen] Brown Univ, Butler Hosp, Warren Alpert Med Sch, Dept Psychiat, Providence, RI 02906 USA.
[Schofield, Peter R.] Neurosci Res Australia, Sydney, NSW 2031, Australia.
[Schofield, Peter R.] Univ New S Wales, Sch Med Sci, Sydney, NSW 2031, Australia.
[Sperling, Reisa A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Brigham & Womens Hosp, Boston, MA 02129 USA.
[Cairns, Nigel J.; Ladenson, Jack H.; Morris, John C.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
RP Fagan, AM (reprint author), Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
EM fagana@neuro.wustl.edu
FU DIAN [U19 AG032438]; cooperative agreement grant [NCRAD U24 AG21886];
National Institute on Aging (NIA); DIAN Pharma Consortium
FX Data collection and sharing for this project was supported by DIAN (U19
AG032438; to R.J.B., T.L.S. B., V.D.B., N.J.C., A.M.F., B.G., A.M.G.,
D.M.H., M.S.J., D.M., RN.M., C.L.M., R.M., J.C.M., J.M.R., M.N.R., S.S.,
P.R.S., R.A.S., and C.X.) and a cooperative agreement grant (NCRAD U24
AG21886) funded by the National Institute on Aging (NIA), the DIAN
Pharma Consortium [Alzheimer's Immunotherapy Program (Janssen Alzheimer
Immunotherapy and Pfizer Inc. Alliance), Biogen Idec Inc., Eisai Inc.,
Elan Pharmaceuticals Inc., Eli Lilly and Company, En Vivo
Pharmaceuticals, Genentech Inc., F. Hoffman-La Roche Ltd., Mithridion
Inc., Novartis International AG, Pfizer Inc., and Sanofi-Aventis Groupe]
(to R.J.B., T.L.S.B., V.D.B., A.M.F., A.M.G., and C.X.), and in part by
R01 EB009352 (to D.M.), P30 NS048056 (to D.M.), P50AG016750 (to J.M.R.),
the National Institute for Health Research Queen Square Dementia
Biomedical Research Unit (to M.N.R.), and the JO & JR Wicking Trust
grants 13026 and 20821 (to P.R.S.). This article has been reviewed by
DIAN Study investigators for scientific content and consistency of data
interpretation with previous DIAN Study presentations/publications.
NR 103
TC 35
Z9 35
U1 2
U2 16
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD MAR 5
PY 2014
VL 6
IS 226
AR 226ra30
DI 10.1126/scitranslmed.3007901
PG 16
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA AC6JV
UT WOS:000332629500003
PM 24598588
ER
PT J
AU Veeraraghavalu, K
Zhang, C
Zhang, XQ
Tanzi, RE
Sisodia, SS
AF Veeraraghavalu, Karthikeyan
Zhang, Can
Zhang, Xiaoqiong
Tanzi, Rudolph E.
Sisodia, Sangram S.
TI Age-Dependent, Non-Cell-Autonomous Deposition of Amyloid from Synthesis
of beta-Amyloid by Cells Other Than Excitatory Neurons
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE amyloid deposition; APP; dementia; mouse model; neurodegeneration;
presenilin
ID FAMILIAL ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; MUTANT PRESENILIN-1;
MESSENGER-RNAS; EXPRESSION; LOCALIZATION; MODELS; BRAIN
AB Rare, familial, early-onset autosomal dominant forms of familial Alzheimer's disease (FAD) are caused by mutations in genes encoding beta-amyloid (A beta) precursor protein (APP), presenilin-1 (PS1), and presenilin-2. Each of these genes is expressed ubiquitously throughout the CNS, but a widely held view is that excitatory neurons are the primary (or sole) source of the A beta peptides that promote synaptic dysfunction and neurodegeneration. These efforts notwithstanding, APP and the enzymes required for A beta production are synthesized by manyadditional cell types, and the degree to which those cells contribute to the production of A beta that drives deposition in the CNS has not been tested. We generated transgenic mice in which expression of an ubiquitously expressed, FAD-linked mutant PSEN1 gene was selectively inactivated within postnatal forebrain excitatory neurons, with continued synthesis in all other cells in the CNS. When combined with an additional transgene encoding an FAD-linked APP "Swedish" variant that is synthesized broadly within the CNS, cerebral A beta deposition during aging was found to be unaffected relative to mice with continued mutant PS1 synthesis in excitatory neurons. Thus, A beta accumulation is non-cell autonomous, with the primary age-dependent contribution to cerebral A beta deposition arising from mutant PS1-dependent cleavage of APP within cells other than excitatory neurons.
C1 [Veeraraghavalu, Karthikeyan; Zhang, Xiaoqiong; Sisodia, Sangram S.] Univ Chicago, Dept Neurobiol, Chicago, IL 60637 USA.
[Zhang, Can; Tanzi, Rudolph E.] Massachusetts Gen Hosp, Massachusetts Gen Inst Neurodegenerat Dis, Dept Neurol, Genet & Aging Res Unit, Charlestown, MA 02129 USA.
[Zhang, Can; Tanzi, Rudolph E.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
RP Sisodia, SS (reprint author), Univ Chicago, Dept Neurobiol, 947 East 58th St,AB 308, Chicago, IL 60637 USA.
EM ssisodia@bsd.uchicago.edu
FU National Institutes of Health [AG021494, AG027854]; Cure Alzheimer's
Fund; Edward H. Levi Fund; Adler Foundation
FX This work was supported by National Institutes of Health Grants AG021494
and AG027854 (S.S.S.), the Cure Alzheimer's Fund (S.S.S.), the Edward H.
Levi Fund (K.V.), and the Adler Foundation (K.V., S.S.S.). We thank Dr.
Vytas Bindokas, Microscopy Core Facility, for expert support with image
analysis.
NR 16
TC 8
Z9 10
U1 0
U2 6
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAR 5
PY 2014
VL 34
IS 10
BP 3668
EP 3673
DI 10.1523/JNEUROSCI.5079-13.2014
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA AC7HN
UT WOS:000332698900020
PM 24599465
ER
PT J
AU Begum, G
Yan, HQ
Li, L
Singh, A
Dixon, CE
Sun, D
AF Begum, Gulnaz
Yan, Hong Q.
Li, Liaoliao
Singh, Amneet
Dixon, C. Edward
Sun, Dandan
TI Docosahexaenoic Acid Reduces ER Stress and Abnormal Protein Accumulation
and Improves Neuronal Function Following Traumatic Brain Injury
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE amyloid precursor protein; controlled cortical impact injury;
docosahexaenoic acid; phosphorylated tau; unfolded protein response
ID ENDOPLASMIC-RETICULUM STRESS; DIFFUSE AXONAL INJURY; AMYLOID PRECURSOR
PROTEIN; CORTICAL IMPACT MODEL; K+-CL-COTRANSPORTER; CELL-DEATH;
CHEMICAL CHAPERONES; ASTROCYTES; ISCHEMIA; BETA
AB In this study, we investigated the development of endoplasmic reticulum (ER) stress after traumatic brain injury (TBI) and the efficacy of post-TBI administration of docosahexaenoic acid (DHA) in reducing ER stress. TBI was induced by cortical contusion injury in Sprague-Dawley rats. Either DHA (16 mg/kg in DMSO) or vehicle DMSO (1 ml/kg) was administered intraperitoneally at 5 min after TBI, followed by a daily dose for 3-21 d. TBI triggered sustained expression of the ER stress marker proteins including phosphorylated eukaryotic initiation factor-2 alpha, activating transcription factor 4, inositol requiring kinase 1, and C/EBP homologous protein in the ipsilateral cortex at 3-21 d after TBI. The prolonged ER stress was accompanied with an accumulation of abnormal ubiquitin aggregates and increased expression of amyloid precursor protein (APP) and phosphorylated tau (p-Tau) in the frontal cortex after TBI. The ER stress marker proteins were colocalized with APP accumulation in the soma. Interestingly, administration of DHA attenuated all ER stress marker proteins and reduced the accumulation of both ubiquitinated proteins and APP/p-Tau proteins. In addition, the DHA-treated animals exhibited early recovery of their sensorimotor function after TBI. In summary, our study demonstrated that TBI induces a prolonged ER stress, which is positively correlated with abnormal APP accumulation. The sustained ER stress may play a role in chronic neuronal damage after TBI. Our findings illustrate that post-TBI administration of DHA has therapeutic potentials in reducing ER stress, abnormal protein accumulation, and neurological deficits.
C1 [Begum, Gulnaz; Li, Liaoliao; Singh, Amneet; Sun, Dandan] Univ Pittsburgh, Brain Trauma Res Ctr, Dept Neurol, Pittsburgh, PA 15213 USA.
[Yan, Hong Q.; Dixon, C. Edward] Univ Pittsburgh, Brain Trauma Res Ctr, Dept Neurosurg, Pittsburgh, PA 15213 USA.
[Dixon, C. Edward; Sun, Dandan] Geriatr Res Educ & Clin Ctr, Vet Affairs Pittsburgh Hlth Care Syst, Pittsburgh, PA 15213 USA.
RP Sun, D (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, S 598 S Biomedical Sci Tower,3500 Terrace St, Pittsburgh, PA 15213 USA.
EM sund@upmc.edu
FU University of Pittsburgh Neurology Departmental startup funds;
University of Pittsburgh Medical Center endowed Chair Professorship on
Brain Disorder Diseases; United States Department of Veterans Affairs VA
RRD [B6761R]
FX This work was supported in part by University of Pittsburgh Neurology
Departmental startup funds and University of Pittsburgh Medical Center
endowed Chair Professorship on Brain Disorder Diseases (D.S.) and the
United States Department of Veterans Affairs VA RR&D#B6761R Grant
(C.E.D.).
NR 70
TC 24
Z9 27
U1 1
U2 9
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD MAR 5
PY 2014
VL 34
IS 10
BP 3743
EP 3755
DI 10.1523/JNEUROSCI.2872-13.2014
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA AC7HN
UT WOS:000332698900027
PM 24599472
ER
PT J
AU Heck, A
Fastenrath, M
Ackermann, S
Auschra, B
Bickel, H
Coynel, D
Gschwind, L
Jessen, F
Kaduszkiewicz, H
Maier, W
Milnik, A
Pentzek, M
Riedel-Heller, SG
Ripke, S
Spalek, K
Sullivan, P
Vogler, C
Wagner, M
Weyerer, S
Wolfsgruber, S
de Quervain, DJF
Papassotiropoulos, A
AF Heck, Angela
Fastenrath, Matthias
Ackermann, Sandra
Auschra, Bianca
Bickel, Horst
Coynel, David
Gschwind, Leo
Jessen, Frank
Kaduszkiewicz, Hanna
Maier, Wolfgang
Milnik, Annette
Pentzek, Michael
Riedel-Heller, Steffi G.
Ripke, Stephan
Spalek, Klara
Sullivan, Patrick
Vogler, Christian
Wagner, Michael
Weyerer, Siegfried
Wolfsgruber, Steffen
de Quervain, Dominique J. -F.
Papassotiropoulos, Andreas
TI Converging Genetic and Functional Brain Imaging Evidence Links Neuronal
Excitability to Working Memory, Psychiatric Disease, and Brain Activity
SO NEURON
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; BIPOLAR DISORDER; SET ANALYSIS; RISK LOCI;
SCHIZOPHRENIA; SYSTEM; CEREBELLUM; REGISTRATION; CIRCUITRY; COGNITION
AB Working memory, the capacity of actively maintaining task-relevant information during a cognitive task, is a heritable trait. Working memory deficits are characteristic for many psychiatric disorders. We performed genome-wide gene set enrichment analyses in multiple independent data sets of young and aged cognitively healthy subjects (n = 2,824) and in a large schizophrenia case-control sample (n = 32,143). The voltage-gated cation channel activity gene set, consisting of genes related to neuronal excitability, was robustly linked to performance in working memory-related tasks across ages and to schizophrenia. Functional brain imaging in 707 healthy participants linked this gene set also to working memory-related activity in the parietal cortex and the cerebellum. Gene set analyses may help to dissect the molecular underpinnings of cognitive dimensions, brain activity, and psychopathology.
C1 [Heck, Angela; Fastenrath, Matthias; Ackermann, Sandra; Auschra, Bianca; Coynel, David; Gschwind, Leo; Milnik, Annette; Vogler, Christian; Weyerer, Siegfried; Papassotiropoulos, Andreas] Univ Basel, Dept Psychol, Div Mol Neurosci, CH-4055 Basel, Switzerland.
[Heck, Angela; Milnik, Annette; Vogler, Christian; de Quervain, Dominique J. -F.; Papassotiropoulos, Andreas] Univ Basel, Dept Psychol, Psychiat Univ Clin, CH-4055 Basel, Switzerland.
[Fastenrath, Matthias; Coynel, David; Gschwind, Leo; Spalek, Klara; de Quervain, Dominique J. -F.] Univ Basel, Dept Psychol, Div Cognit Neurosci, CH-4055 Basel, Switzerland.
[Bickel, Horst] Tech Univ Munich, Dept Psychiat, D-85748 Munich, Germany.
[Jessen, Frank; Maier, Wolfgang; Wagner, Michael; Wolfsgruber, Steffen] Univ Bonn, Dept Psychiat, D-53105 Bonn, Germany.
[Jessen, Frank; Maier, Wolfgang; Wagner, Michael; Wolfsgruber, Steffen] German Ctr Neurogenerat Dis, DZNE, D-53105 Bonn, Germany.
[Kaduszkiewicz, Hanna] Univ Med Ctr Hamburg Eppendorf, Ctr Psychosocial Med, Dept Primary Med Care, D-20246 Hamburg, Germany.
[Pentzek, Michael] Univ Dusseldorf, Fac Med, Inst Gen Practice, D-40225 Dusseldorf, Germany.
[Riedel-Heller, Steffi G.] Univ Leipzig, Fac Med, Inst Social Med Occupat Hlth & Publ Hlth, D-04103 Leipzig, Germany.
[Ripke, Stephan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Sullivan, Patrick] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Weyerer, Siegfried] Cent Inst Mental Hlth, D-68159 Mannheim, Germany.
[Papassotiropoulos, Andreas] Univ Basel, Dept Biozentrum, Life Sci Training Facil, CH-4056 Basel, Switzerland.
[Papassotiropoulos, Andreas] Univ Basel, Transfac Res Platform, CH-4012 Basel, Switzerland.
RP Heck, A (reprint author), Univ Basel, Dept Psychol, Div Mol Neurosci, CH-4055 Basel, Switzerland.
EM angela.heck@unibas.ch; andreas.papas@unibas.ch
RI Wagner, Michael/E-2325-2011;
OI Wagner, Michael/0000-0003-2589-6440; Coynel, David/0000-0001-5028-5807;
Milnik, Annette/0000-0002-3933-3289
FU Swiss National Science Foundation [CRSI33_130080]; European Union
[HEALTH-F4-2009-242257]; National Center for Competence in Research
SYNAPSY; German Research Network on Dementia (KND); German Research
Network on Degenerative Dementia (KNDD), German Federal Ministry of
Education and Research [01GI0420, 01GI0711]
FX We thank Elmar Merkle, Christoph Stippich, and Oliver Bieri for granting
access to the fMRI facilities of the University Hospital Basel. This
work was funded by the Swiss National Science Foundation (Sinergia grant
CRSI33_130080 to D.J.-F.d.Q. and A.P.), by the 7th framework programme
of the European Union (ADAMS project, HEALTH-F4-2009-242257), by the
National Center for Competence in Research SYNAPSY, and by the German
Research Network on Dementia (KND) and the German Research Network on
Degenerative Dementia (KNDD), German Federal Ministry of Education and
Research grants 01GI0420 and 01GI0711.
NR 51
TC 28
Z9 28
U1 2
U2 13
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
EI 1097-4199
J9 NEURON
JI Neuron
PD MAR 5
PY 2014
VL 81
IS 5
BP 1203
EP 1213
DI 10.1016/j.neuron.2014.01.010
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA AC4YH
UT WOS:000332526700021
PM 24529980
ER
PT J
AU Neuille, M
El Shamieh, S
Orhan, E
Michiels, C
Antonio, A
Lancelot, ME
Condroyer, C
Bujakowska, K
Poch, O
Sahel, JA
Audo, I
Zeitz, C
AF Neuille, Marion
El Shamieh, Said
Orhan, Elise
Michiels, Christelle
Antonio, Aline
Lancelot, Marie-Elise
Condroyer, Christel
Bujakowska, Kinga
Poch, Olivier
Sahel, Jose-Alain
Audo, Isabelle
Zeitz, Christina
TI Lrit3 Deficient Mouse (nob6): A Novel Model of Complete Congenital
Stationary Night Blindness (cCSNB)
SO PLOS ONE
LA English
DT Article
ID RICH REPEAT PROTEIN; METABOTROPIC GLUTAMATE-RECEPTOR; OPTICAL COHERENCE
TOMOGRAPHY; ROD BIPOLAR CELLS; CGMP PHOSPHODIESTERASE;
SYNAPTIC-TRANSMISSION; RETINAL DEGENERATION; MAMMALIAN RETINA; LIGHT
RESPONSE; BETA-SUBUNIT
AB Mutations in LRIT3, coding for a Leucine-Rich Repeat, immunoglobulin-like and transmembrane domains 3 protein lead to autosomal recessive complete congenital stationary night blindness (cCSNB). The role of the corresponding protein in the ON-bipolar cell signaling cascade remains to be elucidated. Here we genetically and functionally characterize a commercially available Lrit3 knock-out mouse, a model to study the function and the pathogenic mechanism of LRIT3. We confirm that the insertion of a Bgeo/Puro cassette in the knock-out allele introduces a premature stop codon, which presumably codes for a non-functional protein. The mouse line does not harbor other mutations present in common laboratory mouse strains or in other known cCSNB genes. Lrit3 mutant mice exhibit a so-called no b-wave (nob) phenotype with lacking or severely reduced b-wave amplitudes in the scotopic and photopic electroretinogram (ERG), respectively. Optomotor tests reveal strongly decreased optomotor responses in scotopic conditions. No obvious fundus auto-fluorescence or histological retinal structure abnormalities are observed. However, spectral domain optical coherence tomography (SD-OCT) reveals thinned inner nuclear layer and part of the retina containing inner plexiform layer, ganglion cell layer and nerve fiber layer in these mice. To our knowledge, this is the first time that SD-OCT technology is used to characterize an animal model for CSNB. This phenotype is noted at 6 weeks and at 6 months. The stationary nob phenotype of mice lacking Lrit3, which we named nob6, confirms the findings previously reported in patients carrying LRIT3 mutations and is similar to other cCSNB mouse models. This novel mouse model will be useful for investigating the pathogenic mechanism(s) associated with LRIT3 mutations and clarifying the role of LRIT3 in the ON-bipolar cell signaling cascade.
C1 [Neuille, Marion; El Shamieh, Said; Orhan, Elise; Michiels, Christelle; Antonio, Aline; Lancelot, Marie-Elise; Condroyer, Christel; Bujakowska, Kinga; Sahel, Jose-Alain; Audo, Isabelle; Zeitz, Christina] INSERM, U968, Paris, France.
[Neuille, Marion; El Shamieh, Said; Orhan, Elise; Michiels, Christelle; Antonio, Aline; Lancelot, Marie-Elise; Condroyer, Christel; Bujakowska, Kinga; Sahel, Jose-Alain; Audo, Isabelle; Zeitz, Christina] CNRS, UMR 7210, Paris, France.
[Neuille, Marion; El Shamieh, Said; Orhan, Elise; Michiels, Christelle; Antonio, Aline; Lancelot, Marie-Elise; Condroyer, Christel; Bujakowska, Kinga; Sahel, Jose-Alain; Audo, Isabelle; Zeitz, Christina] Univ Paris 06, Univ Sorbonne, UMR S 968, Inst Vis, Paris, France.
[Antonio, Aline; Sahel, Jose-Alain; Audo, Isabelle] Ctr Hosp Natl Ophtalmol Quinze Vingts, INSERM DHOS CIC 503, Paris, France.
[Bujakowska, Kinga] Massachusetts Eye & Ear Infirm, Ocular Genom Inst, Boston, MA 02114 USA.
[Poch, Olivier] CNRS, UMR 7357, ICube, Lab Bioinformat Integrat & Genom, Strasbourg, France.
[Sahel, Jose-Alain; Audo, Isabelle] UCL, Inst Ophthalmol, London, England.
[Sahel, Jose-Alain] Fdn Ophtalmol Adolphe Rothschild, Paris, France.
[Sahel, Jose-Alain] Acad Sci Inst France, Paris, France.
RP Zeitz, C (reprint author), INSERM, U968, Paris, France.
EM christina.zeitz@inserm.fr
RI Zeitz, Christina/F-2757-2017; Sahel, Jose-Alain/F-3172-2017;
OI El Shamieh, Said/0000-0002-8522-0445
FU Agence Nationale de la Recherche [ANR-12-BSVS1-0012-01_GPR179];
Foundation Voir et Entendre; Prix Dalloz for "la recherche en
ophtalmologie''; Fondation pour la Recherche Medicale (FRM); Fondation
Roland Bailly; Ville de Paris; Region Ile de France; Agence Nationale de
la Recherche within the Investissements d'Avenir programme
[ANR-11-IDEX-0004-0]; Foundation Fighting Blindness center grant
[C-CMM-0907-0428-INSERM04]
FX The project was supported by Agence Nationale de la Recherche
[ANR-12-BSVS1-0012-01_GPR179] (CZ), Foundation Voir et Entendre (CZ),
Prix Dalloz for "la recherche en ophtalmologie'' (CZ), The Fondation
pour la Recherche Medicale (FRM) in partnership with the Fondation
Roland Bailly (CZ), Ville de Paris and Region Ile de France, LABEX
LIFESENSES [reference ANR-10-LABX-65] supported by French state funds
managed by the Agence Nationale de la Recherche within the
Investissements d'Avenir programme [ANR-11-IDEX-0004-0], Foundation
Fighting Blindness center grant [C-CMM-0907-0428-INSERM04]. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 56
TC 17
Z9 17
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 5
PY 2014
VL 9
IS 3
AR e90342
DI 10.1371/journal.pone.0090342
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC4GP
UT WOS:000332479400065
PM 24598786
ER
PT J
AU Volpp, KG
Galvin, R
AF Volpp, Kevin G.
Galvin, Robert
TI Reward-Based Incentives for Smoking Cessation How a Carrot Became a
Stick
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID FINANCIAL INCENTIVES
C1 [Volpp, Kevin G.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
[Volpp, Kevin G.] Univ Penn, Leonard Davis Inst Hlth Econ, Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA.
[Galvin, Robert] Equ Healthcare, Blackstone Grp, Philadelphia, PA USA.
[Galvin, Robert] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA.
RP Volpp, KG (reprint author), Univ Penn, Perelman Sch Med, Ctr Hlth Incent & Behav Econ, 423 Guardian Dr,1120 Blockley Hall, Philadelphia, PA 19104 USA.
EM volpp70@wharton.upenn.edu
FU NIA NIH HHS [P30 AG034546]
NR 7
TC 13
Z9 13
U1 4
U2 10
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAR 5
PY 2014
VL 311
IS 9
BP 909
EP 910
DI 10.1001/jama.2014.418
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA AC0FS
UT WOS:000332170800015
PM 24493405
ER
PT J
AU Neuhaus, V
Menendez, M
Kurylo, JC
Dyer, GS
Jawa, A
Ring, D
AF Neuhaus, Valentin
Menendez, Mariano
Kurylo, John C.
Dyer, George S.
Jawa, Andrew
Ring, David
TI Risk Factors for Fracture Mobility Six Weeks After Initiation of Brace
Treatment of Mid-Diaphyseal Humeral Fractures
SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME
LA English
DT Article
ID SHAFT FRACTURES; FUNCTIONAL TREATMENT; NONUNION
AB Background: Recent studies have identified specific subsets of diaphyseal humeral fractures for which functional bracing is less effective. The present study tested the hypothesis that a gap between fracture fragments may be a risk factor (after accounting for other potential risk factors) for fracture instability six weeks after functional bracing of humeral shaft fractures.
Methods: We retrospectively identified seventy-nine adult patients (forty-six men, thirty-three women; forty-two fractures on the right side, thirty-seven fractures on the left), each with an acute, closed, AO type-A2 (oblique, >= 30 degrees) or type-A3 (transverse, <30 degrees) mid-diaphyseal humeral shaft fracture treated nonoperatively at three different level-I trauma centers from June 2004 to August 2011. The gap between the fracture fragments was measured on the first radiographs made after the affected upper extremity was placed in a brace.
Results: Sixty-three patients (80%) had documented healing of the fracture. Sixteen patients (20%) had motion at the fracture site and a persistent fracture line shown on radiographs six weeks or more after injury. In multivariable analysis, each millimeter of gap between the main fragments with the patient wearing the brace (odds ratio [OR] = 1.4, 95% confidence interval [CI] = 1.1 to 1.7), smoking (OR = 5.8,95% CI = 1.4 to 25), and female sex (OR = 5.3,95% CI = 1.2 to 23) increased the risk of fracture instability six weeks after injury (R-2 = 0.38, area under the receiver operating characteristic [ROC] curve = 0.81).
Conclusions: The magnitude of the gap between the fracture fragments is an independent risk factor for fracture instability and the lack of a bridging callus six weeks after a diaphyseal humeral fracture.
C1 [Neuhaus, Valentin; Menendez, Mariano; Ring, David] Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Yawkey Ctr, Boston, MA 02114 USA.
[Kurylo, John C.; Jawa, Andrew] Shapiro Ambulatory Care Ctr, Boston Med Ctr, Dept Orthopaed Surg, Boston, MA 02118 USA.
[Dyer, George S.] Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA.
RP Neuhaus, V (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Yawkey Ctr, 55 Fruit St,Suite 2100, Boston, MA 02114 USA.
EM dring@partners.org
OI Neuhaus, Valentin/0000-0003-4012-5628
NR 22
TC 1
Z9 1
U1 0
U2 0
PU JOURNAL BONE JOINT SURGERY INC
PI NEEDHAM
PA 20 PICKERING ST, NEEDHAM, MA 02192 USA
SN 0021-9355
J9 J BONE JOINT SURG AM
JI J. Bone Joint Surg.-Am. Vol.
PD MAR 5
PY 2014
VL 96A
IS 5
BP 403
EP 407
DI 10.2106/JBJS.M.00089
PG 5
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA AC3RY
UT WOS:000332440100008
PM 24599202
ER
PT J
AU Sacks, FM
Hermans, MP
Fioretto, P
Valensi, P
Davis, T
Horton, E
Wanner, C
Al-Rubeaan, K
Aronson, R
Barzon, I
Bishop, L
Bonora, E
Bunnag, P
Chuang, LM
Deerochanawong, C
Goldenberg, R
Harshfield, B
Hernandez, C
Herzlinger-Botein, S
Itoh, H
Jia, WP
Jiang, YD
Kadowaki, T
Laranjo, N
Leiter, L
Miwa, T
Odawara, M
Ohashi, K
Ohno, A
Pan, CY
Pan, J
Pedro-Botet, J
Reiner, Z
Rotella, CM
Simo, R
Tanaka, M
Tedeschi-Reiner, E
Twum-Barima, D
Zoppini, G
Carey, VJ
AF Sacks, Frank M.
Hermans, Michel P.
Fioretto, Paola
Valensi, Paul
Davis, Timothy
Horton, Edward
Wanner, Christoph
Al-Rubeaan, Khalid
Aronson, Ronnie
Barzon, Isabella
Bishop, Louise
Bonora, Enzo
Bunnag, Pongamorn
Chuang, Lee-Ming
Deerochanawong, Chaicharn
Goldenberg, Ronald
Harshfield, Benjamin
Hernandez, Cristina
Herzlinger-Botein, Susan
Itoh, Hiroshi
Jia, Weiping
Jiang, Yi-Der
Kadowaki, Takashi
Laranjo, Nancy
Leiter, Lawrence
Miwa, Takashi
Odawara, Masato
Ohashi, Ken
Ohno, Atsushi
Pan, Changyu
Pan, Jiemin
Pedro-Botet, Juan
Reiner, Zeljko
Rotella, Carlo Maria
Simo, Rafael
Tanaka, Masami
Tedeschi-Reiner, Eugenia
Twum-Barima, David
Zoppini, Giacomo
Carey, Vincent J.
TI Association Between Plasma Triglycerides and High-Density Lipoprotein
Cholesterol and Microvascular Kidney Disease and Retinopathy in Type 2
Diabetes Mellitus A Global Case-Control Study in 13 Countries
SO CIRCULATION
LA English
DT Article
DE diabetes mellitus; diabetic retinopathy; epidemiology; kidney; lipids;
risk factors
ID INDEPENDENT RISK-FACTOR; CARDIOVASCULAR-DISEASE; MACULAR EDEMA;
SERUM-LIPIDS; ATHEROSCLEROSIS RISK; APOLIPOPROTEIN-CIII; RENAL
DYSFUNCTION; HARD EXUDATE; PROGRESSION; HYPERTRIGLYCERIDEMIA
AB Background Microvascular renal and retinal diseases are common major complications of type 2 diabetes mellitus. The relation between plasma lipids and microvascular disease is not well established.
Methods and Results The case subjects were 2535 patients with type 2 diabetes mellitus with an average duration of 14 years, 1891 of whom had kidney disease and 1218 with retinopathy. The case subjects were matched for diabetes mellitus duration, age, sex, and low-density lipoprotein cholesterol to 3683 control subjects with type 2 diabetes mellitus who did not have kidney disease or retinopathy. The study was conducted in 24 sites in 13 countries. The primary analysis included kidney disease and retinopathy cases. Matched analysis was performed by use of site-specific conditional logistic regression in multivariable models that adjusted for hemoglobin A(1c), hypertension, and statin treatment. Mean low-density lipoprotein cholesterol concentration was 2.3 mmol/L. The microvascular disease odds ratio increased by a factor of 1.16 (95% confidence interval, 1.11-1.22) for every 0.5 mmol/L (approximate to 1 quintile) increase in triglycerides or decreased by a factor of 0.92 (0.88-0.96) for every 0.2 mmol/L (approximate to 1 quintile) increase in high-density lipoprotein cholesterol. For kidney disease, the odds ratio increased by 1.23 (1.16-1.31) with triglycerides and decreased by 0.86 (0.82-0.91) with high-density lipoprotein cholesterol. Retinopathy was associated with triglycerides and high-density lipoprotein cholesterol in matched analysis but not significantly after additional adjustment.
Conclusions Diabetic kidney disease is associated worldwide with higher levels of plasma triglycerides and lower levels of high-density lipoprotein cholesterol among patients with good control of low-density lipoprotein cholesterol. Retinopathy was less robustly associated with these lipids. These results strengthen the rationale for studying dyslipidemia treatment to prevent diabetic microvascular disease.
C1 [Sacks, Frank M.; Bishop, Louise] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Hermans, Michel P.] Catholic Univ Louvain, Clin Univ St Luc, B-1200 Brussels, Belgium.
[Fioretto, Paola; Barzon, Isabella] Univ Padua, Dept Med, Padua, Italy.
[Valensi, Paul] Univ Paris Nord, Ctr Rech Nutr Humaine Ille France, Jean Verdier Hosp, Dept Endocrinol Diabetol Nutr,AP HP, Bondy, France.
[Davis, Timothy] Univ Western Australia, Crawley, Australia.
[Horton, Edward; Herzlinger-Botein, Susan] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA.
[Wanner, Christoph] Univ Wurzburg, D-97070 Wurzburg, Germany.
[Al-Rubeaan, Khalid] King Saud Univ, Coll Med, Riyadh 11461, Saudi Arabia.
[Aronson, Ronnie] LMC Diabet & Endocrinol, Toronto, ON, Canada.
[Bonora, Enzo; Zoppini, Giacomo] Univ Verona, Dept Med, Endocrinol Sect, I-37100 Verona, Italy.
[Bunnag, Pongamorn] Ramathibodi Hosp, Bangkok, Thailand.
[Chuang, Lee-Ming; Jiang, Yi-Der] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan.
[Deerochanawong, Chaicharn] Rajavithi Hosp, Rangsit Sch Med, Bangkok, Thailand.
[Goldenberg, Ronald] North York Gen Hosp, Toronto, ON, Canada.
[Goldenberg, Ronald] LMC Diabet Ctr, Toronto, ON, Canada.
[Goldenberg, Ronald] Endocrinol Ctr, Toronto, ON, Canada.
[Harshfield, Benjamin; Laranjo, Nancy; Carey, Vincent J.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Hernandez, Cristina; Simo, Rafael] CIBERDEM, Barcelona, Spain.
[Hernandez, Cristina; Simo, Rafael] Vall dHebron Res Inst, Barcelona, Spain.
[Itoh, Hiroshi; Tanaka, Masami] Keio Univ, Sch Med, Tokyo, Japan.
[Jia, Weiping] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Shanghai Diabet Inst, Shanghai Clin Ctr Diabet, Shanghai 200030, Peoples R China.
[Kadowaki, Takashi] Univ Tokyo, Dept Diabet & Metab Dis, Tokyo, Japan.
[Leiter, Lawrence] Univ Toronto, Toronto, ON, Canada.
[Miwa, Takashi; Odawara, Masato] Tokyo Med Univ, Tokyo 1608402, Japan.
[Ohashi, Ken] Natl Canc Ctr, Dept Gen Internal Med, Tokyo, Japan.
[Ohno, Atsushi] Tokyo Med Univ, Hachioji Med Ctr, Tokyo 1608402, Japan.
[Pan, Changyu] Beijing 301 Mil Hosp, Beijing, Peoples R China.
[Pan, Jiemin] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Endocrinol & Metab, Shanghai 200030, Peoples R China.
[Pedro-Botet, Juan] Univ Autonoma Barcelona, Hosp del Mar, E-08193 Barcelona, Spain.
[Reiner, Zeljko] Univ Zagreb, Univ Hosp Ctr Zagreb Sch Med, Dept Internal Med, Zagreb 41000, Croatia.
[Rotella, Carlo Maria] Univ Florence, Dept Clin Pathophysiol, Endocrinol Sect, Florence, Italy.
[Tedeschi-Reiner, Eugenia] Univ Hosp Sestre Milosrdnice, Dept Ophthalmol, Zagreb, Croatia.
[Twum-Barima, David] LMC Diabet & Endocrinol, Oakville, ON, Canada.
RP Sacks, FM (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA.
EM fsacks@hsph.harvard.edu
RI Davis, Timothy/M-5144-2014; Fernandez , Irene/E-5705-2016;
OI Rotella, Carlo Maria/0000-0001-9462-2334; BONORA,
Enzo/0000-0003-1074-5164; CHUANG, LEE-MING/0000-0003-0978-2662; Simo
Canonge, Rafael/0000-0003-0475-3096
FU R3i (Residual Risk Reduction Institute) Foundation grant
FX This study was funded by an R3i (Residual Risk Reduction Institute)
Foundation grant to Brigham and Women's Hospital and Harvard School of
Public Health and to the individual study sites. The sponsor provided
logistical support to the sites and the coordinating center.
NR 50
TC 44
Z9 48
U1 0
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAR 4
PY 2014
VL 129
IS 9
BP 999
EP 1008
DI 10.1161/CIRCULATIONAHA.113.002529
PG 10
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AB9UF
UT WOS:000332140500012
PM 24352521
ER
PT J
AU Corato, M
De Nittis, P
Trenti, N
Paganoni, S
AF Corato, Manuel
De Nittis, Pasquale
Trenti, Nicoletta
Paganoni, Sabrina
TI Teaching NeuroImages: Median nerve MRI changes over time in neuralgic
amyotrophy
SO NEUROLOGY
LA English
DT Editorial Material
AB A 40-year-old woman presented with 2 weeks of left arm pain followed by hand weakness and numbness. Electrodiagnostic testing revealed an isolated median sensorimotor axonopathy localizing proximal to the pronator teres. The working diagnosis of a forme fruste of neuralgic amyotrophy was made. MRI of the left arm was performed to exclude rare structural causes of proximal median neuropathy. The median nerve showed inflammatory features with a diffusely increased signal on short tau inversion recovery sequences that enhanced with gadolinium (figure, A). Two years after onset, symptoms had resolved. Repeat MRI showed resolution of the abnormal findings (figure, B).
C1 [Corato, Manuel] Ist Clin Humanitas IRCCS, Emergency Neurol & Stroke Unit, Rozzano, Italy.
[De Nittis, Pasquale] Ist Clin Humanitas IRCCS, Ultrasound Unit, Dept Diagnost Imaging, Rozzano, Italy.
[Trenti, Nicoletta] Ist Clin Humanitas IRCCS, Dept Radiol, Rozzano, Italy.
[Paganoni, Sabrina] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Paganoni, Sabrina] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA.
[Paganoni, Sabrina] VA Boston Healthcare Syst, Boston, MA USA.
RP Paganoni, S (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
EM spaganoni@partners.org
NR 0
TC 2
Z9 2
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD MAR 4
PY 2014
VL 82
IS 9
BP E79
EP E79
DI 10.1212/WNL.0000000000000171
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA AG9OD
UT WOS:000335748100003
PM 24590253
ER
PT J
AU de Luca, A
Smeekens, SP
Casagrande, A
Iannitti, R
Conway, KL
Gresnigt, MS
Begun, J
Plantinga, TS
Joosten, LAB
van der Meer, JWM
Chamilos, G
Netea, MG
Xavier, RJ
Dinarello, CA
Romani, L
van de Veerdonk, FL
AF de Luca, Antonella
Smeekens, Sanne P.
Casagrande, Andrea
Iannitti, Rossana
Conway, Kara L.
Gresnigt, Mark. S.
Begun, Jakob
Plantinga, Theo S.
Joosten, Leo A. B.
van der Meer, Jos W. M.
Chamilos, Georgios
Netea, Mihai G.
Xavier, Ramnik J.
Dinarello, Charles A.
Romani, Luigina
van de Veerdonk, Frank L.
TI IL-1 receptor blockade restores autophagy and reduces inflammation in
chronic granulomatous disease in mice and in humans
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE interleukin-1; S. aureus; LPS; Crohn disease; autoinflammatory disease
ID CROHNS-DISEASE; IL-1-BETA PRODUCTION; NADPH OXIDASES; ACTIVATION;
COLITIS; CELLS; INTERLEUKIN-1-BETA; SUSCEPTIBILITY; COMPLICATIONS;
DYSFUNCTION
AB Patients with chronic granulomatous disease (CGD) have a mutated NADPH complex resulting in defective production of reactive oxygen species; these patients can develop severe colitis and are highly susceptible to invasive fungal infection. In NADPH oxidase-deficient mice, autophagy is defective but inflammasome activation is present despite lack of reactive oxygen species production. However, whether these processes are mutually regulated in CGD and whether defective autophagy is clinically relevant in patients with CGD is unknown. Here, we demonstrate that macrophages from CGD mice and blood monocytes from CGD patients display minimal recruitment of microtubule-associated protein 1 light chain 3 (LC3) to phagosomes. This defect in autophagy results in increased IL-1 beta release. Blocking IL-1 with the receptor antagonist (anakinra) decreases neutrophil recruitment and T helper 17 responses and protects CGD mice from colitis and also from invasive aspergillosis. In addition to decreased inflammasome activation, anakinra restored autophagy in CGD mice in vivo, with increased Aspergillus-induced LC3 recruitment and increased expression of autophagy genes. Anakinra also increased Aspergillus-induced LC3 recruitment from 23% to 51% (P < 0.01) in vitro in monocytes from CGD patients. The clinical relevance of these findings was assessed by treating CGD patients who had severe colitis with IL-1 receptor blockade using anakinra. Anakinra treatment resulted in a rapid and sustained improvement in colitis. Thus, inflammation in CGD is due to IL-1-dependent mechanisms, such as decreased autophagy and increased inflammasome activation, which are linked pathological conditions in CGD that can be restored by IL-1 receptor blockade.
C1 [de Luca, Antonella; Casagrande, Andrea; Iannitti, Rossana; Romani, Luigina] Univ Perugia, Dept Expt Med & Biochem Sci, I-06122 Perugia, Italy.
[Smeekens, Sanne P.; Gresnigt, Mark. S.; Plantinga, Theo S.; Joosten, Leo A. B.; van der Meer, Jos W. M.; Netea, Mihai G.; Dinarello, Charles A.; van de Veerdonk, Frank L.] Radboud Univ Nijmegen, Med Ctr, Dept Med, NL-6500 HB Nijmegen, Netherlands.
[Smeekens, Sanne P.; Gresnigt, Mark. S.; Plantinga, Theo S.; Joosten, Leo A. B.; van der Meer, Jos W. M.; Netea, Mihai G.; Dinarello, Charles A.; van de Veerdonk, Frank L.] Nijmegen Inst Infect Inflammat & Immun, NL-6500 HB Nijmegen, Netherlands.
[Conway, Kara L.; Begun, Jakob; Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
[Conway, Kara L.; Begun, Jakob; Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Chamilos, Georgios] Univ Crete, Dept Internal Med, Iraklion 71003, Crete, Greece.
[Chamilos, Georgios] Fdn Res & Technol, Inst Mol Biol & Biotechnol, Iraklion 71003, Crete, Greece.
[Xavier, Ramnik J.; Dinarello, Charles A.] Univ Colorado Denver, Div Infect Dis, Aurora, CO 80045 USA.
[van de Veerdonk, Frank L.] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA 02142 USA.
RP Dinarello, CA (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Med, NL-6500 HB Nijmegen, Netherlands.
EM cdinarello@mac.com; f.veerdonk@aig.umcn.nl
RI Smeekens, Sanne/G-8307-2011; Begun, Jakob/J-6793-2014; Plantinga,
Theo/A-6895-2015; Joosten, Leo/H-3138-2015; Gresnigt, Mark/H-3530-2015;
van de Veerdonk, Frank/C-7256-2008; Netea, Mihai/N-5155-2014; van der
Meer, Jos/C-8521-2013;
OI Romani, Luigina/0000-0002-1356-525X; Smeekens,
Sanne/0000-0002-7835-914X; Begun, Jakob/0000-0001-5256-7672; Gresnigt,
Mark/0000-0002-9514-4634; van de Veerdonk, Frank/0000-0002-1121-4894;
van der Meer, Jos/0000-0001-5120-3690; DE LUCA,
ANTONELLA/0000-0002-6866-5530
FU Veni grant of the Netherlands Organization for Scientific Research; Vici
grant; European Union's Seventh Framework Programme
[ERC-2011-AdG-293714]; National Institutes of Health (NIH) [DK-83756,
AI-62773, DK-60049, DK-43351, AI-15614]
FX This study was supported by a Veni grant of the Netherlands Organization
for Scientific Research (to F.L.v.d.V.) and a Vici grant (to M.G.N.). It
was also supported by the European Union's Seventh Framework Programme
Agreement ERC-2011-AdG-293714 [metabolomics of fungal diseases: a
systems biology approach for biomarkers discovery and therapy (FUNMETA)]
(to L. R.) and by National Institutes of Health (NIH) Grants DK-83756,
AI-62773, DK-60049, and DK-43351 (to R.J.X.) and NIH Grant AI-15614 (to
C.A.D.).
NR 45
TC 62
Z9 62
U1 0
U2 17
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD MAR 4
PY 2014
VL 111
IS 9
BP 3526
EP 3531
DI 10.1073/pnas.1322831111
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AC5KR
UT WOS:000332560300074
PM 24550444
ER
PT J
AU Rittling, SR
Wejse, PL
Yagiz, K
Warot, GA
Hui, T
AF Rittling, S. R.
Wejse, P. L.
Yagiz, K.
Warot, G. A.
Hui, T.
TI Suppression of tumour growth by orally administered osteopontin is
accompanied by alterations in tumour blood vessels
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
ID ENZYME-INHIBITORY PEPTIDES; IN-VITRO; INTEGRIN ALPHA-9-BETA-1; MICE
LACKING; HUMAN-MILK; ANGIOGENESIS; CILENGITIDE; CANCER; CELLS;
GLIOBLASTOMA
AB Background: The integrin-binding protein osteopontin is strongly associated with tumour development, yet is an abundant dietary component as a constituent of human and bovine milk. Therefore, we tested the effect of orally administered osteopontin (o-OPN) on the development of subcutaneous tumours in mice.
Methods: Bovine milk osteopontin was administered in drinking water to tumour-bearing immune-competent mice. Tumour growth, proliferation, necrosis, apoptosis and blood vessel size and number were measured. Expression of the alpha(9) integrin was determined.
Results: o-OPN suppressed tumour growth, increased the extent of necrosis, and induced formation of abnormally large blood vessels. Anti-OPN reactivity detected in the plasma of OPN-null mice fed OPN suggested that tumour-blocking peptides were absorbed during digestion, but the o-OPN effect was likely distinct from that of an RGD peptide. Expression of the alpha(9) integrin was detected on both tumour cells and blood vessels. Potential active peptides from the alpha(9) binding site of OPN were identified by mass spectrometry following in vitro digestion, and injection of these peptides suppressed tumour growth.
Conclusions: These results suggest that peptides derived from o-OPN are absorbed and interfere with tumour growth and normal vessel development. o-OPN-derived peptides that target the alpha(9) integrin are likely involved.
C1 [Rittling, S. R.; Yagiz, K.; Warot, G. A.; Hui, T.] Forsyth Inst, Cambridge, MA 02412 USA.
[Wejse, P. L.] Arla Foods Ingredients Grp PS, DK-8260 Viby J, Denmark.
RP Rittling, SR (reprint author), Forsyth Inst, 245 First St, Cambridge, MA 02412 USA.
EM srittling@forsyth.org
FU Arla Foods Ingredients
FX We thank Esben Sorensen for the gift of anti-OPN antibodies, Toshimitsu
Uede for the gift of the alpha9 antibody and Simon Goodman
for critical reading of the manuscript. The Cilengitide was generously
provided by Merck KgaA and the CTEP, National Cancer Institute, NIH. We
appreciate technical assistance by Hannah McLeod, Eva Xia and Carolina
Brettler. This work was supported by grants from Arla Foods Ingredients.
NR 51
TC 3
Z9 3
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
EI 1532-1827
J9 BRIT J CANCER
JI Br. J. Cancer
PD MAR 4
PY 2014
VL 110
IS 5
BP 1269
EP 1277
DI 10.1038/bjc.2014.10
PG 9
WC Oncology
SC Oncology
GA AC9EB
UT WOS:000332836000021
PM 24473400
ER
PT J
AU de Koning, HJ
Meza, R
Plevritis, SK
ten Haaf, K
Munshi, VN
Jeon, J
Erdogan, SA
Kong, CY
Han, SS
van Rosmalen, J
Choi, SE
Pinsky, PF
de Gonzalez, AB
Berg, CD
Black, WC
Tammemagi, MC
Hazelton, WD
Feuer, EJ
McMahon, PM
AF de Koning, Harry J.
Meza, Rafael
Plevritis, Sylvia K.
ten Haaf, Kevin
Munshi, Vidit N.
Jeon, Jihyoun
Erdogan, Saadet Ayca
Kong, Chung Yin
Han, Summer S.
van Rosmalen, Joost
Choi, Sung Eun
Pinsky, Paul F.
de Gonzalez, Amy Berrington
Berg, Christine D.
Black, William C.
Tammemaegi, Martin C.
Hazelton, William D.
Feuer, Eric J.
McMahon, Pamela M.
TI Benefits and Harms of Computed Tomography Lung Cancer Screening
Strategies: A Comparative Modeling Study for the US Preventive Services
Task Force
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID LOW-DOSE CT; UNITED-STATES; SMOKING ABSTINENCE; SELECTION CRITERIA;
NELSON TRIAL; POPULATION; MORTALITY; PROSTATE; STAGE; RISK
AB Background: The optimum screening policy for lung cancer is unknown.
Objective: To identify efficient computed tomography (CT) screening scenarios in which relatively more lung cancer deaths are averted for fewer CT screening examinations.
Design: Comparative modeling study using 5 independent models.
Data Sources: The National Lung Screening Trial; the Prostate, Lung, Colorectal, and Ovarian Cancer Screening trial; the Surveillance, Epidemiology, and End Results program; and the U.S. Smoking History Generator.
Target Population: U.S. cohort born in 1950.
Time Horizon: Cohort followed from ages 45 to 90 years.
Perspective: Societal.
Intervention: 576 scenarios with varying eligibility criteria (age, pack-years of smoking, years since quitting) and screening intervals.
Outcome Measures: Benefits included lung cancer deaths averted or life-years gained. Harms included CT examinations, false-positive results (including those obtained from biopsy/surgery), overdiagnosed cases, and radiation-related deaths.
Results of Best-Case Scenario: The most advantageous strategy was annual screening from ages 55 through 80 years for ever-smokers with a smoking history of at least 30 pack-years and ex-smokers with less than 15 years since quitting. It would lead to 50% (model ranges, 45% to 54%) of cases of cancer being detected at an early stage (stage I/II), 575 screening examinations per lung cancer death averted, a 14% (range, 8.2% to 23.5%) reduction in lung cancer mortality, 497 lung cancer deaths averted, and 5250 life-years gained per the 100 000-member cohort. Harms would include 67 550 false-positive test results, 910 biopsies or surgeries for benign lesions, and 190 overdiagnosed cases of cancer (3.7% of all cases of lung cancer [model ranges, 1.4% to 8.3%]).
Results of Sensitivity Analysis: The number of cancer deaths averted for the scenario varied across models between 177 and 862; the number of overdiagnosed cases of cancer varied between 72 and 426.
Limitations: Scenarios assumed 100% screening adherence. Data derived from trials with short duration were extrapolated to lifetime follow-up.
Conclusion: Annual CT screening for lung cancer has a favorable benefit-harm ratio for individuals aged 55 through 80 years with 30 or more pack-years' exposure to smoking.
C1 Erasmus MC, NL-3000 CA Rotterdam, Netherlands.
Univ Michigan, Ann Arbor, MI 48109 USA.
Stanford Univ, Stanford, CA 94305 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
NCI, Bethesda, MD 20892 USA.
Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA.
Brock Univ, St Catharines, ON L2S 3A1, Canada.
RP de Koning, HJ (reprint author), Erasmus MC, Dept Publ Hlth, POB 2040, NL-3000 CA Rotterdam, Netherlands.
EM h.dekoning@erasmusmc.nl
RI Berg , Christine/K-1047-2014
FU National Cancer Institute
FX Primary Funding Source: National Cancer Institute.
NR 42
TC 120
Z9 121
U1 6
U2 23
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD MAR 4
PY 2014
VL 160
IS 5
BP 311
EP +
DI 10.7326/M13-2316
PG 15
WC Medicine, General & Internal
SC General & Internal Medicine
GA AC8OT
UT WOS:000332793900003
PM 24379002
ER
PT J
AU Downs, J
Good, C
AF Downs, John
Good, Chester
TI New Cholesterol Guidelines: Has Godot Finally Arrived?
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Editorial Material
C1 South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
Univ Pittsburgh, Pittsburgh, PA USA.
RP Downs, J (reprint author), South Texas Vet Hlth Care Syst, Med Serv 111, 7400 Merton Minter, San Antonio, TX 78229 USA.
EM john.downs@va.gov
NR 9
TC 8
Z9 8
U1 0
U2 1
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD MAR 4
PY 2014
VL 160
IS 5
BP 354
EP +
DI 10.7326/M13-2850
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA AC8OT
UT WOS:000332793900008
PM 24473934
ER
PT J
AU Capasso, R
Kezirian, E
Jacobowitz, O
Weaver, EM
AF Capasso, Robson
Kezirian, Eric
Jacobowitz, Ofer
Weaver, Edward M.
TI Management of Obstructive Sleep Apnea in Adults
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Letter
ID POSITIVE AIRWAY PRESSURE
C1 [Capasso, Robson] Stanford Univ, Palo Alto, CA 94304 USA.
[Kezirian, Eric] Univ So Calif, Los Angeles, CA USA.
[Jacobowitz, Ofer] Mt Sinai Sch Med, New York, NY USA.
[Weaver, Edward M.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA.
RP Capasso, R (reprint author), Stanford Univ, Palo Alto, CA 94304 USA.
NR 5
TC 1
Z9 2
U1 0
U2 2
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD MAR 4
PY 2014
VL 160
IS 5
BP 367
EP 367
DI 10.7326/L14-5005
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA AC8OT
UT WOS:000332793900014
PM 24589933
ER
PT J
AU Shekelle, P
Holty, JEC
Owens, DK
Qaseem, A
AF Shekelle, Paul
Holty, Jon-Erik C.
Owens, Douglas K.
Qaseem, Amir
TI Management of Obstructive Sleep Apnea in Adults IN RESPONSE
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Letter
ID TRIAL
C1 [Shekelle, Paul] Greater Los Angeles Vet Affairs Hlth Ctr, Los Angeles, CA 90073 USA.
[Shekelle, Paul] RAND Corp, Los Angeles, CA USA.
[Holty, Jon-Erik C.; Owens, Douglas K.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA.
[Qaseem, Amir] Amer Coll Physicians, Philadelphia, PA USA.
RP Shekelle, P (reprint author), Greater Los Angeles Vet Affairs Hlth Ctr, Los Angeles, CA 90073 USA.
NR 4
TC 2
Z9 4
U1 0
U2 0
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD MAR 4
PY 2014
VL 160
IS 5
BP 367
EP 368
DI 10.7326/L14-5005-2
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA AC8OT
UT WOS:000332793900015
PM 24737275
ER
PT J
AU Wright, AA
Zhang, BH
Keating, NL
Weeks, JC
Prigerson, HG
AF Wright, Alexi A.
Zhang, Baohui
Keating, Nancy L.
Weeks, Jane C.
Prigerson, Holly G.
TI Associations between palliative chemotherapy and adult cancer patients'
end of life care and place of death: prospective cohort study
SO BMJ-BRITISH MEDICAL JOURNAL
LA English
DT Article
ID CELL LUNG-CANCER; OF-LIFE; MEDICARE BENEFICIARIES; TREATMENT
PREFERENCES; PROPENSITY SCORE; MENTAL-HEALTH; HOSPICE CARE; NEAR-DEATH;
DISCUSSIONS; QUALITY
AB Objectives To determine whether the receipt of chemotherapy among terminally ill cancer patients months before death was associated with patients' subsequent intensive medical care and place of death.
Design Secondary analysis of a prospective, multi-institution, longitudinal study of patients with advanced cancer.
Setting Eight outpatient oncology clinics in the United States.
Participants 386 adult patients with metastatic cancers refractory to at least one chemotherapy regimen, whom physicians identified as terminally ill at study enrollment and who subsequently died.
Main outcome measures Primary outcomes: intensive medical care (cardiopulmonary resuscitation, mechanical ventilation, or both) in the last week of life and patients' place of death (for example, intensive care unit). Secondary outcomes: survival, late hospice referrals (<= 1 week before death), and dying in preferred place of death.
Results 216 (56%) of 386 terminally ill cancer patients were receiving palliative chemotherapy at study enrollment, a median of 4.0 months before death. After propensity score weighted adjustment, use of chemotherapy at enrollment was associated with higher rates of cardiopulmonary resuscitation, mechanical ventilation, or both in the last week of life (14% v 2%; adjusted risk difference 10.5%, 95% confidence interval 5.0% to 15.5%) and late hospice referrals (54% v 37%; 13.6%, 3.6% to 23.6%) but no difference in survival (hazard ratio 1.11, 95% confidence interval 0.90 to 1.38). Patients receiving palliative chemotherapy were more likely to die in an intensive care unit (11% v 2%; adjusted risk difference 6.1%, 1.1% to 11.1%) and less likely to die at home (47% v 66%; -10.8%, -1.0% to -20.6%), compared with those who were not. Patients receiving palliative chemotherapy were also less likely to die in their preferred place, compared with those who were not (65% v 80%; adjusted risk difference -9.4%, -0.8% to -18.1%).
Conclusions The use of chemotherapy in terminally ill cancer patients in the last months of life was associated with an increased risk of undergoing cardiopulmonary resuscitation, mechanical ventilation or both and of dying in an intensive care unit. Future research should determine the mechanisms by which palliative chemotherapy affects end of life outcomes and patients' attainment of their goals.
C1 [Wright, Alexi A.; Weeks, Jane C.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA.
[Zhang, Baohui; Prigerson, Holly G.] Weill Cornell Med Coll, Ctr End Of Life Res, New York, NY 10065 USA.
[Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
RP Prigerson, HG (reprint author), Weill Cornell Med Coll, Ctr End Of Life Res, New York, NY 10065 USA.
EM hgp2001@med.cornell.edu
FU National Institute of Mental Health [MH63892]; National Cancer Institute
[CA 106370, CA 156732, 1K07 CA166210, 1R01 CA164021]; American Cancer
Society [MRSG-13-013]; Conquer Cancer Foundation of American Society for
Clinical Oncology Career Development Award
FX HGP has received research grants MH63892 from the National Institute of
Mental Health and CA 106370 and CA 156732 from the National Cancer
Institute; AAW has received research grants 1K07 CA166210 from the
National Cancer Institute and MRSG-13-013 from the American Cancer
Society and a Conquer Cancer Foundation of American Society for Clinical
Oncology Career Development Award; NLK received research grant 1R01
CA164021 from the National Cancer Institute. The funding organizations
had no role in the design and conduct of the study; collection,
analysis, or preparation of the data; or preparation, review, or
approval of the manuscript. Any opinions, findings, and conclusions
expressed in this material are those of the authors and do not
necessarily reflect those of the American Cancer Society, the American
Society of Clinical Oncology, or the Conquer Cancer Foundation.
NR 48
TC 49
Z9 49
U1 7
U2 28
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1756-1833
J9 BMJ-BRIT MED J
JI BMJ-British Medical Journal
PD MAR 4
PY 2014
VL 348
AR g1219
DI 10.1136/bmj.g1219
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA AC6HV
UT WOS:000332623400001
PM 24594868
ER
PT J
AU Ferreiro, JL
Bhatt, DL
Ueno, M
Bauer, D
Angiolillo, DJ
AF Ferreiro, Jose L.
Bhatt, Deepak L.
Ueno, Masafumi
Bauer, Deborah
Angiolillo, Dominick J.
TI Impact of Smoking on Long-Term Outcomes in Patients With Atherosclerotic
Vascular Disease Treated With Aspirin or Clopidogrel
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE antiplatelet agents; clopidogrel; smoking; smoking paradox
ID ACUTE CORONARY SYNDROMES; CIGARETTE-SMOKING; PLATELET INHIBITION;
ARTERY-DISEASE; DIABETES-MELLITUS; DRUG-INTERACTIONS; ISCHEMIC EVENTS;
EFFICACY; PRASUGREL; PARADOX
AB Objectives The goal of this study was to investigate the differential efficacy of clopidogrel or aspirin monotherapy according to smoking status in patients with atherosclerotic vascular disease.
Background Smoking enhances clopidogrel- induced platelet inhibition, which may explain the higher relative benefit among smokers observed in trials evaluating dual antiplatelet therapy. Whether smoking has an impact on clinical outcomes in patients requiring a single antiplatelet agent remains unknown.
Methods This was a post- hoc analysis of the CAPRIE (Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events) trial that compared clopidogrel and aspirin monotherapy in patients (N = 19,184) with atherosclerotic vascular disease.
Results Current smokers (n = 5,688) had an increased risk of ischemic events compared with never smokers (n = 4,135; hazard ratio [HR]: 1.24 [95% confidence interval (CI): 1.08 to 1.42]) and ex- smokers (n = 9,381; HR: 1.32 [95% CI: 1.18 to 1.47]) (p< 0.001). Clopidogrel was associated with a reduction in ischemic events among current smokers (8.3% vs. 10.8%; HR: 0.76 [95% CI: 0.64 to 0.90]), whereas no benefit over aspirin was seen in the combined group of ex- smokers/never- smoked patients (10.4% vs. 10.6%; HR: 0.99 [95% CI: 0.89 to 1.10]; p = 0.01 for interaction). Among current smokers, clopidogrel also reduced myocardial infarction, vascular death, and death from any cause compared with aspirin. No interaction between smoking status and study treatment was observed for bleeding events.
Conclusions In a post-hoc analysis of the CAPRIE population, current smokers appeared to have enhanced benefit with clopidogrel therapy for secondary prevention compared with aspirin. These results should be considered hypothesis generating for future prospective studies assessing the impact of specific platelet- inhibiting strategies according to smoking status. (c) 2014 by the American College of Cardiology Foundation
C1 [Ferreiro, Jose L.; Ueno, Masafumi; Angiolillo, Dominick J.] Univ Florida Coll Med Jacksonville, Jacksonville, FL 32209 USA.
[Ferreiro, Jose L.] Univ Barcelona, Hosp Univ Bellvitge IDIBELL, Heart Dis Inst, Barcelona, Spain.
[Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA.
[Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA.
[Bauer, Deborah] Sanofi, Dept Biostat, Bridgewater, NJ USA.
RP Angiolillo, DJ (reprint author), Univ Florida Coll Med Jacksonville, 655 West 8th St, Jacksonville, FL 32209 USA.
EM dominick.angiolillo@jax.ufl.edu
FU Sanofi; Bristol-Myers Squibb; Amarin; AstraZeneca; Eisai; Ethicon;
Medtronic; sanofi-aventis; Medicines Company; Eli Lilly and Company;
Daiichi Sankyo; Merck Co.; Evolva; Abbott Vascular; PLx Pharma;
GlaxoSmithKline; Otsuka; Esther and King Biomedical Research Grant
FX The CAPRIE trial was funded by Sanofi and Bristol-Myers Squibb. The
study sponsor had no role in the design of the present analysis. Dr.
Ferreiro has received honoraria for lectures from Eli Lilly and Company,
Daiichi Sankyo, and AstraZeneca. Dr. Bhatt has been on the advisory
boards of Elsevier Practice Update Cardiology, Medscape Cardiology, and
Regado Biosciences; has been on the board of directors of Boston VA
Research Institute and the Society of Chest Pain Centers; has chaired
the American Heart Association Get With the Guidelines Science
Subcommittee; has received honoraria from the American College of
Cardiology, Duke Clinical Research Institute, Slack Publications, and
WebMD; has been a senior associate editor of the Journal of Invasive
Cardiology; has been on data monitoring committees of Duke Clinical
Research Institute, Mayo Clinic, and Population Health Research
Institute; has received research grants from Amarin, AstraZeneca,
Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, sanofi-aventis, and The
Medicines Company; has performed unfunded research for FlowCo, PLx
Pharma, and Takeda; has been a principal investigator on the CHARISMA
trial; has been on the steering committee of the TRILOGY-ACS trial; and
has been on the executive committee of the PEGASUS trial(s). Ms. Bauer
is an employee of sanofi-aventis. Dr. Angiolillo has received consulting
fees or honoraria from Bristol-Myers Squibb, sanofi-aventis, Eli Lilly
and Company, Daiichi Sankyo, The Medicines Company, AstraZeneca, Merck &
Co., Evolva, Abbott Vascular, and PLx Pharma; has been a consultant for
Johnson & Johnson, St. Jude Medical, and Sunovion; has received research
grants (paid to his institution) from Bristol-Myers Squibb,
sanofi-aventis, GlaxoSmithKline, Otsuka, Eli Lilly and Company, Daiichi
Sankyo, The Medicines Company, AstraZeneca, and Evolva; and has received
an Esther and King Biomedical Research Grant. Dr. Ueno has reported that
he has no relationships relevant to the contents of this paper to
disclose.
NR 39
TC 13
Z9 15
U1 1
U2 15
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 4
PY 2014
VL 63
IS 8
BP 769
EP 777
DI 10.1016/j.jacc.2013.10.043
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AB3WM
UT WOS:000331720900004
PM 24239662
ER
PT J
AU Shah, R
Gayat, E
Januzzi, JL
Sato, N
Cohen-Solal, A
diSomma, S
Fairman, E
Harjola, VP
Ishihara, S
Lassus, J
Maggioni, A
Metra, M
Mueller, C
Mueller, T
Parenica, J
Pascual-Figal, D
Peacock, WF
Spinar, J
van Kimmenade, R
Mebazaa, A
AF Shah, Ravi
Gayat, Etienne
Januzzi, James L., Jr.
Sato, Naoki
Cohen-Solal, Alain
diSomma, Salvatore
Fairman, Enrique
Harjola, Veli-Pekka
Ishihara, Shiro
Lassus, Johan
Maggioni, Aldo
Metra, Marco
Mueller, Christian
Mueller, Thomas
Parenica, Jiri
Pascual-Figal, Domingo
Peacock, William Frank
Spinar, Jindrich
van Kimmenade, Roland
Mebazaa, Alexandre
CA GREAT Global Res Acute Conditions
TI Body Mass Index and Mortality in Acutely Decompensated Heart Failure
Across the World
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE heart failure; obesity; obesity paradox
ID OBESITY PARADOX; NATRIURETIC PEPTIDE; CARDIAC CACHEXIA; PREDICTORS;
DIAGNOSIS; REGISTRY; CATABOLISM; ADIPOSITY; REDUCTION; PROGNOSIS
AB Objectives This study sought to define the relationship between body mass index (BMI) and mortality in heart failure (HF) across the world and to identify specific groups in whom BMI may differentially mediate risk.
Background Obesity is associated with incident HF, but it is paradoxically associated with better prognosis during chronic HF.
Methods We studied 6,142 patients with acute decompensated HF from 12 prospective observational cohorts followed-up across 4 continents. Primary outcome was all-cause mortality. Cox proportional hazards models and net reclassification index described associations of BMI with all-cause mortality.
Results Normal-weight patients (BMI 18.5 to 25 kg/ m2) were older with more advanced HF and lower cardiometabolic risk. Despite worldwide heterogeneity in clinical features across obesity categories, a higher BMI remained associated with decreased 30-day and 1-year mortality (11% decrease at 30 days; 9% decrease at 1 year per 5 kg/ m2; p < 0.05), after adjustment for clinical risk. The BMI obtained at index admission provided effective 1-year risk reclassification beyond current markers of clinical risk (net reclassification index 0.119, p < 0.001). Notably, the "protective" association of BMI with mortality was confined to persons with older age (> 75 years; hazard ratio [HR]: 0.82; p 0.006), decreased cardiac function (ejection fraction < 50%; HR: 0.85; p < 0.001), no diabetes (HR: 0.86; p < 0.001), and de novo HF (HR: 0.89; p 0.004).
Conclusions A lower BMI is associated with age, disease severity, and a higher risk of death in acute decompensated HF. The "obesity paradox" is confined to older persons, with decreased cardiac function, less cardiometabolic illness, and recent-onset HF, suggesting that aging, HF severity/chronicity, and metabolism may explain the obesity paradox. (c) 2014 by the American College of Cardiology Foundation
C1 [Shah, Ravi; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
[Gayat, Etienne] Univ Paris Diderot, Lariboisiere Univ Hosp, AP HP, Dept Anesthesiol & Intens Care, Paris, France.
[Sato, Naoki] Musashi Kosugi Hosp, Nippon Med Sch, Tokyo, Japan.
[Cohen-Solal, Alain] INSERM, UMR 942, Paris, France.
[diSomma, Salvatore] Univ Roma La Sapienza, Emergency Dept, St Andrea Hosp, I-00185 Rome, Italy.
[Fairman, Enrique] Area Invest SAC Azcuenaga, Soc Argentina Cardiol, Buenos Aires, DF, Argentina.
[Harjola, Veli-Pekka] Univ Helsinki, Cent Hosp, Div Emergency Care, Helsinki, Finland.
[Ishihara, Shiro] Steel Mem Yawata Hosp, Dept Cardiol, Kitakyushu, Fukuoka, Japan.
[Lassus, Johan; Mebazaa, Alexandre] Univ Helsinki, Cent Hosp, Dept Med, Helsinki, Finland.
[Maggioni, Aldo] ANMCO Res Ctr, Florence, Italy.
[Metra, Marco] Univ Brescia, Dept Expt & Appl Med, Brescia, Italy.
[Mueller, Christian] Univ Basel Hosp, Dept Internal Med, CH-4031 Basel, Switzerland.
[Mueller, Thomas] Konventhosp Barmherzige Brueder, Dept Lab Med, Linz, Austria.
[Parenica, Jiri; Spinar, Jindrich] Masaryk Univ, Fac Med, Univ Hosp Brno, Dept Internal Med & Cardiol, Brno, Czech Republic.
[Pascual-Figal, Domingo] Univ Murcia, Fac Med, Dept Med, Cardiol Serv,Virgen de la Arrixaca Hosp, Murcia, Spain.
[Peacock, William Frank] Baylor Coll Med, Houston, TX 77030 USA.
[van Kimmenade, Roland] Univ Med Ctr, Utrecht, Netherlands.
RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Dept Cardiol, 32 Fruit St,Yawkey 5984, Boston, MA 02114 USA.
EM jjanuzzi@partners.org
RI Harjola, Veli-Pekka/G-9229-2015; Kimmenade, R.R.J./L-4432-2015;
OI Metra, Marco/0000-0001-6691-8568; Pascual Figal, Domingo
A./0000-0002-4993-9540
FU Servier; Roche Diagnostics; Siemens Diagnostics; Critical Diagnostics;
Thermo-Fisher Diagnostics; Alere; Abbott; Baxter; Brahms AG; Novartis;
Medicines Company; Eli Lily and Company
FX Dr. Gayat has received speaker's honoraria from Bristol-Myers Squibb;
and has received travel fees from Servier. Dr. Januzzi has received
grants from Roche Diagnostics, Siemens Diagnostics, Critical
Diagnostics, and Thermo-Fisher Diagnostics; and has received consultant
fees from Roche Diagnostics and Critical Diagnostics. Dr. diSomma has
received consultant fees from Alere and Thermo-Fisher Diagnostics. Dr.
Harjola has received consultant fees from Roche Diagnostics. Dr. Lassus
has received speaker's honoraria from Abbott; and has received
consultant fees from Roche Diagnostics. Dr. C. Mueller has received
research support and speaker's honoraria from Brahms AG, Alere, Abbott,
and Critical Diagnostics. Dr. T. Mueller has received speaker's
honoraria from Abbott Diagnostics, Brahms AG, and Roche Diagnostics. Dr.
Pascual-Figal has received grants from Roche Diagnostics. Dr. Peacock
has received research grants from Abbott, Alere, Baxter, Brahms AG,
Novartis, and The Medicines Company; has received consultant fees from
Abbott, Alere, Eli Lily and Company, and The Medicines Company; has
received speaker's honoraria from Abbott, and Alere; and has ownership
interest in Comprehensive Research Associates LLC, Vital Sensors, and
Emergencies in Medicine LLC. Dr. Mebazaa has received speaker's
honoraria from Alere, Brahms AG, Edwards, Orion, and Bayer. All other
authors have reported that they have no relationships relevant to the
contents of this paper to disclose.
NR 36
TC 70
Z9 72
U1 1
U2 16
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 4
PY 2014
VL 63
IS 8
BP 778
EP 785
DI 10.1016/j.jacc.2013.09.072
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AB3WM
UT WOS:000331720900005
PM 24315906
ER
PT J
AU Ky, B
Putt, M
Sawaya, H
French, B
Januzzi, JL
Sebag, IA
Plana, JC
Cohen, V
Banchs, J
Carver, JR
Wiegers, SE
Martin, RP
Picard, MH
Gerszten, RE
Halpern, EF
Passeri, J
Kuter, I
Scherrer-Crosbie, M
AF Ky, Bonnie
Putt, Mary
Sawaya, Heloisa
French, Benjamin
Januzzi, James L., Jr.
Sebag, Igal A.
Plana, Juan Carlos
Cohen, Victor
Banchs, Jose
Carver, Joseph R.
Wiegers, Susan E.
Martin, Randolph P.
Picard, Michael H.
Gerszten, Robert E.
Halpern, Elkan F.
Passeri, Jonathan
Kuter, Irene
Scherrer-Crosbie, Marielle
TI Early Increases in Multiple Biomarkers Predict Subsequent Cardiotoxicity
in Patients With Breast Cancer Treated With Doxorubicin, Taxanes, and
Trastuzumab
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE cardio-oncology; chemotherapy cardiotoxicity; trastuzumab cardiotoxicity
ID CHRONIC HEART-FAILURE; RISK STRATIFICATION; TROPONIN-I; PROGNOSTIC
VALUE; MYELOPEROXIDASE; ECHOCARDIOGRAPHY; ANTHRACYCLINE; TRIALS
AB Objectives The aim of this study was to determine if individual or multiple biomarkers are associated with cardiotoxicity in patients with breast cancer undergoing cancer therapy.
Background Current methods to identify patients at risk for cardiotoxicity from cancer therapy are inadequate.
Methods We measured 8 biomarkers in a multicenter cohort of 78 patients with breast cancer undergoing doxorubicin and trastuzumab therapy: ultrasensitive troponin I (TnI), high-sensitivity C-reactive protein (CRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor (GDF)-15, myeloperoxidase (MPO), placental growth factor (PlGF), soluble fms-like tyrosine kinase receptor (sFlt)-1, and galectin (gal)-3. Cardiotoxicity, defined by the Cardiac Review and Evaluation Committee criteria, was assessed every 3 months for up to 15 months. Hazard ratios (HRs) of cardiotoxicity risk were assessed for each biomarker at baseline, at visit 2 (3 months), and as a function of the difference between visit 2 and baseline. Joint models were assessed for the most promising biomarkers.
Results TnI, CRP, GDF-15, MPO, PlGF, and sFlt-1 levels increased from baseline to visit 2 (p < 0.05). A greater risk of cardiotoxicity was associated with interval changes in TnI (HR: 1.38 per SD; 95% confidence interval: 1.05 to 1.81; p = 0.02) and MPO (HR: 1.34 per SD; 95% confidence interval: 1.00 to 1.80; p = 0.048) and in models combining both markers (p = 0.007 and p = 0.03, respectively). The risk of cardiotoxicity was 46.5% in patients with the largest changes in both markers (DTnI > 121.8 mg/l; DMPO > 422.6 pmol/l).
Conclusions Early increases in TnI and MPO levels offer additive information about the risk of cardiotoxicity in patients undergoing doxorubicin and trastuzumab therapy. Independent validation of these findings is necessary before application to clinical practice. (C) 2014 by the American College of Cardiology Foundation
C1 [Ky, Bonnie; Putt, Mary; French, Benjamin; Carver, Joseph R.] Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Ky, Bonnie; Putt, Mary; French, Benjamin] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Sawaya, Heloisa; Januzzi, James L., Jr.; Picard, Michael H.; Gerszten, Robert E.; Passeri, Jonathan; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA.
[Sawaya, Heloisa; Januzzi, James L., Jr.; Picard, Michael H.; Gerszten, Robert E.; Passeri, Jonathan; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Sawaya, Heloisa; Januzzi, James L., Jr.; Picard, Michael H.; Gerszten, Robert E.; Halpern, Elkan F.; Passeri, Jonathan; Kuter, Irene; Scherrer-Crosbie, Marielle] Harvard Univ, Sch Med, Boston, MA USA.
[Sebag, Igal A.] Sir Mortimer B Davis Jewish Hosp, Echocardiog Lab, Montreal, PQ, Canada.
[Sebag, Igal A.] Sir Mortimer B Davis Jewish Hosp, Div Cardiol, Montreal, PQ, Canada.
[Sebag, Igal A.; Cohen, Victor] McGill Univ, Montreal, PQ, Canada.
[Plana, Juan Carlos] Cleveland Clin Fdn, Div Cardiovasc Med, Cleveland, OH 44195 USA.
[Cohen, Victor] Sir Mortimer B Davis Jewish Hosp, Segal Canc Ctr, Dept Med, Montreal, PQ, Canada.
[Banchs, Jose] Univ Texas MD Anderson Canc Ctr, Dept Cardiovasc Med, Houston, TX 77030 USA.
[Wiegers, Susan E.] Temple Univ, Div Cardiovasc Med, Philadelphia, PA 19122 USA.
[Martin, Randolph P.] Piedmont Heart Inst, Atlanta, GA USA.
[Halpern, Elkan F.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
[Kuter, Irene] Massachusetts Gen Hosp, Gillette Ctr Breast Canc, Boston, MA 02114 USA.
RP Ky, B (reprint author), Univ Penn, Sch Med, Smilow Translat Res Ctr, 11-105,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM bonnie.ky@uphs.upenn.edu; marielle@crosbie.com
OI Picard, Michael/0000-0002-9264-3243
FU Abbott Diagnostics; Critical Diagnostics; Roche Diagnostics; Siemens; BG
Medicine; Thermo Fisher; Singulex; BRAHMS; Siemens Ultrasound
FX The funding organizations, Abbott Diagnostics, and Siemens did not have
a role in the design or the conduct of the study; collection,
management, analysis, or interpretation of the data; or preparation,
review, or approval of the manuscript. Dr. Januzzi has received research
funding from Critical Diagnostics, Roche Diagnostics, Siemens, BG
Medicine, Thermo Fisher, Singulex, and BRAHMS. Dr. Wiegers holds stock
in Merck & Co, Inc. Dr. Martin has received research support from
Siemens Ultrasound and has received honoraria from Medtronic Heart
Valve, Edwards Lifesciences, and Sorin. Dr. Halpern has served as a
consultant for Hologic. All other authors have reported that they have
no relationships relevant to the content of this paper to disclose.
NR 25
TC 78
Z9 84
U1 1
U2 20
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD MAR 4
PY 2014
VL 63
IS 8
BP 809
EP 816
DI 10.1016/j.jacc.2013.10.061
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AB3WM
UT WOS:000331720900010
PM 24291281
ER
PT J
AU Lau, AN
Curtis, SJ
Fillmore, CM
Rowbotham, SP
Mohseni, M
Wagner, DE
Beede, AM
Montoro, DT
Sinkevicius, KW
Walton, ZE
Barrios, J
Weiss, DJ
Camargo, FD
Wong, KK
Kim, CF
AF Lau, Allison N.
Curtis, Stephen J.
Fillmore, Christine M.
Rowbotham, Samuel P.
Mohseni, Morvarid
Wagner, Darcy E.
Beede, Alexander M.
Montoro, Daniel T.
Sinkevicius, Kerstin W.
Walton, Zandra E.
Barrios, Juliana
Weiss, Daniel J.
Camargo, Fernando D.
Wong, Kwok-Kin
Kim, Carla F.
TI Tumor-propagating cells and Yap/Taz activity contribute to lung tumor
progression and metastasis
SO EMBO JOURNAL
LA English
DT Article
DE CD24; lung cancer; metastasis; Taz; tumor propagating cells
ID CANCER STEM-CELLS; INITIATING CELLS; BREAST-CANCER; ALDEHYDE
DEHYDROGENASE; EXPRESSION PROFILES; SELF-RENEWAL; ADENOCARCINOMA;
IDENTIFICATION; POPULATION; INVASION
AB Metastasis is the leading cause of morbidity for lung cancer patients. Here we demonstrate that murine tumor propagating cells (TPCs) with the markers Sca1 and CD24 are enriched for metastatic potential in orthotopic transplantation assays. CD24 knockdown decreased the metastatic potential of lung cancer cell lines resembling TPCs. In lung cancer patient data sets, metastatic spread and patient survival could be stratified with a murine lung TPC gene signature. The TPC signature was enriched for genes in the Hippo signaling pathway. Knockdown of the Hippo mediators Yap1 or Taz decreased in vitro cellular migration and transplantation of metastatic disease. Furthermore, constitutively active Yap was sufficient to drive lung tumor progression in vivo. These results demonstrate functional roles for two different pathways, CD24-dependent and Yap/Taz-dependent pathways, in lung tumor propagation and metastasis. This study demonstrates the utility of TPCs for identifying molecules contributing to metastatic lung cancer, potentially enabling the therapeutic targeting of this devastating disease.
C1 [Lau, Allison N.; Curtis, Stephen J.; Fillmore, Christine M.; Rowbotham, Samuel P.; Mohseni, Morvarid; Beede, Alexander M.; Montoro, Daniel T.; Sinkevicius, Kerstin W.; Barrios, Juliana; Camargo, Fernando D.; Kim, Carla F.] Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA.
[Lau, Allison N.; Curtis, Stephen J.; Fillmore, Christine M.; Rowbotham, Samuel P.; Mohseni, Morvarid; Beede, Alexander M.; Montoro, Daniel T.; Sinkevicius, Kerstin W.; Barrios, Juliana; Camargo, Fernando D.; Kim, Carla F.] Harvard Stem Cell Inst, Cambridge, MA USA.
[Lau, Allison N.; Curtis, Stephen J.; Fillmore, Christine M.; Rowbotham, Samuel P.; Beede, Alexander M.; Montoro, Daniel T.; Sinkevicius, Kerstin W.; Barrios, Juliana; Kim, Carla F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Mohseni, Morvarid; Camargo, Fernando D.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Wagner, Darcy E.; Weiss, Daniel J.] Univ Vermont, Dept Med, Burlington, VT USA.
[Walton, Zandra E.; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Walton, Zandra E.; Wong, Kwok-Kin] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.
[Walton, Zandra E.; Wong, Kwok-Kin] Harvard Canc Ctr, Ludwig Ctr Dana Farber, Boston, MA USA.
RP Kim, CF (reprint author), Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA.
EM carla.kim@childrens.harvard.edu
OI wong, kwok kin/0000-0001-6323-235X
FU DoD; Air Force Office of Scientific Research; National Defense Science
and Engineering Graduate Fellowships [32 CFR 168a]; American Cancer
Society [PF-09-121-01-DDC, PF-12-151-01-DMC]; Ladies Auxilliary to the
Veterans of Foreign Wars; Dana Farber Harvard Cancer Center Lung Cancer
SPORE grant [P50 CA090578, R01 AG2400401, R01 CA122794, R01 CA140594]; V
Foundation for Cancer Research; American Cancer Society Research Scholar
Grant [RSG-08-082-01-MGO]; Freeman Trust; Harvard Stem Cell Institute;
NIH/NHLBI [U01 HL100402, R01 HL090136]; Lung Cancer Alliance
FX We thank the DFCI, BIDMC, and CHB HemOnc FACS facilities, M. Correll and
S. Duan of the DFCI Center for Computational Cancer Biology, and members
of the Kim Lab for technical assistance and discussions, R. Bronson for
histopathology, L. Zon, C. Cepko, S. Armstrong, and W. Hahn for helpful
discussions. This work was supported by DoD, Air Force Office of
Scientific Research, National Defense Science and Engineering Graduate
Fellowships, 32 CFR 168a (to S.J.C. and A.N.L.), PF-09-121-01-DDC and
PF-12-151-01-DMC from the American Cancer Society (to K.W.S. and C.M.F.,
respectively), the Ladies Auxilliary to the Veterans of Foreign Wars (to
C.M.F.), Dana Farber Harvard Cancer Center Lung Cancer SPORE grant P50
CA090578, R01 AG2400401, R01 CA122794, R01 CA140594 (to K-K.W.), the V
Foundation for Cancer Research, American Cancer Society Research Scholar
Grant #RSG-08-082-01-MGO, the Freeman Trust, the Harvard Stem Cell
Institute, NIH/NHLBI U01 HL100402 and R01 HL090136 and The Lung Cancer
Alliance (to C.F.K.).
NR 50
TC 57
Z9 62
U1 2
U2 27
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0261-4189
EI 1460-2075
J9 EMBO J
JI Embo J.
PD MAR 3
PY 2014
VL 33
IS 5
BP 468
EP 481
DI 10.1002/embj.201386082
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AC3CC
UT WOS:000332391600009
PM 24497554
ER
PT J
AU Laitman, BM
Gajewski, ND
Mann, GL
Kubin, L
Morrison, AR
Ross, RJ
AF Laitman, Benjamin M.
Gajewski, Nicholas D.
Mann, Graziella L.
Kubin, Leszek
Morrison, Adrian R.
Ross, Richard J.
TI The alpha(1) adrenoceptor antagonist prazosin enhances sleep continuity
in fear-conditioned Wistar-Kyoto rats
SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Fear conditioning; Norepinephrine; Posttraumatic stress disorder; REM
sleep; Wistar-Kyoto rats
ID POSTTRAUMATIC-STRESS-DISORDER; RECEPTOR MESSENGER-RNA; EYE-MOVEMENT
SLEEP; NEURONS IN-VITRO; NON-REM SLEEP; BRAIN NOREPINEPHRINE; DEPENDENT
PLASTICITY; CLONIDINE INJECTIONS; COMBAT VETERANS; WKY RATS
AB Fragmentation of rapid eye movement sleep (REMS) is well described in individuals with posttraumatic stress disorder (PTSD) and likely has significant functional consequences. Fear-conditioned rodents may offer an attractive-model of the changes in sleep that characterize PTSD. Following fear conditioning (FC), Wistar-Kyoto (WKY) rats, a strain known to be particularly stress-sensitive, have increased REMS fragmentation that can be quantified as a shift in the distribution of REMS episodes towards themore frequent occurrence of sequential REMS (inter-REMS episode interval <= 3min) vs. single REMS(interval > 3min). The alpha(1) adrenoceptor antagonist prazosin has demonstrated efficacy in normalizing sleep in PTSD. To determine the utility of fear-conditioned WKY rats as a model of sleep disturbances typical of PTSD and as a platformfor the development of new treatments, we tested the hypothesis that prazosin would reduce REMS fragmentation in fear-conditionedWKY rats. Sleep parameters and freezing (a standardmeasure of anxiety in rodents) were quantified at baseline and on Days 1, 7, and 14 following FC, with either prazosin (0.01 mg/kg, i. p.) or vehicle injections administered prior to testing in a betweengroup design. Fear conditioning was achieved by pairing tones with a mild electric foot shock (1.0 mA, 0.5 s). One, 7, and 14 days following FC, prazosin or vehicle was injected, the tone was presented, freezing was measured, and then sleep was recorded from 11 AM to 3 PM. WKY rats given prazosin, compared to those given vehicle, had a lower amount of seq-REMS relative to total REMS time 14 days after FC. They also had a shorter nonREMS latency and fewer non-REMS arousals at baseline and on Days 1 and 7 after FC. Thus, in FC rats, prazosin reduced both REMS fragmentation and non-REMS discontinuity. Published by Elsevier Inc.
C1 [Laitman, Benjamin M.; Gajewski, Nicholas D.; Mann, Graziella L.; Kubin, Leszek; Morrison, Adrian R.; Ross, Richard J.] Univ Penn, Sch Vet Med, Dept Anim Biol, Philadelphia, PA 19104 USA.
[Ross, Richard J.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Ross, Richard J.] Vet Affairs Med Ctr, Philadelphia, PA USA.
RP Laitman, BM (reprint author), Mt Sinai Sch Med, Grad Sch Biol Sci, 1 Gustave L Levy Pl, New York, NY 10029 USA.
EM benjamin.laitman@mssm.edu
FU NIH [RO1-MH072897]
FX The study was supported by NIH grant RO1-MH072897. The authors thank Dr.
Philip R. Gehrman for his assistance with statistical analysis. The
views presented in this article do not represent those of the Department
of Veterans Affairs or of the US Government.
NR 61
TC 2
Z9 2
U1 1
U2 12
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0278-5846
J9 PROG NEURO-PSYCHOPH
JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry
PD MAR 3
PY 2014
VL 49
BP 7
EP 15
DI 10.1016/j.pnpbp.2013.11.004
PG 9
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 280WA
UT WOS:000329060300002
PM 24246572
ER
PT J
AU Boyd, JE
Otilingam, PG
DeForge, BR
AF Boyd, Jennifer E.
Otilingam, Poorni G.
DeForge, Bruce R.
TI Brief Version of the Internalized Stigma of Mental Illness (ISMI) Scale:
Psychometric Properties and Relationship to Depression, Self Esteem,
Recovery Orientation, Empowerment, and Perceived Devaluation and
Discrimination
SO PSYCHIATRIC REHABILITATION JOURNAL
LA English
DT Article
DE stigma of mental illness; questionnaire; depression; self-esteem;
empowerment
ID PEOPLE; CONSEQUENCES; SCHIZOPHRENIA; EXPERIENCES; OUTPATIENTS;
DISORDERS; VALIDITY; PARADOX; MODEL
AB Objective: The internalized stigma of mental illness impedes recovery and is associated with increased depression, reduced self-esteem, reduced recovery orientation, reduced empowerment, and increased perceived devaluation and discrimination. The Internalized Stigma of Mental Illness (ISMI) scale is a 29-item self-report questionnaire developed with consumer input that includes the following subscales: Alienation, Discrimination Experience, Social Withdrawal, Stereotype Endorsement, and Stigma Resistance. Here we present a 10-item version of the ISMI containing the two strongest items from each subscale. Method: Participants were all outpatient veterans with serious mental illness. Following the rigorous scale-reduction methods set forth by Stanton and colleagues (2002), we selected the 10 items, tested the psychometrics of the shortened scale in the original validation sample (N = 127), and cross-checked the results in a second dataset (N = 760). Results: As expected, the ISMI-10 retained the essential properties of the ISMI-29, including adequate internal consistency reliability and external validity in relation to depression, self-esteem, recovery orientation, perceived devaluation and discrimination, and empowerment. The ISMI-10 scores are normally distributed and have similar descriptive statistics to the ISMI-29. The reliability and depression findings were replicated in a cross-validation sample. Conclusions and Implications for Practice: We conclude that the ISMI-10 has strong psychometric properties and is a practical, reliable, and valid alternative to the original ISMI-29. Future work should test the ISMI-10 in more diverse samples. This shorter version should reduce respondent burden in program evaluation projects that seek to determine whether participation in psychosocial rehabilitation programming reduces internalized stigma.
C1 [Boyd, Jennifer E.] San Francisco VA Med Ctr, Dept Psychiat, San Francisco, CA 94121 USA.
[Boyd, Jennifer E.] Univ Calif San Francisco, San Francisco, CA 94121 USA.
[Otilingam, Poorni G.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA 94121 USA.
[DeForge, Bruce R.] Univ Maryland, Sch Social Work, Baltimore, MD 21201 USA.
RP Boyd, JE (reprint author), San Francisco VA Med Ctr, Dept Psychiat, 4150 Clement St 116A, San Francisco, CA 94121 USA.
EM jennifer.boyd@va.gov
NR 38
TC 10
Z9 10
U1 4
U2 16
PU CENTER PSYCHIATRIC REHABILITATION
PI BOSTON
PA BOSTON UNIV, 930 COMMONWEALTH AVE, BOSTON, MA 02215 USA
SN 1095-158X
EI 1559-3126
J9 PSYCHIATR REHABIL J
JI Psychiatr. Rehabil. J.
PD MAR
PY 2014
VL 37
IS 1
BP 17
EP 23
DI 10.1037/prj0000035
PG 7
WC Psychiatry; Rehabilitation
SC Psychiatry; Rehabilitation
GA CA0RP
UT WOS:000348624600004
PM 24660946
ER
PT J
AU Beehler, S
Clark, JA
Eisen, SV
AF Beehler, Sarah
Clark, Jack A.
Eisen, Susan V.
TI Participant Experiences in Peer- and Clinician-Facilitated Mental Health
Recovery Groups for Veterans
SO PSYCHIATRIC REHABILITATION JOURNAL
LA English
DT Article
DE mental health recovery; veteran; peer support; qualitative
ID PARTNER INTERDEPENDENCE ANALYSIS; GROUP-PSYCHOTHERAPY; PROVIDED
SERVICES; SUPPORT; CONSUMER; ILLNESS; SESSION; BEHAVIORS; ALLIANCE;
CLIENTS
AB Objective: The purpose of the study was to characterize and compare participants' experiences of peer-facilitated versus clinician-facilitated recovery groups for veterans with mental illness. Method: We analyzed qualitative data from 24 interviews with veterans who participated in mental health recovery groups led by peer or clinician facilitators. Results: Subtle differences in group structure, participation/communication and utility/relevance between peer- and clinician-facilitated groups were identified. Participants experienced both peer and clinician facilitators as helpful in promoting recovery, though they appeared to do this in different ways. Conclusions and Implications for Practice: Peer and clinician facilitators offer different strengths in the promotion of mental health recovery.
C1 [Beehler, Sarah] VA Boston Healthcare Syst, CHOIR, Jamaica Plain, MA USA.
[Beehler, Sarah] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA.
[Clark, Jack A.; Eisen, Susan V.] Edith Nourse Rogers Mem Vet Hosp, CHOIR, Bedford, MA USA.
[Clark, Jack A.; Eisen, Susan V.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA.
RP Beehler, S (reprint author), Univ Minnesota, Sch Med, Dept Biobehav Hlth & Populat Sci, Duluth Campus,1035 Univ Dr,SMed 241, Duluth, MN 55812 USA.
EM sjbeehle@d.umn.edu
NR 28
TC 1
Z9 1
U1 3
U2 3
PU CENTER PSYCHIATRIC REHABILITATION
PI BOSTON
PA BOSTON UNIV, 930 COMMONWEALTH AVE, BOSTON, MA 02215 USA
SN 1095-158X
EI 1559-3126
J9 PSYCHIATR REHABIL J
JI Psychiatr. Rehabil. J.
PD MAR
PY 2014
VL 37
IS 1
BP 43
EP 50
DI 10.1037/prj0000048
PG 8
WC Psychiatry; Rehabilitation
SC Psychiatry; Rehabilitation
GA CA0RP
UT WOS:000348624600008
PM 24660950
ER
PT J
AU Fazeli, PK
Klibanski, A
AF Fazeli, Pouneh K.
Klibanski, Anne
TI Bone Metabolism in Anorexia Nervosa
SO CURRENT OSTEOPOROSIS REPORTS
LA English
DT Article
DE Anorexia nervosa; Bone mineral density
ID GROWTH-FACTOR-I; HYPOTHALAMIC-PITUITARY FUNCTION; LOW SERUM
TRIIODOTHYRONINE; THYROID-HORMONE RECEPTORS; IGF-BINDING PROTEINS;
ADOLESCENT GIRLS; HEALTHY ADOLESCENTS; SECRETORY DYNAMICS; YOUNG-WOMEN;
MINERAL DENSITY
AB Anorexia nervosa (AN), a psychiatric disorder predominantly affecting young women, is characterized by self-imposed, chronic nutritional deprivation and distorted body image. AN is associated with a number of medical comorbidities including low bone mass. The low bone mass in AN is due to an uncoupling of bone formation and bone resorption, which is the result of hormonal adaptations aimed at decreasing energy expenditure during periods of low energy intake. Importantly, the low bone mass in AN is associated with a significant risk of fractures and therefore treatments to prevent bone loss are critical. In this review, we discuss the hormonal determinants of low bone mass in AN and treatments that have been investigated in this population.
C1 [Fazeli, Pouneh K.; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
RP Fazeli, PK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,Bulfinch 457, Boston, MA 02114 USA.
EM pkfazeli@partners.org
FU NIH [K23 DK094820, R24 DK092759]
FX PK Fazeli has received research support from the NIH (K23 DK094820). A
Klibanski has received research supplies from Ipsen (drug and placebo
only for study) and Eli Lilly (drug and placebo only for study); and
research support from the NIH (R24 DK092759).
NR 96
TC 8
Z9 8
U1 2
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
EI 1544-2241
J9 CURR OSTEOPOROS REP
JI Curr. Osteoporos. Rep.
PD MAR
PY 2014
VL 12
IS 1
BP 82
EP 89
DI 10.1007/s11914-013-0186-8
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AY0IZ
UT WOS:000347281700011
PM 24419863
ER
PT J
AU Huckans, M
Fuller, BE
Olavarria, H
Sasaki, AW
Chang, M
Flora, KD
Kolessar, M
Kriz, D
Anderson, JR
Vandenbark, AA
Loftis, JM
AF Huckans, Marilyn
Fuller, Bret E.
Olavarria, Hannah
Sasaki, Anna W.
Chang, Michael
Flora, Kenneth D.
Kolessar, Michael
Kriz, Daniel
Anderson, Jeanne R.
Vandenbark, Arthur A.
Loftis, Jennifer M.
TI Multi-analyte profile analysis of plasma immune proteins: altered
expression of peripheral immune factors is associated with
neuropsychiatric symptom severity in adults with and without chronic
hepatitis C virus infection
SO BRAIN AND BEHAVIOR
LA English
DT Article
DE Anxiety; biological markers; chronic infection; cytokines; depression;
fatigue; pain
ID MAJOR DEPRESSIVE DISORDER; NECROSIS-FACTOR-ALPHA; INTERFERON-INDUCED
DEPRESSION; QUALITY-OF-LIFE; NEUROTROPHIC FACTOR; CYTOKINE LEVELS;
TNF-ALPHA; HEPATOCELLULAR-CARCINOMA; BEHAVIORAL CONSEQUENCES;
PSYCHIATRIC-DISORDERS
AB Background: The purpose of this study was to characterize hepatitis C virus (HCV)-associated differences in the expression of 47 inflammatory factors and to evaluate the potential role of peripheral immune activation in HCV-associated neuropsychiatric symptoms-depression, anxiety, fatigue, and pain. An additional objective was to evaluate the role of immune factor dysregulation in the expression of specific neuropsychiatric symptoms to identify biomarkers that may be relevant to the treatment of these neuropsychiatric symptoms in adults with or without HCV. Methods: Blood samples and neuropsychiatric symptom severity scales were collected from HCV-infected adults (HCV+, n = 39) and demographically similar noninfected controls (HCV-, n = 40). Multi-analyte profile analysis was used to evaluate plasma biomarkers. Results: Compared with HCV- controls, HCV+ adults reported significantly (P < 0.050) greater depression, anxiety, fatigue, and pain, and they were more likely to present with an increased inflammatory profile as indicated by significantly higher plasma levels of 40% (19/47) of the factors assessed (21%, after correcting for multiple comparisons). Within the HCV+ group, but not within the HCV- group, an increased inflammatory profile (indicated by the number of immune factors > the LDC) significantly correlated with depression, anxiety, and pain. Within the total sample, neuropsychiatric symptom severity was significantly predicted by protein signatures consisting of 4-10 plasma immune factors; protein signatures significantly accounted for 19-40% of the variance in depression, anxiety, fatigue, and pain. Conclusions: Overall, the results demonstrate that altered expression of a network of plasma immune factors contributes to neuropsychiatric symptom severity. These findings offer new biomarkers to potentially facilitate pharmacotherapeutic development and to increase our understanding of the molecular pathways associated with neuropsychiatric symptoms in adults with or without HCV.
C1 [Huckans, Marilyn; Fuller, Bret E.; Olavarria, Hannah; Vandenbark, Arthur A.; Loftis, Jennifer M.] Portland VA Med Ctr, Res & Dev Serv, Portland, OR 97239 USA.
[Huckans, Marilyn; Fuller, Bret E.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR 97239 USA.
[Huckans, Marilyn; Loftis, Jennifer M.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA.
[Sasaki, Anna W.; Chang, Michael] Portland VA Med Ctr, Gastroenterol Serv, Portland, OR 97239 USA.
[Sasaki, Anna W.; Chang, Michael] Oregon Hlth & Sci Univ, Dept Internal Med, Portland, OR 97239 USA.
[Flora, Kenneth D.] Oregon Clin, Portland Gastroenterol Div, Clackamas, OR 97015 USA.
[Kolessar, Michael; Kriz, Daniel; Anderson, Jeanne R.] Pacific Univ, Sch Profess Psychol, Hillsboro, OR 97123 USA.
[Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA.
[Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA.
RP Loftis, JM (reprint author), Portland VA Med Ctr, R&D 16, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA.
EM loftisj@ohsu.edu
FU Department of Veterans Affairs, Veterans Health Administration, Office
of Research and Development, Clinical Sciences Research and Development
FX This study was supported by career development awards to M. Huckans
(Staff Psychologist and Neuropsychologist) and J. M. Loftis (Research
Scientist) from the Department of Veterans Affairs, Veterans Health
Administration, Office of Research and Development, Clinical Sciences
Research and Development.
NR 131
TC 11
Z9 12
U1 1
U2 3
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 2162-3279
J9 BRAIN BEHAV
JI Brain Behav.
PD MAR
PY 2014
VL 4
IS 2
BP 123
EP 142
DI 10.1002/brb3.200
PG 20
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA AX5NJ
UT WOS:000346973200003
PM 24683507
ER
PT J
AU Litt, JS
Perrin, JM
AF Litt, Jonathan S.
Perrin, James M.
TI Influence of Clinical and Sociodemographic Characteristics on Early
Intervention Enrollment After NICU Discharge
SO JOURNAL OF EARLY INTERVENTION
LA English
DT Article
DE high-risk infant; low-birth-weight infant; early intervention; special
services
ID LOW-BIRTH-WEIGHT; CHILDREN BORN; OUTCOMES; PRETERM; INFANTS; AGE;
EXPERIENCE
AB This study aims to characterize participation of neonatal intensive care unit (NICU) graduates in early intervention (EI). We used data from the National Early Intervention Longitudinal Study. We fit models of days from referral to Individualized Family Service Plan creation (plan time), days from referral to initiation of services (service time), and parent-reported effort to enroll their child with clinical and sociodemographic predictors. The sample of 1,188 NICU graduates had median birth weight 1,942 g, gestational age 33.4 weeks, and maternal age 27.4 years. Plan time was shorter for those with health insurance (2.5 weeks, p =.04) and living in high-providing states (3.3 weeks, p =.005). Service time was shorter for those with global delay (8 days, p =.02) and health insurance (11 days, p =.03) and longer for those with single parents (24 days, p =.009). Single parents and parents of children with higher birth weight, congenital problems, and non-White race reported greater effort finding services. Single parents and parents of female and higher birth weight infants reported greater effort initiating services. These findings document disparities in enrollment timing and service provision by disability types, single parenthood, and being of non-White race. Further elucidation of such disparities could lead to improved enrollment and access to prescribed services.
C1 [Litt, Jonathan S.] Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
[Litt, Jonathan S.; Perrin, James M.] Harvard Univ, Sch Med, Boston, MA USA.
[Perrin, James M.] MassGen Hosp Children, Boston, MA USA.
RP Litt, JS (reprint author), Beth Israel Deaconess Med Ctr, Dept Neonatol, 330 Brookline Ave,Rose 318, Boston, MA 02115 USA.
EM jlitt@bidmc.harvard.edu
NR 29
TC 2
Z9 2
U1 0
U2 2
PU COUNCIL EXCEPTIONAL CHILDREN
PI ARLINGTON
PA 1110 N GLEBE RD, ARLINGTON, VA 22201-5704 USA
SN 1053-8151
EI 2154-3992
J9 J EARLY INTERVENTION
JI J. Early Interv.
PD MAR
PY 2014
VL 36
IS 1
BP 37
EP 48
DI 10.1177/1053815114555575
PG 12
WC Education, Special; Psychology, Educational; Rehabilitation
SC Education & Educational Research; Psychology; Rehabilitation
GA AU5YL
UT WOS:000345679300003
ER
PT J
AU Truong, QA
Gewirtz, H
AF Truong, Quynh A.
Gewirtz, Henry
TI Cardiac PET-CT for Monitoring Medical and Interventional Therapy in
Patients with CAD: PET Alone Versus Hybrid PET-CT?
SO CURRENT CARDIOLOGY REPORTS
LA English
DT Article
DE Cardiac PET; Hybrid PET-CT; Myocardial blood flow; Coronary artery
disease; Treatment of CAD; Coronary flow reserve; Medical and
interventional therapy
ID POSITRON-EMISSION-TOMOGRAPHY; CORONARY-ARTERY-DISEASE;
ISCHEMIC-HEART-DISEASE; CARDIOVASCULAR MAGNETIC-RESONANCE;
MYOCARDIAL-PERFUSION RESERVE; APPROPRIATE USE CRITERIA; CHRONIC TOTAL
OCCLUSION; COMPUTED-TOMOGRAPHY; NUCLEAR CARDIOLOGY; DIAGNOSTIC-ACCURACY
AB This review focuses on optimal use of PET and PET-CT in monitoring medical and interventional therapy in patients with CAD. PET provides quantitative measurement of absolute myocardial blood flow and thus permits comprehensive physiological assessment of the coronary circulation. Hybrid PET-CT, in particular CCTA, adds anatomical information to maximal MBF measurement and so facilitates distinction of triple vessel focal epicardial disease from coronary microvascular disease or diffuse coronary atherosclerosis without focal stenoses. Hybrid PET-CT also may be of value in determining appropriateness and feasibility of percutaneous interventional therapy for chronic total coronary occlusion. PET alone, however, is the preferred modality to address functional status of the coronary circulation and response over time, if required, to medical or interventional therapy. CT at a minimum provides attenuation correction. More detailed CCTA should be added only when a well-defined need for anatomical information is required to answer the clinical question posed.
C1 [Truong, Quynh A.; Gewirtz, Henry] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div,Cardiac Unit, Boston, MA 02114 USA.
[Truong, Quynh A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Cardiac MR PET CT Program, Boston, MA 02114 USA.
RP Gewirtz, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div,Cardiac Unit, Yawkey 5E,55 Fruit St, Boston, MA 02114 USA.
EM hgewirtz@partners.org
FU NIH [K23HL098370, L30HL093896]; St. Jude's Medical; American College of
Radiology Imaging Network; Duke Clinical Research Institute; Wild Family
Foundation
FX Quynh A. Truong was supported by the NIH (K23HL098370 and L30HL093896)
and receives research grants from St. Jude's Medical, American College
of Radiology Imaging Network, and Duke Clinical Research Institute.;
Henry Gewirtz received partial support from an unrestricted grant from
the Wild Family Foundation.
NR 57
TC 1
Z9 1
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1523-3782
EI 1534-3170
J9 CURR CARDIOL REP
JI Curr. Cardiol. Rep.
PD MAR
PY 2014
VL 16
IS 3
AR 460
DI 10.1007/s11886-013-0460-5
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AT6ZD
UT WOS:000345084700007
PM 24464305
ER
PT J
AU Thompson, JM
Zamorski, MA
Sweet, J
VanTil, L
Sareen, J
Pietrzak, RH
Hopman, WH
MacLean, MB
Pedlar, D
AF Thompson, James M.
Zamorski, Mark A.
Sweet, Jill
VanTil, Linda
Sareen, Jitender
Pietrzak, Robert H.
Hopman, Wilma H.
MacLean, Mary Beth
Pedlar, David
TI Roles of physical and mental health in suicidal ideation in Canadian
Armed Forces Regular Force veterans
SO CANADIAN JOURNAL OF PUBLIC HEALTH-REVUE CANADIENNE DE SANTE PUBLIQUE
LA English
DT Article
DE Veterans; suicidal ideation; physical health; mental health; suicide
ID OLDER MALE VETERANS; RISK-FACTORS; MILITARY PERSONNEL; NATIONAL-HEALTH;
PREVALENCE; SOLDIERS; COMBAT; ASSOCIATION; AFGHANISTAN; PERSPECTIVE
AB OBJECTIVES: Suicide in recent veterans is an international concern. An association between mental disorders and suicide has been established, but less information is available about an association between physical health problems and suicide among veterans. This study extends this area of inquiry by examining the relationship of both physical and mental health problems with suicidal ideation in a representative national sample of Canadian veterans.
METHODS: Subjects were a stratified random sample of 2,658 veterans who had been released from the Canadian Armed Forces Regular Force during 1998-2007 and had participated in the 2010 Survey on Transition to Civilian Life. Associations between physical and mental health and past-year suicidal ideation were explored in multivariable regression models using three measures of physical and mental health.
RESULTS: The prevalence of suicidal ideation was 5.8% (95% confidence interval [CI]: 5.0%-6.8%). After adjustment for covariates, ideation was associated with gastrointestinal disorders (adjusted odds ratio [AOR] 1.66, CI: 1.03-2.65), depression or anxiety (AOR 5.06, CI: 2.97-8.62) and mood disorders (AOR 2.91, CI: 1.67-5.07); number of physical (AOR 1.22, CI: 1.05-1.42) and mental conditions (AOR 2.32, CI: 2.01-2.68); and SF-12 Health Survey physical health (AOR 0.98, CI: 0.96-0.99 for each 1 point increase) and mental health (AOR 0.88, CI: 0.87-0.89).
CONCLUSIONS: Physical health was independently associated with suicidal ideation after adjustment for mental health status and socio-demographic characteristics. The findings underscore the importance of considering physical health in population-based suicide prevention efforts and in mitigating suicide risk in individual veterans.
C1 [Thompson, James M.; Sweet, Jill; VanTil, Linda; MacLean, Mary Beth; Pedlar, David] Vet Affairs Canada, Res Directorate, Charlottetown, PE C1A 8M9, Canada.
[Thompson, James M.; Hopman, Wilma H.] Queens Univ, Dept Publ Hlth Sci, Kingston, ON, Canada.
[Zamorski, Mark A.] Canadian Forces Hlth Serv Grp, Directorate Mental Hlth, Ottawa, ON, Canada.
[Sareen, Jitender] Univ Manitoba, Dept Psychiat, Winnipeg, MB R3T 2N2, Canada.
[Sareen, Jitender] Univ Manitoba, Dept Psychol, Winnipeg, MB R3T 2N2, Canada.
[Sareen, Jitender] Univ Manitoba, Dept Community Hlth Sci, Winnipeg, MB R3T 2N2, Canada.
[Pietrzak, Robert H.] VA Connecticut Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, US Dept Vet Affairs, West Haven, CT USA.
[Pietrzak, Robert H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
[Hopman, Wilma H.] Kingston Gen Hosp, Clin Res Ctr, Kingston, ON K7L 2V7, Canada.
RP Thompson, JM (reprint author), Vet Affairs Canada, POB 7700,Rm 406 DJM Bldg,161 Grafton St, Charlottetown, PE C1A 8M9, Canada.
EM research-recherche@vac-acc.gc.ca
NR 31
TC 1
Z9 1
U1 4
U2 6
PU CANADIAN PUBLIC HEALTH ASSOC
PI OTTAWA
PA 1565 CARLING AVE, SUITE 300, OTTAWA, ONTARIO K1Z 8R1, CANADA
SN 0008-4263
EI 1920-7476
J9 CAN J PUBLIC HEALTH
JI Can. J. Public Health-Rev. Can. Sante Publ.
PD MAR-APR
PY 2014
VL 105
IS 2
BP E109
EP E115
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AS9UG
UT WOS:000344586200004
PM 24886845
ER
PT J
AU Manchikanti, L
Falco, FJE
Kaye, AD
Hirsch, JA
AF Manchikanti, Laxmaiah
Falco, Frank J. E.
Kaye, Alan D.
Hirsch, Joshua A.
TI The Disastrous but Preventable Consequences of ICD-10
SO PAIN PHYSICIAN
LA English
DT Article
ID READY
C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA.
[Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA.
[Falco, Frank J. E.] Mid Atlantic Spine & Pain Phys, Newark, DE USA.
[Falco, Frank J. E.] Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA.
[Kaye, Alan D.] LSU Hlth Sci Ctr, New Orleans, LA USA.
[Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA.
RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA.
EM drlm@thepainmd.com
NR 27
TC 6
Z9 6
U1 0
U2 0
PU AM SOC INTERVENTIONAL PAIN PHYSICIANS
PI PADUCAH
PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA
SN 1533-3159
J9 PAIN PHYSICIAN
JI Pain Physician
PD MAR-APR
PY 2014
VL 17
IS 2
BP E111
EP E118
PG 8
WC Anesthesiology; Clinical Neurology
SC Anesthesiology; Neurosciences & Neurology
GA AS7EX
UT WOS:000344421100013
PM 24658482
ER
PT J
AU Greaney, ML
De Jesus, M
Sprunck-Harrild, KM
Tellez, T
Bastani, R
Battaglia, TA
Michaelson, JS
Emmons, KM
AF Greaney, Mary L.
De Jesus, Maria
Sprunck-Harrild, Kim M.
Tellez, Trinidad
Bastani, Roshan
Battaglia, Tracy A.
Michaelson, James S.
Emmons, Karen M.
TI Designing Audience-Centered Interactive Voice Response Messages to
Promote Cancer Screenings Among Low-Income Latinas
SO PREVENTING CHRONIC DISEASE
LA English
DT Article
ID FORCE RECOMMENDATION STATEMENT; COMMUNITY-HEALTH-CENTER; SOCIETY
GUIDELINES; UNITED-STATES; CERVICAL-CANCER; INTERVENTION;
IMPLEMENTATION; PREVENTION; BARRIERS; BREAST
AB Introduction
Cancer screening rates among Latinas are suboptimal. The objective of this study was to explore how Latinas perceive cancer screening and the use and design of interactive voice response (IVR) messages to prompt scheduling of 1 or more needed screenings.
Methods
Seven focus groups were conducted with Latina community health center patients (n = 40) in need of 1 or more cancer screenings: 5 groups were of women in need of 1 cancer screening (breast, cervical, or colorectal), and 2 groups were of women in need of multiple screenings. A bilingual researcher conducted all focus groups in Spanish using a semistructured guide. Focus groups were recorded, transcribed, and translated into English for analysis. Emergent themes were identified by using thematic content analysis.
Results
Participants were familiar with cancer screening and viewed it positively, although barriers to screening were identified (unaware overdue for screening, lack of physician referral, lack of insurance or insufficient insurance coverage, embarrassment or fear of screening procedures, fear of screening outcomes). Women needing multiple screenings voiced more concern about screening procedures, whereas women in need of a single screening expressed greater worry about the screening outcome. Participants were receptive to receiving IVR messages and believed that culturally appropriate messages that specified needed screenings while emphasizing the benefit of preventive screening would motivate them to schedule needed screenings.
Conclusion
Participants' receptiveness to IVR messages suggests that these messages may be an acceptable strategy to promote cancer screening among underserved Latina patients. Additional research is needed to determine the effectiveness of IVR messages in promoting completion of cancer screening.
C1 [De Jesus, Maria] Amer Univ, Ctr Hlth Risk Soc, Washington, DC 20016 USA.
[De Jesus, Maria] Amer Univ, Sch Int Serv, Washington, DC 20016 USA.
[Sprunck-Harrild, Kim M.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA.
[Tellez, Trinidad] New Hampshire Dept Hlth & Human Serv, Concord, NH 03301 USA.
[Bastani, Roshan] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA.
[Battaglia, Tracy A.] Boston Med Ctr, Boston, MA USA.
[Battaglia, Tracy A.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Michaelson, James S.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Michaelson, James S.] Harvard Univ, Sch Med, Boston, MA USA.
[Emmons, Karen M.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
RP Greaney, ML (reprint author), Univ Rhode Isl, Dept Kinesiol, 25 West Independence Way, Kingston, RI 02881 USA.
EM mgreaney@mail.uri.edu
FU National Cancer Institute [5R01CA126596, 1K05 CA124415]
FX We thank the women who participated in this study and acknowledge Ms
Martha Cruz and Ms Jewnifer Grullon for their effort on behalf of this
research. This study was supported by grants from the National Cancer
Institute, 5R01CA126596 and 1K05 CA124415.
NR 31
TC 0
Z9 0
U1 0
U2 4
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 1545-1151
J9 PREV CHRONIC DIS
JI Prev. Chronic Dis.
PD MAR
PY 2014
VL 11
DI 10.5888/pcd11.130213N
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AR3XF
UT WOS:000343521800007
ER
PT J
AU Homer, ML
Perge, JA
Black, MJ
Harrison, MT
Cash, SS
Hochberg, LR
AF Homer, Mark L.
Perge, Janos A.
Black, Michael J.
Harrison, Matthew T.
Cash, Sydney S.
Hochberg, Leigh R.
TI Adaptive Offset Correction for Intracortical Brain-Computer Interfaces
SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING
LA English
DT Article
DE Adaptive filtering; brain-computer interfaces (BCI); brain-machine
interfaces (BMI); Kalman filter; motor cortex; neural decoding
ID NEURAL-CONTROL; MACHINE INTERFACES; PROSTHETIC DEVICES; CORTICAL
CONTROL; KALMAN FILTER; TETRAPLEGIA; ARM; ALGORITHM; MOVEMENT; DESIGN
AB Intracortical brain-computer interfaces (iBCIs) decode intended movement from neural activity for the control of external devices such as a robotic arm. Standard approaches include a calibration phase to estimate decoding parameters. During iBCI operation, the statistical properties of the neural activity can depart from those observed during calibration, sometimes hindering a user's ability to control the iBCI. To address this problem, we adaptively correct the offset terms within a Kalman filter decoder via penalized maximum likelihood estimation. The approach can handle rapid shifts in neural signal behavior (on the order of seconds) and requires no knowledge of the intended movement. The algorithm, called multiple offset correction algorithm (MOCA), was tested using simulated neural activity and evaluated retrospectively using data collected from two people with tetraplegia operating an iBCI. In 19 clinical research test cases, where a nonadaptive Kalman filter yielded relatively high decoding errors, MOCA significantly reduced these errors (10.6 +/- 10.1%; p < 0.05, pairwise t-test). MOCA did not significantly change the error in the remaining 23 cases where a nonadaptive Kalman filter already performed well. These results suggest that MOCA provides more robust decoding than the standard Kalman filter for iBCIs.
C1 [Homer, Mark L.] Brown Univ, Providence, RI 02912 USA.
[Perge, Janos A.; Hochberg, Leigh R.] Brown Univ, Sch Engn, Providence, RI 02912 USA.
[Black, Michael J.] Max Planck Inst Intelligent Syst, D-72076 Tubingen, Germany.
[Black, Michael J.] Brown Univ, Dept Comp Sci, Providence, RI 02912 USA.
[Harrison, Matthew T.] Brown Univ, Div Appl Math, Providence, RI 02912 USA.
[Cash, Sydney S.; Hochberg, Leigh R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Cash, Sydney S.; Hochberg, Leigh R.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Hochberg, Leigh R.] Dept Vet Affairs Med Ctr, Rehabil Res & Dev Serv, Ctr Neurorestorat & Neurotechnol, Providence, RI 02908 USA.
RP Homer, ML (reprint author), Brown Univ, Providence, RI 02912 USA.
EM mark_homer@brown.edu; janos_perge@brown.edu; black@tuebingen.mpg.de;
matthew_harrison@brown.edu; scash@partners.org; leigh_hochberg@brown.edu
OI Hochberg, Leigh/0000-0003-0261-2273
FU Rehabilitation Research and Development Service, Office of Research and
Development, Department of Veterans Affairs [B6453R, B6310N]; National
Institutes of Health: NIDCD [R01DC009899]; NICHD-NCMRR [N01HD53403,
N01HD10018]; DARPA REPAIR [N66001-10-C-2010]; Doris Duke Charitable
Foundation; MGH-Deane Institute for Integrated Research on Atrial
Fibrillation and Stroke
FX Manuscript received March 01, 2013; revised September 12, 2013; accepted
October 14, 2013. Date of publication November 01, 2013; date of current
version March 05, 2014. The research was supported by the Rehabilitation
Research and Development Service, Office of Research and Development,
Department of Veterans Affairs (Merit Review Award B6453R; Career
Development Transition Award B6310N). Support was also provided by the
National Institutes of Health: NIDCD (R01DC009899), NICHD-NCMRR
(N01HD53403 and N01HD10018); DARPA REPAIR (N66001-10-C-2010); the Doris
Duke Charitable Foundation; the MGH-Deane Institute for Integrated
Research on Atrial Fibrillation and Stroke. The pilot clinical trial
into which participant S3 was recruited was sponsored in part by
Cyberkinetics Neurotechnology Systems (CKI). The contents do not
represent the views of the Department of Veterans Affairs or the United
States Government.
NR 51
TC 1
Z9 3
U1 0
U2 4
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 1534-4320
EI 1558-0210
J9 IEEE T NEUR SYS REH
JI IEEE Trans. Neural Syst. Rehabil. Eng.
PD MAR
PY 2014
VL 22
IS 2
BP 239
EP 248
DI 10.1109/TNSRE.2013.2287768
PG 10
WC Engineering, Biomedical; Rehabilitation
SC Engineering; Rehabilitation
GA AP4VV
UT WOS:000342078300005
PM 24196868
ER
PT J
AU Cvetanovich, GL
Bhatia, S
Provencher, MT
Cole, BJ
AF Cvetanovich, Gregory L.
Bhatia, Sanjeev
Provencher, Matthew T.
Cole, Brian J.
TI Treatment of Bone Defects in Posterior Instability
SO OPERATIVE TECHNIQUES IN SPORTS MEDICINE
LA English
DT Article
DE posterior instability; allograft; posterior glenoid bone defect
ID SHOULDER INSTABILITY; HUMERAL HEAD; ALLOGRAFT RECONSTRUCTION; MCLAUGHLIN
PROCEDURE; SEGMENTAL DEFECTS; BLOCK PROCEDURE; DISLOCATION; OSTEOTOMY;
GLENOPLASTY; SUBLUXATION
AB When compared with anterior glenohumeral instability, posterior glenohumeral instability is a relatively rare condition, and it can pose a diagnostic and therapeutic challenge for the orthopaedic surgeon. Although many patients only have damage to the posterior capsulolabral structures, some have bone defects associated with posterior instability, including defects of the posterior glenoid rim, glenoid retroversion, and an anterosuperior impaction fracture of the humeral head known as the reverse Hill-Sachs lesion. When nonoperative treatments fail, surgical management aims to identify and address both soft tissue and bony factors involved in posterior instability so as to minimize the chances of recurrent instability after surgery. Operative treatment options vary for these different bone defects associated with posterior instability, and there are relatively little data to guide surgical indications and treatment decisions. In this article, we discuss our approach to the treatment of bone defects in posterior instability with emphasis on which techniques are used in different circumstances as well as technical pearls and pitfalls. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Cvetanovich, Gregory L.; Bhatia, Sanjeev; Cole, Brian J.] Rush Univ, Med Ctr, Div Sports Med, Dept Orthopaed Surg, Chicago, IL 60612 USA.
[Provencher, Matthew T.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Sports Med Serv, Boston, MA 02114 USA.
[Cole, Brian J.] Rush Univ, Med Ctr, Cartilage Restorat Ctr, Chicago, IL 60612 USA.
RP Cole, BJ (reprint author), Rush Univ, Med Ctr, Div Sports Med, Dept Orthopaed Surg, 1611 W Harrison,Suite 300, Chicago, IL 60612 USA.
EM bcole@rushortho.com
NR 45
TC 0
Z9 0
U1 0
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1060-1872
EI 1557-9794
J9 OPER TECHN SPORT MED
JI Oper. Tech. Sports Med.
PD MAR
PY 2014
VL 22
IS 1
BP 10
EP 17
DI 10.1053/j.otsm.2014.02.007
PG 8
WC Sport Sciences; Surgery
SC Sport Sciences; Surgery
GA AP5KZ
UT WOS:000342119400003
ER
PT J
AU Frank, RM
Golijanan, P
Gross, DJ
Provencher, MT
AF Frank, Rachel M.
Golijanan, Petar
Gross, Daniel J.
Provencher, Matthew T.
TI The Arthroscopic Rotator Interval Closure: Why, When, and How?
SO OPERATIVE TECHNIQUES IN SPORTS MEDICINE
LA English
DT Article
DE rotator interval; shoulder instability; arthroscopic closure; biceps
tendinopathy
ID MULTIDIRECTIONAL SHOULDER INSTABILITY; CORACOHUMERAL LIGAMENT; CUFF
INTERVAL; GLENOHUMERAL JOINT; POSTERIOR INSTABILITY; ALTERNATIVE
TECHNIQUE; ADHESIVE CAPSULITIS; MR ARTHROGRAPHY; LONG HEAD; ANTERIOR
AB The contribution of the rotator interval (RI) to the overall stability of the glenohumeral joint remains under debate. With improvements in the interpretation of both physical examination and diagnostic imaging findings, the diagnosis of RI pathology is becoming easier to identify. The clinical implications of RI pathology, however, still remain controversial. Injury to RI may contribute to glenohumeral instability, and both biomechanical and clinical studies have shown improvements in anterior shoulder stabilization following RI closure. The benefits of RI repair in the setting of posterior shoulder and multidirectional instability, however, are unclear. The optimal surgical technique is also unclear, and a variety of open and arthroscopic methods have been described. The purposes of this article are to review the surgical anatomy relevant to RI closure, discuss the biomechanical rationale for repairing the RI, and provide our preferred technique for performing arthroscopic RI closure. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Frank, Rachel M.] Rush Univ, Med Ctr, Dept Orthopaed Surg, Chicago, IL 60612 USA.
[Golijanan, Petar; Gross, Daniel J.; Provencher, Matthew T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Provencher, MT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 175 Cambridge St,Suite 400, Boston, MA 02114 USA.
EM mtprovencher@partners.org
NR 72
TC 1
Z9 1
U1 0
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 1060-1872
EI 1557-9794
J9 OPER TECHN SPORT MED
JI Oper. Tech. Sports Med.
PD MAR
PY 2014
VL 22
IS 1
BP 48
EP 57
DI 10.1053/j.otsm.2014.02.005
PG 10
WC Sport Sciences; Surgery
SC Sport Sciences; Surgery
GA AP5KZ
UT WOS:000342119400008
ER
PT J
AU Hayakawa, K
Pham, LDD
Arai, K
Lo, EH
AF Hayakawa, Kazuhide
Pham, Loc-Duyen D.
Arai, Ken
Lo, Eng H.
TI Reactive astrocytes promote adhesive interactions between brain
endothelium and endothelial progenitor cells via HMGB1 and beta-2
integrin signaling
SO STEM CELL RESEARCH
LA English
DT Article
ID GLYCATION END-PRODUCTS; GROUP BOX 1; CORTICAL ASTROCYTES;
ISCHEMIC-STROKE; RECEPTOR; RAGE; MICE; DIFFERENTIATION; ANGIOGENESIS;
AMPHOTERIN
AB Endothelial progenitor cells (EPCs) may contribute to neurovascular repair after stroke and neurodegeneration. A key step in this process should involve adhesive interactions between EPCs and the targeted cerebral endothelium. Here, we tested the hypothesis that reactive astrocytes may play a critical role in enhancing adhesive interactions and transmigration of EPCs across cerebral endothelial cells. Transiently seeding EPCs onto a monolayer of RBE. 4 rat brain endothelial cells resulted in a time-dependent adherence between the two cell types. Blocking beta 2 integrins on EPCs or blocking the receptor for advanced glycation endproducts (RAGE) on endothelial cells significantly decreased EPC-endothelial adherence. Next, we tested whether reactive astrocytes can enhance this process by growing EPCs, brain endothelial cells and astrocytes together in a transwell co-culture system. The presence of reactive astrocytes in the lower chamber significantly promoted adherence between EPCs and endothelial cells in the upper chamber. This process involved the release of soluble HMGB1 from reactive astrocytes that then upregulated endothelial expression of RAGE via Egr1 signaling. Directly adding HMGB1 to the transwell system also promoted EPC-endothelial adhesion and accelerated EPC transmigration into the lower chamber. These initial findings provide proof-of-concept that reactive astrocytes promote crosstalk between cerebral endothelium and EPCs. Further investigation of this phenomenon may lead to a better understanding of cell-cell interactions required for neurovascular recovery after stroke. (C) 2013 The Authors. Published by Elsevier B. V. All rights reserved.
C1 Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA USA.
Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA USA.
Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RP Hayakawa, K (reprint author), Neuroprotect Res Lab, MGH 149-2401,13th St, Charlestown, MA 02129 USA.
EM khayakawa1@partners.org; Lo@helix.mgh.harvard.edu
FU Rappaport Foundation; NIH [R01-NS76694, R01-NS65089, K99-NS80991]
FX Supported in part by Rappaport Foundation and NIH (R01-NS76694,
R01-NS65089, K99-NS80991).
NR 29
TC 9
Z9 12
U1 0
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1873-5061
EI 1876-7753
J9 STEM CELL RES
JI Stem Cell Res.
PD MAR
PY 2014
VL 12
IS 2
BP 531
EP 538
DI 10.1016/j.scr.2013.12.008
PG 8
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA AP7VU
UT WOS:000342286600017
PM 24480450
ER
PT J
AU Himle, MB
Capriotti, MR
Hayes, LP
Ramanujam, K
Scahill, L
Sukhodolsky, DG
Wilhelm, S
Deckersbach, T
Peterson, AL
Specht, MW
Walkup, JT
Chang, S
Piacentini, J
AF Himle, Michael B.
Capriotti, Matthew R.
Hayes, Loran P.
Ramanujam, Krishnapriya
Scahill, Lawrence
Sukhodolsky, Denis G.
Wilhelm, Sabine
Deckersbach, Thilo
Peterson, Alan L.
Specht, Matt W.
Walkup, John T.
Chang, Susanna
Piacentini, John
TI Variables Associated With Tic Exacerbation in Children With Chronic Tic
Disorders
SO BEHAVIOR MODIFICATION
LA English
DT Article
DE Tourette disorder; chronic tic disorder; Comprehensive Behavioral
Intervention for Tics; function-based assessment
ID TOURETTE-SYNDROME; DIFFERENTIAL REINFORCEMENT; FUNCTIONAL-ANALYSIS;
BEHAVIOR-THERAPY; SEVERITY-SCALE; SUPPRESSION; SYMPTOMS; RELIABILITY;
ADOLESCENTS; SCREEN
AB Research has shown that motor and vocal tics fluctuate in frequency, intensity, and form in response to environmental and contextual cues. Behavioral models have proposed that some of the variation in tics may reflect context-dependent interactive learning processes such that once tics are performed, they are influenced by environmental contingencies. The current study describes the results of a function-based assessment of tics (FBAT) from a recently completed study comparing Comprehensive Behavioral Intervention for Tics (CBIT) with supportive psychotherapy. The current study describes the frequency with which antecedent and consequence variables were reported to exacerbate tics and the relationships between these functional variables and sample baseline characteristics, comorbidities, and measures of tic severity. Results showed that tic-exacerbating antecedents and consequences were nearly ubiquitous in a sample of children with chronic tic disorder. In addition, functional variables were related to baseline measures of comorbid internalizing symptoms and specific measures of tic severity.
C1 [Himle, Michael B.] Univ Utah, Salt Lake City, UT 84112 USA.
[Hayes, Loran P.; Ramanujam, Krishnapriya] Univ Utah, Clin Psychol Program, Salt Lake City, UT 84112 USA.
[Capriotti, Matthew R.] Univ Wisconsin, Milwaukee, WI 53201 USA.
[Scahill, Lawrence] Emory Univ, Sch Med, Atlanta, GA USA.
[Scahill, Lawrence] Yale Univ, Sch Med, New Haven, CT USA.
[Sukhodolsky, Denis G.] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA.
[Wilhelm, Sabine] Massachusetts Gen Hosp, Related Disorders Program, Boston, MA 02114 USA.
[Deckersbach, Thilo] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA.
[Deckersbach, Thilo] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA.
[Wilhelm, Sabine; Deckersbach, Thilo] Harvard Univ, Sch Med, Boston, MA USA.
[Peterson, Alan L.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Specht, Matt W.; Walkup, John T.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
[Walkup, John T.] Weill Cornell Med Coll, Div Child & Adolescent Psychiat, New York, NY USA.
[Chang, Susanna; Piacentini, John] Univ Calif Los Angeles, Child OCD Anxiety & Tic Disorders Program, Los Angeles, CA USA.
RP Himle, MB (reprint author), Univ Utah, Dept Psychol, 380 S 1530 E,Rm 502, Salt Lake City, UT 84112 USA.
EM michael.himle@utah.edu
OI Scahill, Lawrence/0000-0001-5073-1707; Sukhodolsky,
Denis/0000-0002-5401-792X
FU NCRR NIH HHS [UL1 RR024139]; NIMH NIH HHS [R01 MH070802, R01MH070802]
NR 33
TC 6
Z9 6
U1 1
U2 6
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0145-4455
EI 1552-4167
J9 BEHAV MODIF
JI Behav. Modificat.
PD MAR
PY 2014
VL 38
IS 2
SI SI
BP 163
EP 183
DI 10.1177/0145445514531016
PG 21
WC Psychology, Clinical
SC Psychology
GA AN9SU
UT WOS:000340949700001
PM 24778433
ER
PT J
AU Garcia, HA
Finley, EP
Ketchum, N
Jakupcak, M
Dassori, A
Reyes, SC
AF Garcia, Hector A.
Finley, Erin P.
Ketchum, Norma
Jakupcak, Matthew
Dassori, Albana
Reyes, Stephanie C.
TI A Survey of Perceived Barriers and Attitudes Toward Mental Health Care
Among OEF/OIF Veterans at VA Outpatient Mental Health Clinics
SO MILITARY MEDICINE
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; COMBAT DEPLOYMENT; HELP-SEEKING; WAR
VETERANS; OIF VETERANS; IRAQ; AFGHANISTAN; MASCULINITY; THERAPY; PTSD
AB Objective: In an effort to improve our understanding of perceived treatment barriers among veterans of Operations Enduring Freedom and Iraqi Freedom (OEF/OIF) relative to other era veterans, the current study examined veteran attitudes and beliefs about mental health treatment and treatment-seeking, and perceived patient and institution-level logistical barriers to care. Method: A survey was conducted. among 434 Combat veterans seeking care in nine Veterans Affairs mental health care outpatient clinics. Results: When compared to Vietnam and Gulf War veterans, OEF/OIF veterans were significantly more likely to endorse negative treatment attitudes as possible barriers to care. OEF/OIF veterans were also more likely than Vietnam veterans to endorse conflicting work demands as a potential barrier, although this was the only logistical barrier for which OEF/OIF veterans' responses differed significantly from those of veterans of other eras. Among OEF/OIF veterans, older veterans were more likely than younger veterans to endorse barriers related to cost and time commitments. Conclusions: These findings suggest an important role for outreach and engagement strategies that address attitudinal barriers to treatment utilization among veteran populations.
C1 [Garcia, Hector A.; Finley, Erin P.; Dassori, Albana] South Texas Vet Hlth Care Syst, Mental Hlth Outpatient Serv, San Antonio, TX 78240 USA.
[Garcia, Hector A.; Finley, Erin P.; Dassori, Albana] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Finley, Erin P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
[Ketchum, Norma] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA.
[Jakupcak, Matthew] Puget Sound Hlth Care Syst, Deployment Hlth Clin S 116, Seattle, WA 98108 USA.
[Reyes, Stephanie C.] Univ Texas Hlth Sci Ctr San Antonio, PBRN Resource Ctr, Inst Integrat Med & Sci, San Antonio, TX 78229 USA.
RP Garcia, HA (reprint author), South Texas Vet Hlth Care Syst, Mental Hlth Outpatient Serv, 5788 Eckhert Rd 116A1, San Antonio, TX 78240 USA.
OI Finley, Erin/0000-0003-4497-7721
FU Institute for the Integration of Medicine and Science at the University
of Texas Health Science Center, San Antonio; National Institutes of
Health Clinical Translational Science Award (CTSA)
FX This project was supported by the Institute for the Integration of
Medicine and Science at the University of Texas Health Science Center,
San Antonio, and an National Institutes of Health Clinical Translational
Science Award (CTSA).
NR 28
TC 7
Z9 7
U1 1
U2 6
PU ASSOC MILITARY SURG US
PI BETHESDA
PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA
SN 0026-4075
EI 1930-613X
J9 MIL MED
JI Milit. Med.
PD MAR
PY 2014
VL 179
IS 3
BP 273
EP 278
DI 10.7205/MILMED-D-13-00076
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA AN7UJ
UT WOS:000340806200011
PM 24594461
ER
PT J
AU Murdoch, M
Polusny, MA
Street, A
Noorbaloochi, S
Simon, AB
Bangerter, A
Grill, J
Voller, E
AF Murdoch, Maureen
Polusny, Melissa A.
Street, Amy
Noorbaloochi, Siamak
Simon, Alisha B.
Bangerter, Ann
Grill, Joseph
Voller, Emily
TI Sexual Assault During the Time of Gulf War I: A Cross-Sectional Survey
of US Service Men Who Later Applied for Department of Veterans Affairs
PTSD Disability Benefits
SO MILITARY MEDICINE
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; POPULATION-BASED SURVEY; DEPLOYMENT
STRESSORS; PSYCHIATRIC-SYMPTOMS; NONRESPONSE BIAS; HARASSMENT; MILITARY;
WOMEN; ASSOCIATION; PREVALENCE
AB Objectives: To estimate the cumulative incidence of sexual assault during the time of Gulf War I among male Gulf War I Veterans who later applied for Department of Veterans Affairs (VA) post-traumatic stress disorder disability benefits and to identify potential risk and protective factors for sexual assault within the population. Method: Mailed, national, cross-sectional survey supplemented with VA administrative and clinical data. Results: Of 2,415 Veterans sampled, 1,700 (70%) responded. After adjusting for nonignorable missing data, the cumulative incidence of sexual assault during Gulf War I in this population ranged from 18% [95% confidence intervals (CI): 5.0%-51.9%] to 21% (95% CI: 20.0-22.0). Deployment was not associated with sexual assault [Odds Ratio (OR), 0.96; 95% CI: 0.75-1.23], but combat exposure was (OR, 1.80; 95% CI: 1.52-2.10). Other correlates of sexual assault within the population included working in a unit with greater tolerance of sexual harassment (OR, 1.80; 95% CI: 1.52-2.10) and being exposed to more sexual identity challenges (OR, 1.76; 95% CI: 1.55-2.00). Conclusions: The 9-month cumulative incidence of sexual assault in this particular population exceeded the lifetime cumulative incidence of sexual assault in U.S. civilian women. Although Persian Gulf deployment was not associated with sexual assault in this population, combat exposure was.
C1 [Murdoch, Maureen; Polusny, Melissa A.; Noorbaloochi, Siamak; Simon, Alisha B.; Bangerter, Ann; Grill, Joseph] Minneapolis VA Hlth Care Syst, VA Hlth Serv Res & Dev HSR&D Serv Ctr Excellence, Ctr Chron Dis Outcomes Res, Minneapolis, MN 55417 USA.
[Murdoch, Maureen] Minneapolis VA Hlth Care Syst, Gen Internal Med Sect, Minneapolis, MN 55417 USA.
[Murdoch, Maureen; Noorbaloochi, Siamak; Grill, Joseph] Univ Minnesota, Sch Med, Dept Internal Med, Minneapolis, MN 55455 USA.
[Polusny, Melissa A.; Voller, Emily] Minneapolis VA Hlth Care Syst, Dept Psychiat, Minneapolis, MN 55417 USA.
[Polusny, Melissa A.; Voller, Emily] Minneapolis VA Hlth Care Syst, Dept Psychol, Minneapolis, MN 55417 USA.
[Polusny, Melissa A.] Univ Minnesota, Sch Med, Dept Psychiat, Minneapolis, MN 55455 USA.
[Street, Amy] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA.
[Street, Amy] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA.
RP Murdoch, M (reprint author), Minneapolis VA Hlth Care Syst, VA Hlth Serv Res & Dev HSR&D Serv Ctr Excellence, Ctr Chron Dis Outcomes Res, One Vet Dr, Minneapolis, MN 55417 USA.
FU VA HSRD service [GWI 04-352]; VA Health Services Research and
Development Service Center of Excellence [HFP 98-001]
FX We thank Dr. Karen Kattar for her assistance working with study
participants. Tracking services were provided by the University of
Minnesota's Health Survey Research Center, under Dr. Eileen Harwood's
direction. This study was supported by grant no. GWI 04-352 from VA
HSR&D service and conducted at the Center for Chronic Disease Outcomes
Research, a VA Health Services Research and Development Service Center
of Excellence (Center grant no. HFP 98-001). Drs. Murdoch and Polusny
are core investigators, Ms. Bangerter is Senior Health Scientist, and
Dr. Noorbaloochi is statistician for the Center for Chronic Disease
Outcomes Research at the Minneapolis VA Medical Center.
NR 47
TC 7
Z9 7
U1 1
U2 8
PU ASSOC MILITARY SURG US
PI BETHESDA
PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA
SN 0026-4075
EI 1930-613X
J9 MIL MED
JI Milit. Med.
PD MAR
PY 2014
VL 179
IS 3
BP 285
EP 293
DI 10.7205/MILMED-D-12-00513
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA AN7UJ
UT WOS:000340806200013
PM 24594463
ER
PT J
AU Amara, J
Iverson, KM
Krengel, M
Pogoda, TK
Hendricks, A
AF Amara, Jomana
Iverson, Katherine M.
Krengel, Maxine
Pogoda, Terri K.
Hendricks, Ann
TI Anticipating the Traumatic Brain Injury-Related Health Care Needs of
Women Veterans After the Department of Defense Change in Combat
Assignment Policy
SO WOMENS HEALTH ISSUES
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; IRAQI FREEDOM; MILITARY; GENDER
AB Background: Female service members' presence in combat zones during Operation Enduring Freedom and Operation Iraqi Freedom is unprecedented both in terms of the number of women deployed and the nature of their involvement. In light of changing Department of Defense policy governing the deployment of women in combat zones, this article intends to set the groundwork for estimating future combat-related injuries and subsequent Veterans Health Administration (VHA) utilization while focusing on traumatic brain injury (TBI).
Methods: The article summarizes and presents the results of a study that examines veterans who present to VHA for TBI evaluation. For a national sample of veterans, a dataset including information on post-screening utilization, diagnoses, and location of care was constructed. The dataset included self-reported health symptoms and other information obtained from a standardized national VHA post-screening clinical evaluation, the comprehensive TBI evaluation (CTBIE).
Findings: Both women and men utilize high levels of VHA health care after a CTBIE. However, there are gender differences in the volume and types of services used, with women utilizing different services than their male counterparts and incurring higher costs, including higher overall and outpatient costs.
Conclusion: As women veterans seek more of their health care from the VHA, there will be a need for more coordinated care to identify and manage deployment-related TBI and common comorbidities such as posttraumatic stress disorder, depression, and chronic pain. Deployment-connected injuries are likely to rise because of the rescinding of the ban on women in combat. This in turn has critical implications for VHA strategic planning and budgeting. Published by Elsevier Inc.
C1 [Amara, Jomana] Naval Postgrad Sch, DRMI, Monterey, CA 93943 USA.
[Iverson, Katherine M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA.
[Iverson, Katherine M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA.
[Krengel, Maxine] VA Boston Healthcare Syst, Boston, MA USA.
[Krengel, Maxine] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Pogoda, Terri K.] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA USA.
[Pogoda, Terri K.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA.
[Hendricks, Ann] VA Boston Healthcare Syst, Hlth Care Financing & Econ Ctr, Boston, MA USA.
RP Amara, J (reprint author), Naval Postgrad Sch, DRMI Code 64, 699 Dyer Rd,Bldg 234, Monterey, CA 93943 USA.
EM jhamara@nps.edu
NR 37
TC 4
Z9 4
U1 3
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1049-3867
EI 1878-4321
J9 WOMEN HEALTH ISS
JI Womens Health Iss.
PD MAR-APR
PY 2014
VL 24
IS 2
BP E171
EP E176
DI 10.1016/j.whi.2013.12.004
PG 6
WC Public, Environmental & Occupational Health; Women's Studies
SC Public, Environmental & Occupational Health; Women's Studies
GA AO1ZG
UT WOS:000341113500003
PM 24630421
ER
PT J
AU Gunn, CM
Freund, KM
Kaplan, SA
Raj, A
Carr, PL
AF Gunn, Christine M.
Freund, Karen M.
Kaplan, Samantha A.
Raj, Anita
Carr, Phyllis L.
TI Knowledge and Perceptions of Family Leave Policies Among Female Faculty
in Academic Medicine
SO WOMENS HEALTH ISSUES
LA English
DT Article
ID CAREER SATISFACTION; WOMEN PHYSICIANS; GENDER; SCHOOL; FLEXIBILITY
AB Objective: The purpose of this research was to examine the knowledge and perceptions of family leave policies and practices among senior leaders including American Association of Medical College members of the Group on Women in Medicine and Science (GWIMS) to identify perceived barriers to career success and satisfaction among female faculty.
Methods: In 2011 and 2012, GWIMS representatives and senior leaders at 24 medical schools were invited to participate in an interview about faculty perceptions of gender equity and overall institutional climate. An inductive, thematic analysis of the qualitative data was conducted to identify themes represented in participant responses. The research team read and reviewed institutional family leave policies for concordance with key informant descriptions.
Findings: There were 22 GWIMS representatives and senior leaders in the final sample. Participants were all female; 18 (82%) were full professors with the remainder being associate professors. Compared with publicly available policies at each institution, the knowledge of nine participants was consistent with policies, was discrepant for six, with the remaining seven acknowledging a lack of knowledge of policies. Four major themes were identified from the interview data: 1) Framing family leave as a personal issue undermines its effect on female faculty success; 2) poor communication of policies impairs access and affects organizational climate; 3) discrepancies in leave implementation disadvantage certain faculty in terms of time and pay; and 4) leave policies are valued and directly related to academic productivity.
Conclusions: Family leave policies are an important aspect of faculty satisfaction and academic success, yet policy awareness among senior leaders is lacking. Further organizational support is needed to promote equitable policy creation and implementation to support women in medical academia. Copyright (C) 2014 by the Jacobs Institute of Women's Health. Published by Elsevier Inc.
C1 [Gunn, Christine M.] Boston Univ, Sch Med, Dept Med, Womens Hlth Unit, Boston, MA 02118 USA.
[Freund, Karen M.] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA.
[Kaplan, Samantha A.] Boston Univ, Sch Med, Dept Obstet & Gynecol, Boston, MA 02118 USA.
[Raj, Anita] Univ Calif San Diego, Dept Med, Div Global Publ Hlth, La Jolla, CA 92093 USA.
[Carr, Phyllis L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
RP Gunn, CM (reprint author), Boston Univ, Sch Med, Dept Med, Womens Hlth Unit, 801 Massachusetts Ave,1st Floor, Boston, MA 02118 USA.
EM cgunn@bu.edu
OI Freund, Karen/0000-0002-9049-5574; Gunn, Christine/0000-0003-3340-2834
FU NIGMS NIH HHS [5R01 GM088470-02, R01 GM088470]
NR 26
TC 5
Z9 5
U1 1
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1049-3867
EI 1878-4321
J9 WOMEN HEALTH ISS
JI Womens Health Iss.
PD MAR-APR
PY 2014
VL 24
IS 2
BP E205
EP E210
DI 10.1016/j.whi.2013.12.008
PG 6
WC Public, Environmental & Occupational Health; Women's Studies
SC Public, Environmental & Occupational Health; Women's Studies
GA AO1ZG
UT WOS:000341113500007
PM 24533979
ER
PT J
AU Kazerooni, R
Vu, K
Takizawa, A
Broadhead, C
Morreale, AP
AF Kazerooni, Rashid
Khanh Vu
Takizawa, Atsuhiko
Broadhead, Christine
Morreale, Anthony P.
TI Association of Copayment and Socioeconomic Status with Hormonal
Contraceptive Adherence in a Female Veteran Population
SO WOMENS HEALTH ISSUES
LA English
DT Article
ID AFFORDABLE CARE ACT; UNINTENDED PREGNANCY; UNITED-STATES; LOW-INCOME;
DISPARITIES; EXPERIENCES; PREDICTORS; OUTCOMES; POVERTY; WOMEN
AB Background: There are limited studies available analyzing association between copayment and hormonal contraception adherence. The study was conducted to investigate the association between copayment status and hormonal contraceptive adherence in a female veteran population when stratified by socioeconomic status.
Methods: This 4-year, retrospective, cohort study of women Veterans from the Veterans Integrated Service Network 22, a network of Veterans Affairs facilities that includes Southern California and Nevada, included patients who received a new hormonal contraceptive prescription between October 1, 2008, and September 30, 2012. Patients were split into five quintiles (one having the lowest income and five the highest) dependent on zip code-based median annual household income from the 2007-2011 American Community Survey data. Medication possession ratio difference of copayment versus no copayment group for each respective quintile was the primary outcome. Analysis was done using multiple linear regression models.
Results: A total of 3,622 patients met the inclusion criteria and were included in the analysis. Over the entire population, copayment was significantly associated with reduced adherence (-0.034; 95% confidence interval [CI], -0.06 to -0.008). Patients in the highest socioeconomic group, quintile five, had the largest reduction in adherence associated with having a copayment (-0.073; 95% CI, -0.129 to -0.017). Patients in the other four quintiles saw varying levels of decreased adherence respectively, although the differences did not achieve statistical significance.
Conclusion: The association between adherence and copayment status varied by socioeconomic status. Our findings suggest that even affluent patients may be discouraged from adherence when subject to a copayment. If larger studies substantiate these findings, consideration should be given to a policy that exempts women veterans from copayments for hormonal contraceptives. Published by Elsevier Inc.
C1 [Kazerooni, Rashid; Khanh Vu; Takizawa, Atsuhiko] Vet Affairs San Diego Healthcare Syst, San Diego, CA 92161 USA.
[Kazerooni, Rashid; Khanh Vu; Takizawa, Atsuhiko] UCSD Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA USA.
[Broadhead, Christine] Sharp HealthCare, San Diego, CA USA.
[Morreale, Anthony P.] US Dept Vet Affairs, Natl Pharm Benefits Management Serv, San Diego, CA USA.
RP Kazerooni, R (reprint author), Vet Affairs San Diego Healthcare Syst, 3350 La Jolla Village Dr 119, San Diego, CA 92161 USA.
EM rashid.kazerooni@va.gov
OI Kazerooni, Rashid/0000-0003-3223-2597
NR 28
TC 2
Z9 2
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1049-3867
EI 1878-4321
J9 WOMEN HEALTH ISS
JI Womens Health Iss.
PD MAR-APR
PY 2014
VL 24
IS 2
BP E237
EP E241
DI 10.1016/j.whi.2013.12.002
PG 5
WC Public, Environmental & Occupational Health; Women's Studies
SC Public, Environmental & Occupational Health; Women's Studies
GA AO1ZG
UT WOS:000341113500011
PM 24533983
ER
PT J
AU Robison, K
Clark, L
Eng, W
Wu, L
Raker, C
Clark, M
Tejada-Berges, T
Dizon, DS
AF Robison, Katina
Clark, Lindsay
Eng, Whitney
Wu, Lily
Raker, Christina
Clark, Melissa
Tejada-Berges, Trevor
Dizon, Don S.
TI Cervical Cancer Prevention: Asian-American Women's Knowledge and
Participation in Screening Practices
SO WOMENS HEALTH ISSUES
LA English
DT Article
ID HUMAN-PAPILLOMAVIRUS VACCINE; UNITED-STATES
AB Objective: The purpose of this study was to compare cervical cancer knowledge and prevention strategy participation among Chinese-American women compared with Southeast-Asian-American women.
Methods: We performed a cross-sectional survey of Chinese and Southeast Asian women in Rhode Island. Anonymous surveys were administered following informed consent. The survey included demographics and questions related to health care practices, cervical cancer, and the human papilloma virus (HPV). Categorical variables were compared by Fisher's exact test. Mean scores of correct answers on the knowledge questions were compared by Student's t-test and analysis of variance.
Results: Ninety-six Chinese women and 132 Southeast Asian women were included in the analysis. Sixty-seven percent of Chinese women had at least a college education compared with 37% of Southeast Asian women (p < .0001). Nineteen percent of Chinese women reported annual household incomes of greater than $100,000 compared with 3% of Southeast Asian women (p = .0003). Twenty percent of Southeast Asian women did not have health insurance compared with 10% of Chinese women (p = .06). Among both groups, 25% of participants either never had a pap test or did not know if they ever had a pap test. There was a greater lack of knowledge about the relationship between HPV and cervical cancer among Chinese (mean 2.9 out of 8 questions) compared with Southeast Asian (mean 3.6 out of 8 questions; p = .02).
Conclusions: Regardless of ethnic subgroup, education, or income, all participants had a poor knowledge of cervical cancer and HPV. This study supports the need for improvement in cervical cancer prevention education among all Asian women. Copyright (C) 2014 by the Jacobs Institute of Women's Health. Published by Elsevier Inc.
C1 [Robison, Katina; Clark, Lindsay; Eng, Whitney; Wu, Lily; Raker, Christina; Clark, Melissa; Tejada-Berges, Trevor] Brown Univ, Women & Infants Hosp Rhode Isl, Warren Alpert Med Sch, Providence, RI 02905 USA.
[Dizon, Don S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
RP Robison, K (reprint author), Brown Univ, Women & Infants Hosp, Program Womens Oncol, 101 Dudley St, Providence, RI 02905 USA.
EM krobison@wihri.org
FU NICHD NIH HHS [K12HD050108]
NR 15
TC 6
Z9 6
U1 1
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1049-3867
EI 1878-4321
J9 WOMEN HEALTH ISS
JI Womens Health Iss.
PD MAR-APR
PY 2014
VL 24
IS 2
BP E231
EP E236
DI 10.1016/j.whi.2013.12.005
PG 6
WC Public, Environmental & Occupational Health; Women's Studies
SC Public, Environmental & Occupational Health; Women's Studies
GA AO1ZG
UT WOS:000341113500010
PM 24533982
ER
PT J
AU Arias, DAA
Kim, HJ
Zhou, P
Holderried, TAW
Wang, X
Dranoff, G
Cantor, H
AF Arias, Diana A. Alvarez
Kim, Hye-Jung
Zhou, Penghui
Holderried, Tobias A. W.
Wang, Xuan
Dranoff, Glenn
Cantor, Harvey
TI Disruption of CD8(+) Treg Activity Results in Expansion of T Follicular
Helper Cells and Enhanced Antitumor Immunity
SO CANCER IMMUNOLOGY RESEARCH
LA English
DT Article
ID MONOCLONAL-ANTIBODY; AUTOIMMUNE-DISEASE; DENDRITIC CELLS;
SELF-TOLERANCE; SYSTEMIC-LUPUS; TUMOR-CELLS; PHASE-II; CANCER;
IMMUNOTHERAPY; RESPONSES
AB Tumor growth is associated with the inhibition of host antitumor immune responses that can impose serious obstacles to cancer immunotherapy. To define the potential contribution of Qa-1-restricted CD8 regulatory T cells (Treg) to the development of tumor immunity, we studied B6.Qa-1 D227K mice that harbor a point mutation in the MHC class Ib molecule Qa-1 that impairs CD8 Treg suppressive activity. Here, we report that the growth of B16 melanoma is substantially delayed in these Qa-1-mutant mice after therapeutic immunization with B16 melanoma cells engineered to express granulocyte macrophage colony-stimulating factor compared with Qa-1 B6-WT controls. Reduced tumor growth is associated with enhanced expansion of follicular T helper cells, germinal center B cells, and high titers of antitumor autoantibodies, which provoke robust antitumor immune responses in concert with tumor-specific cytolytic T cells. Analysis of tumor-infiltrating T cells revealed that the Qa-1 DK mutation was associated with an increase in the ratio of CD8(+) T effectors compared with CD8 Tregs. These data suggest that the CD8(+) T effector-Treg ratio may provide a useful prognostic index for cancer development and raise the possibility that depletion or inactivation of CD8 Tregs represents a potentially effective strategy to enhance antitumor immunity. (C) 2013 AACR.
C1 [Arias, Diana A. Alvarez; Kim, Hye-Jung; Zhou, Penghui; Holderried, Tobias A. W.; Wang, Xuan; Dranoff, Glenn; Cantor, Harvey] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Dranoff, Glenn] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Arias, Diana A. Alvarez; Kim, Hye-Jung; Zhou, Penghui; Holderried, Tobias A. W.; Cantor, Harvey] Harvard Univ, Dept Microbiol & Immunol, Div Immunol, Sch Med, Boston, MA 02115 USA.
[Dranoff, Glenn] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Holderried, Tobias A. W.] Univ Dusseldorf, Dept Gastroenterol Hepatol & Infect Dis, Dusseldorf, Germany.
RP Cantor, H (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.
EM harvey_cantor@dfci.harvard.edu
FU NIH [AI 037562]; NRSA [T32AI07386, T32CA070083]; University of
Dusseldorf (Dusseldorf, Germany)
FX This work was supported in part by NIH research grant AI 037562 and a
gift from the LeRoy Schecter Research Foundation (to H. Cantor) and NRSA
Fellowships (T32AI07386; to D. Alvarez Arias) and (T32CA070083; to H-J.
Kim). T.A.W. Holderried is supported by the University of Dusseldorf
(Dusseldorf, Germany).
NR 38
TC 6
Z9 6
U1 0
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 MAR
PY 2014
VL 2
IS 3
BP 207
EP 216
DI 10.1158/2326-6066.CIR-13-0121
PG 10
WC Oncology; Immunology
SC Oncology; Immunology
GA AM7GH
UT WOS:000340032800004
ER
PT J
AU Bachireddy, P
Wu, CJ
AF Bachireddy, Pavan
Wu, Catherine J.
TI Understanding anti-leukemia responses to donor lymphocyte infusion
SO ONCOIMMUNOLOGY
LA English
DT Editorial Material
DE T cell exhaustion; donor lymphocyte infusion; CML; stem cell
transplantation; tumor-infiltrating lymphocytes
ID STEM-CELL TRANSPLANTATION; LEUKEMIA; EXHAUSTION; IMMUNITY
AB Donor lymphocyte infusion (DLI) is an established and potentially curative immune therapy for relapsed leukemia after hematopoietic stem cell transplant (HSCT). Herein, we describe the utility of DLI as a tractable model system to glean fresh insights into understanding and predicting effective anti-leukemia immunity.
C1 [Wu, Catherine J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA.
Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.
RP Wu, CJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM cwu@partners.org
FU NCI NIH HHS [T32 CA009172]
NR 10
TC 2
Z9 3
U1 0
U2 1
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 2162-4011
EI 2162-402X
J9 ONCOIMMUNOLOGY
JI OncoImmunology
PD MAR
PY 2014
VL 3
IS 3
AR e28187
DI 10.4161/onci.28187
PG 3
WC Oncology; Immunology
SC Oncology; Immunology
GA AM6EC
UT WOS:000339954400006
PM 25340010
ER
PT J
AU Naritoku, WY
Alexander, CB
Bennett, BD
Black-Schaffer, WS
Brissette, MD
Grimes, MM
Hoffman, RD
Hunt, JL
Iezzoni, JC
Johnson, R
Kozel, J
Mendoza, RM
Post, MD
Powell, SZ
Procop, GW
Steinberg, JJ
Thorsen, LM
Nestler, SP
AF Naritoku, Wesley Y.
Alexander, C. Bruce
Bennett, Betsy D.
Black-Schaffer, W. Stephen
Brissette, Mark D.
Grimes, Margaret M.
Hoffman, Robert D.
Hunt, Jennifer L.
Iezzoni, Julia C.
Johnson, Rebecca
Kozel, Jessica
Mendoza, Ricardo M.
Post, Miriam D.
Powell, Suzanne Z.
Procop, Gary W.
Steinberg, Jacob J.
Thorsen, Linda M.
Nestler, Steven P.
TI The Pathology Milestones and the Next Accreditation System
SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
LA English
DT Article
AB Context.-In the late 1990s, the Accreditation Council for Graduate Medical Education developed the Outcomes Project and the 6 general competencies with the intent to improve the outcome of graduate medical education in the United States. The competencies were used as the basis for developing learning goals and objectives and tools to evaluate residents' performance. By the mid-2000s the stakeholders in resident education and the general public felt that the Outcomes Project had fallen short of expectations.
Objective.-To develop a new evaluation method to track trainee progress throughout residency using bench-marks called milestones. A change in leadership at the Accreditation Council for Graduate Medical Education brought a new vision for the accreditation of training programs and a radically different approach to the evaluation of residents.
Data Sources.-The Pathology Milestones Working Group reviewed examples of developing milestones in other specialties, the literature, and the Accreditation Council for Graduate Medical Education program requirements for pathology to develop pathology milestones. The pathology milestones are a set of objective descriptors for measuring progress in the development of competency in patient care, procedural skill sets, medical knowledge, practice-based learning and improvement, interpersonal and communication skills, professionalism, and systems-based practice.
Conclusions.-The milestones provide a national standard for evaluation that will be used for the assessment of all residents in Accreditation Council for Graduate Medical Education-accredited pathology training programs.
C1 [Naritoku, Wesley Y.] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA.
[Alexander, C. Bruce] Univ Alabama, Dept Pathol, Tuscaloosa, AL 35487 USA.
[Bennett, Betsy D.; Johnson, Rebecca] Amer Board Pathol, Tampa, FL USA.
[Black-Schaffer, W. Stephen] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Black-Schaffer, W. Stephen] Harvard Univ, Sch Med, Boston, MA USA.
[Brissette, Mark D.] Joint Pathol Ctr, Hematopathol Div, Silver Spring, MD USA.
[Brissette, Mark D.] Joint Pathol Ctr, Hematopathol Div, Washington, DC USA.
[Grimes, Margaret M.] Virginia Commonwealth Univ, Dept Pathol, Med Ctr, Richmond, VA 23284 USA.
[Hoffman, Robert D.] Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Nashville, TN USA.
[Hunt, Jennifer L.] Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA.
[Iezzoni, Julia C.] Univ Virginia Hlth Syst, Dept Pathol, Charlottesville, VA USA.
[Kozel, Jessica] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA.
[Mendoza, Ricardo M.] E Carolina Univ, Dept Pathol, Greenville, NC USA.
[Post, Miriam D.] Univ Colorado, Sch Med, Dept Pathol, Aurora, CO USA.
[Powell, Suzanne Z.] Methodist Hosp, Dept Pathol & Genom Med, Houston, TX 77030 USA.
[Procop, Gary W.] Cleveland Clin Fdn, Dept Mol Pathol, Pathol & Lab Med Inst, Cleveland, OH 44195 USA.
[Steinberg, Jacob J.] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA.
[Thorsen, Linda M.; Nestler, Steven P.] Accreditat Council Grad Med Educ, Chicago, IL USA.
RP Naritoku, WY (reprint author), Univ So Calif, Keck Sch Med, Dept Pathol, 1200 N State St,Clin Tower Room A7A119, Los Angeles, CA 90033 USA.
EM naritoku@usc.edu
NR 10
TC 9
Z9 9
U1 0
U2 6
PU COLL AMER PATHOLOGISTS
PI NORTHFIELD
PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA
SN 0003-9985
EI 1543-2165
J9 ARCH PATHOL LAB MED
JI Arch. Pathol. Lab. Med.
PD MAR
PY 2014
VL 138
IS 3
BP 307
EP 315
DI 10.5858/arpa.2013-0260-SA
PG 9
WC Medical Laboratory Technology; Medicine, Research & Experimental;
Pathology
SC Medical Laboratory Technology; Research & Experimental Medicine;
Pathology
GA AM0QI
UT WOS:000339550300006
PM 24576024
ER
PT J
AU McQuitty, E
Zhang, W
Hendrickson, H
Tio, FO
Jagirdar, J
Olsen, R
Cagle, PT
AF McQuitty, Elizabeth
Zhang, Wei
Hendrickson, Heather
Tio, Fermin O.
Jagirdar, Jaishree
Olsen, Randall
Cagle, Philip T.
TI Lung Adenocarcinoma Biomarker Incidence in Hispanic Versus Non-Hispanic
White Patients
SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
LA English
DT Article
ID CANCER PATIENTS; KRAS MUTATIONS; PIK3CA MUTATION; GENE; EGFR; FREQUENCY;
SURVIVAL; FEATURES; THERAPY
AB Context.-Lung cancer is the leading cause of cancer deaths in the United States and worldwide. Biomarker testing is critical to personalized therapy in lung adenocarcinoma and has been extensively investigated in non-Hispanic whites, Asians, and African Americans. However, little information addresses the underlying genetic changes in lung adenocarcinoma among Hispanic patients in the United States.
Objective.-To identify targetable biomarkers other than EGFR and EML4-ALK in Hispanic patients with lung adenocarcinoma.
Design.-We tested DNA extracted from 85 lung adenocarcinoma specimens collected from 40 Hispanic and 43 non-Hispanic white patients for previously reported mutations in KRAS, MET, BRAF, mTOR, STAT3, JAK2, PIK3CA, AKT1 through AKT3, and PTEN with a custom Sequenom massARRAY assay (Sequenom, San Diego, California).
Results.-Mutations in KRAS were identified in 11 cases (13%; 6 Hispanic [7%], 5 non-Hispanic white [6%]) and had no correlation with sex, age, or smoking history. Mutations in PIK3CA were identified in 2 of the 40 Hispanic patients (5%), including one patient (2.5%) with a concurrent KRAS mutation. The tumors were wild type for all other genes tested.
Conclusions.-Targetable biomarkers other than EGFR and EML4-ALK were identified in 7 of the 40 Hispanic patients (18%) and 5 of the 43 non-Hispanic white patients (12%), suggesting a similar mutational frequency. Our highly multiplexed genotyping assay detected actionable mutations in 14% (12 of 83) more patients than would have been identified by EGFR and EML4-ALK testing alone.
C1 [Zhang, Wei; Jagirdar, Jaishree] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA.
[Tio, Fermin O.] South Texas Vet Hlth Care Syst, Dept Anat & Clin Pathol, San Antonio, TX USA.
[McQuitty, Elizabeth; Hendrickson, Heather; Olsen, Randall; Cagle, Philip T.] Houston Methodist Hosp, Dept Pathol & Genom Med, Houston, TX 77030 USA.
RP Cagle, PT (reprint author), Houston Methodist Hosp, Dept Pathol & Genom Med, 6565 Fannin St,M227, Houston, TX 77030 USA.
EM pcagle@HoustonMethodist.org
NR 30
TC 3
Z9 3
U1 2
U2 5
PU COLL AMER PATHOLOGISTS
PI NORTHFIELD
PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA
SN 0003-9985
EI 1543-2165
J9 ARCH PATHOL LAB MED
JI Arch. Pathol. Lab. Med.
PD MAR
PY 2014
VL 138
IS 3
BP 390
EP 394
DI 10.5858/arpa.2013-0225-OA
PG 5
WC Medical Laboratory Technology; Medicine, Research & Experimental;
Pathology
SC Medical Laboratory Technology; Research & Experimental Medicine;
Pathology
GA AM0QI
UT WOS:000339550300017
PM 23802852
ER
PT J
AU O'Neil, ME
Carlson, KF
Storzbach, D
Brenner, LA
Freeman, M
Quinones, AR
Motu'apuaka, M
Kansagara, D
AF O'Neil, Maya E.
Carlson, Kathleen F.
Storzbach, Daniel
Brenner, Lisa A.
Freeman, Michele
Quinones, Ana R.
Motu'apuaka, Makalapua
Kansagara, Devan
TI Factors Associated with Mild Traumatic Brain Injury in Veterans and
Military Personnel: A Systematic Review
SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY
LA English
DT Review
DE Mild traumatic brain injury; Veteran; Military; Systematic review;
Combat deployment; Cognitive functioning; Deployment related conditions
ID POSTTRAUMATIC-STRESS-DISORDER; SERVICE MEMBERS; NEUROPSYCHOLOGICAL
PERFORMANCE; POSTCONCUSSIVE SYMPTOMS; OEF/OIF VETERANS; OIF/OEF
VETERANS; WAR VETERANS; US SOLDIERS; COMBAT; BLAST
AB A history of mild traumatic brain injury (mTBI) is common among military members who served in Operations Enduring Freedom, Iraqi Freedom, and New Dawn (OEF/OIF/OND). We completed a systematic review to describe the cognitive, mental health, physical health, functional, social, and cost consequences of mTBI in Veteran and military personnel. Of 2668 reviewed abstracts, the 31 included studies provided very low strength evidence for the questions of interest. Cognitive, physical, and mental health symptoms were commonly reported by Veterans/military members with a history of mTBI. On average, these symptoms were not significantly more common in those with a history of mTBI than in those without, although a lack of significant mean differences does not preclude the possibility that some individuals could experience substantial effects related to mTBI history. Evidence of potential risk or protective factors moderating mTBI outcomes was unclear. Although the overall strength of evidence is very low due to methodological limitations of included studies, our findings are consistent with civilian studies. Appropriate re-integration services are needed to address common comorbid conditions, such as treatment for post-traumatic stress disorder, substance use disorders, headaches, and other difficulties that Veterans and members of the military may experience after deployment regardless of mTBI history.
C1 [O'Neil, Maya E.; Carlson, Kathleen F.; Storzbach, Daniel; Freeman, Michele; Quinones, Ana R.; Motu'apuaka, Makalapua; Kansagara, Devan] Portland VA Med Ctr, Portland, OR USA.
[O'Neil, Maya E.; Carlson, Kathleen F.; Storzbach, Daniel; Freeman, Michele; Kansagara, Devan] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Brenner, Lisa A.] VISN 19 MIRECC, Denver VA Med Ctr, Denver, CO USA.
[Brenner, Lisa A.] Univ Colorado, Denver, CO 80202 USA.
RP O'Neil, ME (reprint author), 3710 SW US Vet Hosp Rd,Mail Code R&D 71, Portland, OR 97239 USA.
EM maya.oneil@va.gov
FU Veterans Affairs Quality Enhancement Research Initiative (QUERI)
Evidence-based Synthesis Program (ESP)
FX This study was funded by the Veterans Affairs Quality Enhancement
Research Initiative (QUERI) Evidence-based Synthesis Program (ESP). The
views expressed in this article are those of the authors and do not
necessarily represent the views of the Department of Veterans Affairs.
All authors declare no conflicts of interests involved in the research
presented in the manuscript. The corresponding author (MEO) declares she
had full access to all the data in the study and takes responsibility
for the integrity of the data and the accuracy of the data analysis. We
thank Edwin Reid and Tomiye Akagi for their editorial assistance, and
Rose Relevo for library assistance.
NR 40
TC 10
Z9 10
U1 1
U2 15
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1355-6177
EI 1469-7661
J9 J INT NEUROPSYCH SOC
JI J. Int. Neuropsychol. Soc.
PD MAR
PY 2014
VL 20
IS 3
BP 249
EP 261
DI 10.1017/S135561771300146X
PG 13
WC Clinical Neurology; Neurosciences; Psychiatry; Psychology
SC Neurosciences & Neurology; Psychiatry; Psychology
GA AM0UG
UT WOS:000339561800001
PM 24622505
ER
PT J
AU Gellad, WF
Choi, P
Mizah, M
Good, CB
Kesselheim, AS
AF Gellad, Walid F.
Choi, Phillip
Mizah, Margaret
Good, Chester B.
Kesselheim, Aaron S.
TI Assessing the Chiral Switch: Approval and Use of Single-Enantiomer
Drugs, 2001 to 2011
SO AMERICAN JOURNAL OF MANAGED CARE
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; 8-WEEK COMPARATIVE TRIAL; EROSIVE
ESOPHAGITIS; DOUBLE-BLIND; OMEPRAZOLE; COST; MULTICENTER; MEDICATION;
HEALTH; NAMES
AB Objectives: A "chiral switch" occurs in the pharmaceutical market when a drug made up of 2 enantiomer forms is replaced with a purified single-enantiomer version, often in the context of a patent expiration.We studied the prevalence of chiral switching in the United States over the past decade, including trends in use of, and expenditures on, these products in Medicaid.
Study Design: Retrospective analysis.
Methods: We used US Adopted Names prefixes (lev/levo/ar/es/dex/dextro) to identify all single-enantiomer drugs approved from 2001 to 2011. From publicly available US Food and Drug Administration (FDA) approval documents, we extracted the characteristics of the pivotal premarket trials for the single enantiomers. Specifically, we evaluated whether the single enantiomer was directly compared with the precursor racemic drug and whether there was evidence of superior efficacy. We used quarterly drug expenditure data from each state Medicaid program to chart trends in use of, and spending on, the single-enantiomer products and their racemic precursors during the study period.
Results: From 2001 to 2011, the FDA approved 9 single-enantiomer products: dexlansoprazole, levoleucovorin, levocetirizine, armodafinil, arformoterol, eszopiclone, escitalopram, dexmethyl-phenidate, and esomeprazole. Of those 9 drugs, 3 had at least 1 pre-approval randomized trial that included the racemic precursor as a direct comparator, but there was no evidence of superiority of the single enantiomer over the racemic at comparable doses. Between 2001 and 2011, US Medicaid programs spent approximately $6.3 billion on these 9 single-enantiomer drugs.
Conclusions: Recently approved single-enantiomer drugs showed no evidence of superior efficacy over the older racemic precursors in the pivotal trials leading to their approval, and in a majority of cases, they were not directly compared.
C1 [Gellad, Walid F.; Mizah, Margaret; Good, Chester B.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15206 USA.
[Gellad, Walid F.; Choi, Phillip; Good, Chester B.] Univ Pittsburgh, Dept Med, Santa Monica, CA USA.
[Kesselheim, Aaron S.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Program Regulat Therapeut & Law PORTAL, Boston, MA 02115 USA.
[Kesselheim, Aaron S.] Harvard Univ, Sch Med, Boston, MA USA.
RP Gellad, WF (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, 7180 Highland Dr, Pittsburgh, PA 15206 USA.
EM walid.gellad@va.gov
FU VA Health Services Research & Development (HSR&D) career development
award [CDA 09-207]; Harvard Program in Therapeutic Science, Greenwall
Faculty Scholarship in Bioethics; Agency for Healthcare Research Quality
[K08HS18465-01]; Robert Wood Johnson Foundation Investigator Award in
Health Policy Research
FX Dr Gellad is supported by a VA Health Services Research & Development
(HSR&D) career development award (CDA 09-207). Dr Kesselheim is
supported by the Harvard Program in Therapeutic Science, Greenwall
Faculty Scholarship in Bioethics, a career development award from the
Agency for Healthcare Research & Quality (K08HS18465-01) and a Robert
Wood Johnson Foundation Investigator Award in Health Policy Research.
None of the funders played any role in the preparation of this article.
NR 44
TC 4
Z9 4
U1 3
U2 20
PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC
PI PLAINSBORO
PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA
SN 1088-0224
J9 AM J MANAG CARE
JI Am. J. Manag. Care
PD MAR
PY 2014
VL 20
IS 3
BP E90
EP E97
PG 8
WC Health Care Sciences & Services; Health Policy & Services; Medicine,
General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA AL5AO
UT WOS:000339146100006
PM 24773330
ER
PT J
AU Nutt, JG
Siderowf, AD
Guttman, M
Schmidt, PN
Zamudio, JI
Wu, SS
Okun, MS
Simuni, T
Parashos, FSA
Dahodwala, NA
Davis, TL
Giladi, N
Gurevich, T
Hauser, RA
Jankovic, J
Lyons, KE
Marsh, L
Miyasaki, JM
Morgan, JC
Santiago, AJ
Tarsy, D
Mari, Z
Malaty, IA
Nelson, EC
AF Nutt, J. G.
Siderowf, A. D.
Guttman, M.
Schmidt, P. N.
Zamudio, J. I.
Wu, S. S.
Okun, M. S.
Simuni, T.
Parashos, F. S. A.
Dahodwala, N. A.
Davis, T. L.
Giladi, N.
Gurevich, T.
Hauser, R. A.
Jankovic, J.
Lyons, K. E.
Marsh, L.
Miyasaki, J. M.
Morgan, J. C.
Santiago, A. J.
Tarsy, D.
Mari, Z.
Malaty, I. A.
Nelson, E. C.
CA Natl Parkinson Fdn Quality
TI Mobility, mood and site of care impact health related quality of life in
Parkinson's disease
SO PARKINSONISM & RELATED DISORDERS
LA English
DT Article
DE Parkinson's disease; Health related quality of life; Best practices;
Quality improvement
ID CONTROLLED-TRIAL; MORTALITY; QUESTIONNAIRE; DEPRESSION; DISABILITY;
SYMPTOMS; NONMOTOR; CRITERIA
AB Objective: Examine the correlates of Health Related Quality of Life (HRQL) in a large cohort of Parkinson's disease (PD) patients from National Parkinson Foundation (NPF) Centers of Excellence (COEs).
Background: Improving outcomes for PD will depend upon uncovering disease features impacting HRQL to identify targets for intervention and variables for risk-adjustment models. Differences in HRQL outcomes between COEs could uncover modifiable aspects of care delivery.
Methods: This cross-sectional study examined the relative contribution of demographic, social, clinical and treatment features potentially related to HRQL, as measured by the PDQ-39, in 4601 consecutive subjects from 18 COEs. Stepwise linear regression was utilized to identify correlates of HRQL.
Results: The variability in the PDQ-39 summary index score correlated with MY stage (R-2 = 22%), Timed up and Go (TUG) (17%), disease duration (11%), comorbidities (8%), cognitive status (8%), antidepressant use (6%) and center at which a patient received care (5%). Stepwise regression reordered the importance of the variables, with the H&Y first and TUG and the center becoming equal and the second most important variables determining the PDQ-39 total score. All independent variables together accounted for 44% of the variability in HRQL.
Conclusions: We confirmed many but not all HRQL associations found in smaller studies. A novel observation was that the site of care was an important contributor to HRQL, suggesting that comparison of outcomes and processes among centers may identify best practices. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Nutt, J. G.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA.
[Siderowf, A. D.; Dahodwala, N. A.] Univ Penn, Philadelphia, PA 19104 USA.
[Guttman, M.] Univ Toronto, Toronto, ON M5S 1A1, Canada.
[Schmidt, P. N.; Zamudio, J. I.; Okun, M. S.] Natl Parkinson Fdn, Miami, FL USA.
[Wu, S. S.; Malaty, I. A.] Univ Florida, Gainesville, FL 32611 USA.
[Simuni, T.] Northwestern Univ, Evanston, IL 60208 USA.
[Parashos, F. S. A.] Struthers Parkinson Ctr, Golden Valley, MN USA.
[Davis, T. L.] Vanderbilt Univ, Nashville, TN USA.
[Giladi, N.; Gurevich, T.] Tel Aviv Sourasky Med Ctr, Tel Aviv, Israel.
[Hauser, R. A.] Univ S Florida, Tampa, FL 33620 USA.
[Jankovic, J.] Baylor Coll Med, Houston, TX 77030 USA.
[Lyons, K. E.] Univ Kansas, Lawrence, KS 66045 USA.
[Marsh, L.] DeBakey Vet Affairs Med Ctr, Houston, TX USA.
[Morgan, J. C.] Georgia Regents Univ, Augusta, GA USA.
[Santiago, A. J.] Muhammad Ali Parkinson Ctr, Phoenix, AZ USA.
[Santiago, A. J.] Barrow Neurol Inst, Phoenix, AZ USA.
[Tarsy, D.] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA.
[Mari, Z.] Johns Hopkins Med Ctr, Baltimore, MD USA.
[Nelson, E. C.] Dartmouth Hitchcock Med Ctr, Lebanon, NH USA.
RP Nutt, JG (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA.
EM nuttj@ohsu.edu
OI Okun, Michael/0000-0002-6247-9358; Miyasaki, Janis/0000-0002-6372-6007
FU National Parkinson Foundation
FX National Parkinson Foundation.
NR 29
TC 5
Z9 5
U1 3
U2 9
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 MAR
PY 2014
VL 20
IS 3
BP 274
EP 279
DI 10.1016/j.parkreldis.2013.10.004
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA AK4RX
UT WOS:000338412900002
PM 24182524
ER
PT J
AU Bellows, CF
Robinson, C
Fitzgibbons, RJ
Webber, LS
Berger, DH
AF Bellows, Charles F.
Robinson, Celia
Fitzgibbons, Robert J., Jr.
Webber, Larry S.
Berger, David H.
TI Watchful Waiting for Ventral Hernias: A Longitudinal Study
SO AMERICAN SURGEON
LA English
DT Article
ID QUALITY-OF-LIFE; INCISIONAL HERNIA; INGUINAL-HERNIA; CLINICAL-TRIAL;
REPAIR
AB Ventral hernias are a common clinical problem. Immediate repair is recommended for most ventral hernias despite significant recurrence rates. This practice may be related to a lack of understanding of the natural history of ventral hernias. The purpose of this study was to determine the natural history of ventral hernias and to determine if watchful waiting is an acceptable and safe option. Forty-one patients with ventral hernias were enrolled in a longitudinal cohort study of watchful waiting. Primary outcomes were functional impairment resulting from hernia disease as measured by the Activities Assessment Scale (AAS) and changes from baseline to two years in the physical and mental component score of the SF-36 Health Survey. Secondary outcomes included complications such as incarceration. Mixed-effects model for repeated measures and Student's t tests were used to evaluate scale performance. The mean age of enrollees was 64 years, and the mean hernia size was 239 cm(2). Eleven patients were lost to follow-up, and seven patients died of other causes. All remaining patients were followed for two years. There was one incarceration during the follow-up period. There was no deterioration in the AAS score (baseline vs 24 months = 28 vs 25, P = 0.60). There was deterioration of the physical functioning dimension of the SF-36 (baseline vs 24 months = 40 vs 32, P < 0.01), but the mental functioning dimension was improved (45 vs 51; P = 0.01). Watchful waiting was a safe option for patients in this study with ventral hernias.
C1 [Bellows, Charles F.; Fitzgibbons, Robert J., Jr.] Tulane Univ, Dept Surg, New Orleans, LA 70115 USA.
[Robinson, Celia; Berger, David H.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Houston, TX 77030 USA.
[Webber, Larry S.] Creighton Univ, Sch Med, Omaha, NE USA.
RP Bellows, CF (reprint author), Tulane Univ, Dept Surg, 1430 Tulane Ave, New Orleans, LA 70115 USA.
EM cbellows@tulane.edu
NR 18
TC 11
Z9 11
U1 0
U2 1
PU SOUTHEASTERN SURGICAL CONGRESS
PI CUMMING
PA 115 SAMARITAN DR, #200, CUMMING, GA 30040-2354 USA
SN 0003-1348
EI 1555-9823
J9 AM SURGEON
JI Am. Surg.
PD MAR
PY 2014
VL 80
IS 3
BP 245
EP 252
PG 8
WC Surgery
SC Surgery
GA AJ5RJ
UT WOS:000337743400019
PM 24666865
ER
PT J
AU Berry, C
Ley, EJ
Margulies, DR
Pruett, J
Miller, C
Bukur, M
Palestrant, D
Malinoski, D
Salim, A
AF Berry, Cherisse
Ley, Eric J.
Margulies, Daniel R.
Pruett, Jessica
Miller, Chad
Bukur, Marko
Palestrant, David
Malinoski, Darren
Salim, Ali
TI Prospective Evaluation of Posttraumatic Vasospasm: Determining Its
Clinical Significance after Traumatic Brain Injury
SO AMERICAN SURGEON
LA English
DT Article
C1 [Berry, Cherisse; Ley, Eric J.; Margulies, Daniel R.; Pruett, Jessica] Cedars Sinai Med Ctr, Dept Surg, Div Trauma & Crit Care, Los Angeles, CA 90048 USA.
[Miller, Chad] Wexner Med Ctr, Dept Neurol, Div Cerebrovasc Dis & Neurocrit Care, Columbus, OH USA.
[Bukur, Marko] Broward Hlth & Del Ray Med Ctr, Dept Trauma & Crit Care, Ft Lauderdale, FL USA.
[Palestrant, David] Cedars Sinai Med Ctr, Dept Neurol, Div Neurocrit Care, Los Angeles, CA 90048 USA.
[Malinoski, Darren] Portland VA Med Ctr, Surg Crit Care Sect, Portland, OR USA.
[Salim, Ali] Brigham & Womens Hosp, Dept Surg, Div Trauma Burns & Surg Crit Care, Boston, MA 02115 USA.
RP Salim, A (reprint author), Brigham & Womens Hosp, Dept Surg, Div Trauma Burns & Surg Crit Care, 75 Francis St, Boston, MA 02115 USA.
EM asalim1@partners.org
NR 4
TC 1
Z9 1
U1 0
U2 0
PU SOUTHEASTERN SURGICAL CONGRESS
PI CUMMING
PA 115 SAMARITAN DR, #200, CUMMING, GA 30040-2354 USA
SN 0003-1348
EI 1555-9823
J9 AM SURGEON
JI Am. Surg.
PD MAR
PY 2014
VL 80
IS 3
BP 310
EP 312
PG 3
WC Surgery
SC Surgery
GA AJ5RJ
UT WOS:000337743400030
PM 24666876
ER
PT J
AU Paulson, D
Bowen, ME
Lichtenberg, PA
AF Paulson, Daniel
Bowen, Mary Elizabeth
Lichtenberg, Peter A.
TI Does Brain Reserve Protect Older Women from Vascular Depression?
SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL
SCIENCES
LA English
DT Article
DE Cerebrovascular burden; Education; Mood
ID LATE-LIFE DEPRESSION; COGNITIVE RESERVE; RISK-FACTORS; GERIATRIC
DEPRESSION; SYMPTOMS; STROKE; ADULTS; HYPOTHESIS; MORTALITY; SAMPLE
AB Objectives. Brain reserve theory, typically discussed in relation to dementia, was examined with regard to late-life depression symptomatology and cerebrovascular burden (CVB) in older-old women.
Method. It was predicted that in a 6-year longitudinal sample (Health and Retirement Study) of 1,355 stroke-free women aged 80 years and older, higher levels of depressive symptomatology (8-item Center for Epidemiologic Studies-Depression score) would be predicted by high CVB, less educational attainment, and the education x CVB interaction after controlling for age and cognitive functioning (Telephone Interview for Cognitive Status). A latent growth curve model was used to identify differences in depression symptomatology at baseline and over time. Logistic regression analyses were used to predict clinically significant depressive symptomatology at each wave based on CVB, education, and the education x CVB interaction.
Results. Results indicate that among older women, greater educational attainment predicted fewer depression symptoms at baseline, but this advantage was partially eroded over time. The education x CVB interaction predicted clinically significant depressive symptoms at baseline when the benefits of education were most robust.
Discussion. Brain reserve, characterized by educational attainment, may counterbalance the effect of high CVB with respect to depressive symptoms, thereby preserving mood in late life. These findings support the application of brain reserve theory to late-life depression.
C1 [Paulson, Daniel; Lichtenberg, Peter A.] Wayne State Univ, Inst Gerontol, Detroit, MI 48202 USA.
[Paulson, Daniel; Lichtenberg, Peter A.] Wayne State Univ, Dept Psychol, Detroit, MI 48202 USA.
[Paulson, Daniel] Ralph H Johnson VA Med Ctr, Dept Mental Hlth, Charleston, SC USA.
[Bowen, Mary Elizabeth] Vet Hlth Adm, HSR & D RR & D Ctr Excellence, Tampa, FL USA.
RP Paulson, D (reprint author), Wayne State Univ, Inst Gerontol, 87 East Ferry St,226 Knapp Bldg, Detroit, MI 48202 USA.
EM Paulson@wayne.edu
FU Blue Cross Blue Shield of Michigan Foundation [1680.SAP]; T32 grant
[T-32 AG00275-06]
FX This work was generously supported by the Blue Cross Blue Shield of
Michigan Foundation (1680.SAP); and by the T32 grant-supported NIH
Pre-Doctoral Training Program in Aging and Urban Health at the Institute
of Gerontology (T-32 AG00275-06).
NR 55
TC 4
Z9 4
U1 0
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5014
EI 1758-5368
J9 J GERONTOL B-PSYCHOL
JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci.
PD MAR
PY 2014
VL 69
IS 2
BP 157
EP 167
DI 10.1093/geronb/gbt007
PG 11
WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology,
Multidisciplinary
SC Geriatrics & Gerontology; Psychology
GA AJ9EG
UT WOS:000338009400002
PM 23448867
ER
PT J
AU Hilton, J
Arnaout, A
Clemons, M
AF Hilton, John
Arnaout, Angel
Clemons, Mark
TI Primary endocrine therapy as an approach for patients with localized
breast cancer deemed not to be surgical candidates
SO CURRENT OPINION IN SUPPORTIVE AND PALLIATIVE CARE
LA English
DT Review
DE elderly; estrogen-receptor-positive breast cancer; nonsurgical
candidates; primary endocrine therapy
ID ESTROGEN-RECEPTOR-ALPHA; KINASE 4/6 INHIBITOR; ANTIESTROGEN RESISTANCE;
PD 0332991; NEOADJUVANT LETROZOLE; POSTMENOPAUSAL WOMEN; AROMATASE
INHIBITOR; ADJUVANT TAMOXIFEN; RANDOMIZED-TRIAL; ELDERLY-WOMEN
AB Purpose of review
For women diagnosed with localized hormone-receptor-positive breast cancer who have a poor performance status or who have medical conditions precluding aggressive treatment with chemotherapy or surgery, primary endocrine therapy has been proposed as a therapeutic alternative. Given that society is rapidly aging overall, this subset of patients will likely become a greater proportion of the patient population seen by breast cancer specialists.
Recent findings
On the basis of the results from randomized trials in patients whose health does not permit surgery, it appears that tamoxifen achieves a similar overall survival compared with surgery plus tamoxifen, supporting the use of primary endocrine therapy. In the neoadjuvant setting, aromatase inhibitors appear superior to tamoxifen, suggesting that these agents may be the best choice in the primary endocrine therapy setting. In addition, new breakthroughs for the management of hormone-receptor-positive disease in the metastatic setting have recently been reported.
Summary
This review will discuss the rationale and evidence for primary endocrine therapy; which agents could be selected for use; and how recent advances for the management of hormone-receptor-positive disease may potentially apply to this population.
C1 [Hilton, John] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Arnaout, Angel] Ottawa Gen Hosp, Dept Surg, Ottawa, ON K1H 8L6, Canada.
[Arnaout, Angel; Clemons, Mark] Ottawa Hosp Res Inst, Ottawa, ON, Canada.
[Clemons, Mark] Ottawa Gen Hosp, Dept Med, Div Med Oncol, Ottawa, ON K1H 8L6, Canada.
RP Hilton, J (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Early Drug Dev Ctr, 450 Brookline Ave, Boston, MA 02215 USA.
EM john_hilton@dfci.harvard.edu
NR 38
TC 3
Z9 3
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1751-4258
EI 1751-4266
J9 CURR OPIN SUPPORT PA
JI Curr. Opin Support Palliat. Car.
PD MAR
PY 2014
VL 8
IS 1
BP 53
EP 58
DI 10.1097/SPC.0000000000000026
PG 6
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA AJ2MI
UT WOS:000337489700010
PM 24299966
ER
PT J
AU Gorrindo, T
Chevalier, L
Goldfarb, E
Hoeppner, BB
Birnbaum, RJ
AF Gorrindo, Tristan
Chevalier, Lydia
Goldfarb, Elizabeth
Hoeppner, Bettina B.
Birnbaum, Robert J.
TI Autonomic Arousal and Learning in Web-Based Simulation: A Feasibility
Study
SO JOURNAL OF CONTINUING EDUCATION IN THE HEALTH PROFESSIONS
LA English
DT Article
DE online; computer-based education; program planning; curriculum
development; simulation; self-directed learning; continuing medical
education; engagement; online learning; pedagogy; physiology
ID SKIN-CONDUCTANCE RESPONSES
AB Introduction Autonomic arousal is an important component of understanding learning as it is related to cognitive effort, attention, and emotional arousal. Currently, however, little is known about its relationship to online education. We conducted a study to determine the feasibility of measuring autonomic arousal and engagement in online continuing medical education (CME). Method Using the Computer Simulation Assessment Tool (CSAT) platform, health care providers were randomly assigned to either high- or low-valence versions of a Web-based simulation on risk assessment for a returning veteran. Data were collected on participants' actions within the simulation, self-reported cognitive engagement, knowledge retention, and autonomic arousal measured using galvanic skin response (GSR). Results Participants in the high-valence condition (n = 7) chose a lower percentage of critical actions (M = 79.2, SD = 4.2) than participants in the low valence (n = 8) condition (M = 83.9, SD = 3.6, t(1,14) = 2.44, p = .03). While not statistically significant, high-valence participants reported higher cognitive engagement. Participants in the high-valence condition showed a larger increase in physiologic arousal when comparing mean tonic GSR during the orientation simulation to the study simulation (high-valence mean difference = 4.21 S, SD = 1.23 vs low-valence mean difference = 1.64 S, SD = 2.32, t(1,13) = -2.62, p = .01). Discussion In addition to being consistent with previous engagement research, this experiment functioned as a feasibility study for measuring autonomic arousal in online CME. The current study provides a framework for future studies, which may use neurophysiology to identify the critical autonomic and engagement components associated with effective online learning.
C1 [Gorrindo, Tristan; Birnbaum, Robert J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA.
[Chevalier, Lydia; Goldfarb, Elizabeth] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hoeppner, Bettina B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Addict Med, Cambridge, MA 02138 USA.
RP Gorrindo, T (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,Ste 700, Boston, MA 02114 USA.
EM tristan.gorrindo@mgh.harvard.edu
NR 17
TC 2
Z9 2
U1 1
U2 3
PU WILEY PERIODICALS, INC
PI SAN FRANCISCO
PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA
SN 0894-1912
EI 1554-558X
J9 J CONTIN EDUC HEALTH
JI J. Contin. Educ. Health Prof.
PD SPR
PY 2014
VL 34
SU 1
BP S17
EP S22
DI 10.1002/chp.21234
PG 6
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA AJ4FZ
UT WOS:000337629500005
PM 24935879
ER
PT J
AU Hertzman-Miller, R
Beverly, E
Goodrich, A
AF Hertzman-Miller, Ruth
Beverly, Elizabeth
Goodrich, Anne
TI An Assessment of Primary Care Providers' Educational Needs Regarding
Treatment for Type 2 Diabetes Mellitus
SO JOURNAL OF CONTINUING EDUCATION IN THE HEALTH PROFESSIONS
LA English
DT Article
DE gap analysis; needs assessment; mixed methods research;
profession-physicians
C1 [Hertzman-Miller, Ruth] Med Programs, Athens, OH USA.
[Beverly, Elizabeth] Ohio Univ, Inst Diabet, Athens, OH 45701 USA.
[Goodrich, Anne] Humedica Inc, Strateg Alliances, Boston, MA USA.
RP Hertzman-Miller, R (reprint author), Joslin Diabet Ctr Profess Educ, 1 Joslin Pl,Rm 719, Boston, MA 02215 USA.
EM ruth.hertzman-miller@joslin.harvard.edu
FU Sanofi-Aventis
FX The authors report funding support was given by Sanofi-Aventis for the
conduct of the presently reported study.
NR 4
TC 1
Z9 1
U1 0
U2 0
PU WILEY PERIODICALS, INC
PI SAN FRANCISCO
PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA
SN 0894-1912
EI 1554-558X
J9 J CONTIN EDUC HEALTH
JI J. Contin. Educ. Health Prof.
PD SPR
PY 2014
VL 34
SU 1
BP S32
EP S33
DI 10.1002/chp.21223
PG 2
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA AJ4FZ
UT WOS:000337629500008
ER
PT J
AU Guddati, AK
Joy, PS
Marak, CP
AF Guddati, Achuta K.
Joy, Parijat S.
Marak, Creticus P.
TI Dose adjustment of carboplatin in patients on hemodialysis
SO MEDICAL ONCOLOGY
LA English
DT Article
DE Carboplatin; AUC; Dose; Hemodialysis
ID CELL LUNG-CANCER; DEPENDENT RENAL-INSUFFICIENCY; ADVANCED
OVARIAN-CANCER; COMBINATION CHEMOTHERAPY; PHARMACOKINETIC ANALYSIS;
FORMULA; DOSAGE; PACLITAXEL; CISPLATIN; ETOPOSIDE
AB Carboplatin is one of the most prescribed cytotoxic drug, which is extensively used in the treatment regimens of several malignancies. The therapeutic efficiency of carboplatin has been found to correlate the area under curve (AUC). The Calvert formula has been extensively used to determine the dose of carboplatin for a fixed AUC and glomerular filtration rate (GFR). This formula has also been used in patients with end-stage renal disease on hemodialysis by assuming that the GFR is zero. This is applicable to patients who receive hemodialysis within 12-18 h after carboplatin infusion. After the first 24 h, a majority of the carboplatin is bound to proteins is not easily dialyzable and hence continues to remain in the blood stream despite repeated sessions of hemodialysis. We derive a correction factor to calculate the resultant AUC in such patients. The analysis done by using this correction factor shows that the AUC can increase by eightfold in patients who received the adjusted dose but whose hemodialysis was delayed beyond 24 h after infusion. The correction factor proposed here can also be used to calculate the dose adjustment required a priori in patients who may receive delayed hemodialysis. It is also useful to predict the AUC and estimate the resultant toxicity in such patients.
C1 [Guddati, Achuta K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med, Boston, MA 02163 USA.
[Joy, Parijat S.] Univ Iowa, Univ Iowa Hosp & Clin, Dept Internal Med, Iowa City, IA 52242 USA.
[Marak, Creticus P.] Tahlequah City Hosp, Dept Med, Div Pulm Med, Tahlequah, OK 74464 USA.
RP Guddati, AK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med, 50 Fruit St, Boston, MA 02163 USA.
EM aguddati@partners.org
NR 28
TC 2
Z9 2
U1 0
U2 3
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1357-0560
EI 1559-131X
J9 MED ONCOL
JI Med. Oncol.
PD MAR
PY 2014
VL 31
IS 3
AR 848
DI 10.1007/s12032-014-0848-0
PG 5
WC Oncology
SC Oncology
GA AJ5MV
UT WOS:000337728700014
PM 24452283
ER
PT J
AU Di Paolo, NC
Baldwin, LK
Irons, EE
Papayannopoulou, T
Tomlinson, S
Shayakhmetov, DM
AF Di Paolo, Nelson C.
Baldwin, Lisa K.
Irons, Eric E.
Papayannopoulou, Thalia
Tomlinson, Stephen
Shayakhmetov, Dmitry M.
TI IL-1 alpha and Complement Cooperate in Triggering Local Neutrophilic
Inflammation in Response to Adenovirus and Eliminating Virus-Containing
Cells
SO PLOS PATHOGENS
LA English
DT Article
ID INNATE IMMUNE-RESPONSE; IN-VIVO; GENE-TRANSFER; IMMUNOCOMPROMISED
PATIENTS; INTRAVENOUS-INJECTION; STERILE INFLAMMATION; ALTERNATIVE
PATHWAY; CXCR4 ANTAGONIST; MICE DEFICIENT; KUPFFER CELLS
AB Inflammation is a highly coordinated host response to infection, injury, or cell stress. In most instances, the inflammatory response is pro-survival and is aimed at restoring physiological tissue homeostasis and eliminating invading pathogens, although exuberant inflammation can lead to tissue damage and death. Intravascular injection of adenovirus (Ad) results in virus accumulation in resident tissue macrophages that trigger activation of CXCL1 and CXCL2 chemokines via the IL-1 alpha-IL-1RI signaling pathway. However, the mechanistic role and functional significance of this pathway in orchestrating cellular inflammatory responses to the virus in vivo remain unclear. Resident metallophilic macrophages expressing macrophage receptor with collagenous structure (MARCO(+)) in the splenic marginal zone (MZ) play the principal role in trapping Ad from the blood. Here we show that intravascular Ad administration leads to the rapid recruitment of Ly-6G(+)7/4(+) polymorphonuclear leukocytes (PMNs) in the splenic MZ, the anatomical compartment that remains free of PMNs when these cells are purged from the bone marrow via a non-inflammatory stimulus. Furthermore, PMN recruitment in the splenic MZ resulted in elimination of virus-containing cells. IL-1a-IL-1RI signaling is only partially responsible for PMN recruitment in the MZ and requires CXCR2, but not CXCR1 signaling. We further found reduced recruitment of PMNs in the splenic MZ in complement C3-deficient mice, and that pre-treatment of IL-1 alpha-deficient, but not wild-type mice, with complement inhibitor CR2-Crry (inhibits all complement pathways at C3 activation) or CR2-fH (inhibits only the alternative complement activation pathway) prior to Ad infection, abrogates PMN recruitment to the MZ and prevents elimination of MARCO(+) macrophages from the spleen. Collectively, our study reveals a non-redundant role of the molecular factors of innate immunity - the chemokine-activating IL-1 alpha-IL-1RI-CXCR2 axis and complement - in orchestrating local inflammation and functional cooperation of PMNs and resident macrophages in the splenic MZ, which collectively contribute to limiting disseminated pathogen spread via elimination of virus-containing cells.
C1 [Di Paolo, Nelson C.; Shayakhmetov, Dmitry M.] Emory Univ, Sch Med, Dept Pediat, Lowance Ctr Human Immunol, Atlanta, GA 30322 USA.
[Di Paolo, Nelson C.; Shayakhmetov, Dmitry M.] Emory Univ, Sch Med, Dept Med, Lowance Ctr Human Immunol, Atlanta, GA USA.
[Baldwin, Lisa K.; Irons, Eric E.] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA.
[Papayannopoulou, Thalia] Univ Washington, Dept Med, Div Hematol, Seattle, WA 98195 USA.
[Tomlinson, Stephen] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA.
[Tomlinson, Stephen] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
RP Di Paolo, NC (reprint author), Emory Univ, Sch Med, Dept Pediat, Lowance Ctr Human Immunol, Atlanta, GA 30322 USA.
EM dmitryshay@emory.edu
FU US NIH [AI065429, CA141439, CA158179]; VA [BX001218]
FX This study was supported by US NIH grants AI065429 and CA141439 to DMS,
CA158179 to ST, and VA grant BX001218 to ST. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 74
TC 7
Z9 7
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAR
PY 2014
VL 10
IS 3
AR e1004035
DI 10.1371/journal.ppat.1004035
PG 19
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AJ2FF
UT WOS:000337470300065
PM 24651866
ER
PT J
AU Zhang, YJ
Lenart, BA
Lee, JK
Chen, D
Shi, P
Ren, J
Muehleman, C
Chen, D
An, HS
AF Zhang, Yejia
Lenart, Brett A.
Lee, Joseph K.
Chen, Ding
Shi, Peng
Ren, Jing
Muehleman, Carol
Chen, Di
An, Howard S.
TI Histological Features of Endplates of the Mammalian Spine From Mice to
Men
SO SPINE
LA English
DT Article
DE endplate; intervertebral disc; mammals; human
ID INTERVERTEBRAL DISC DEGENERATION; HUMAN LUMBAR DISC; SOLUTE TRANSPORT;
ANIMAL-MODELS; NUTRITION; COMPRESSION; VERTEBRAE; DENSITY; WINNER
AB Study Design. Histological features of the intervertebral disc (IVD)-endplate interface were analyzed.
Objective. To define cartilaginous and bony vertebral endplate in commonly used laboratory animals and compare with that of the humans.
Summary of Background Data. Endplates are crucial for the IVD nutrient supply: the IVDs have limited blood supply; most nutrients diffuse through endplates to nourish the discs. Various animal models of IVD and endplate degeneration have been used to study the etiology and treatments of spinal disorders. However, because humans are biped, the spine mechanics differ significantly from other mammals. Translation of animal research findings requires a characterization and comparison of the vertebral endplate in the respective species. In this study, we compared the endplate structure of laboratory animal species at the age range commonly used for modeling spine degeneration with that of an adult human.
Methods. Mouse, rat, rabbit, goat, and human IVDs and the adjacent vertebral bodies were isolated from the lower lumbar spine. Tissues were stained with Alcian Blue, counterstained with hematoxylin and eosin.
Results. Structure of the vertebral endplate varied significantly between the adult animal species and that of the humans. Growth plates persisted in all adult animals studied, whereas the growth plate is absent in the adult humans. In the mice and rats, the cartilaginous endplates are in continuation with the growth plates, with only a small bony center. Rabbits and goats have a bony layer between cartilaginous endplate and the growth plate. The human endplate consist of a cartilaginous layer and the bony endplate.
Conclusion. Significant differences exist in histological features of the endplate across animal species and that of the humans. Consideration should be given when animal models are used to study IVD degeneration and surgical treatments.
C1 [Zhang, Yejia; Lenart, Brett A.; Lee, Joseph K.; Chen, Ding; Shi, Peng; An, Howard S.] Rush Univ, Med Ctr, Dept Orthoped Surg, Chicago, IL 60612 USA.
[Zhang, Yejia] Rush Univ, Med Ctr, Dept Phys Med & Rehabil, Chicago, IL 60612 USA.
[Zhang, Yejia; Muehleman, Carol; Chen, Di] Rush Univ, Med Ctr, Dept Biochem, Chicago, IL 60612 USA.
[Zhang, Yejia] Univ Penn, Perelman Sch Med, Dept Phys Med & Rehabil, Philadelphia, PA 19104 USA.
[Zhang, Yejia] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Chen, Ding] Cent S Univ, Hosp Xiangya 2, Dept Orthoped Surg, Changsha, Hunan, Peoples R China.
[Ren, Jing] Qujing 1 Hosp, Dept Orthoped, Qujing, Yunnan Province, Peoples R China.
RP Zhang, YJ (reprint author), Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
EM yejia.zhang@uphs.upenn.edu
FU NIAMS NIH HHS [R01 AR054465, R01 AR055915]; NICHD NIH HHS [K08 HD049598]
NR 25
TC 9
Z9 11
U1 4
U2 14
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0362-2436
EI 1528-1159
J9 SPINE
JI SPINE
PD MAR 1
PY 2014
VL 39
IS 5
BP E312
EP E317
DI 10.1097/BRS.0000000000000174
PG 6
WC Clinical Neurology; Orthopedics
SC Neurosciences & Neurology; Orthopedics
GA AJ1BN
UT WOS:000337390700003
PM 24365894
ER
PT J
AU Mhatre, SD
Satyasi, V
Killen, M
Paddock, BE
Moir, RD
Saunders, AJ
Marenda, DR
AF Mhatre, Siddhita D.
Satyasi, Vivek
Killen, Mark
Paddock, Brie E.
Moir, Robert D.
Saunders, Aleister J.
Marenda, Daniel R.
TI Synaptic abnormalities in a Drosophila model of Alzheimer's disease
SO DISEASE MODELS & MECHANISMS
LA English
DT Article
DE APP; Alzheimer's disease; Drosophila; BACE; Synapse; NMJ
ID AMYLOID PRECURSOR PROTEIN; LARVAL NEUROMUSCULAR-JUNCTION;
CYSTEINE-STRING PROTEIN; A-BETA OLIGOMERS; MOUSE MODEL; OXIDATIVE
DAMAGE; DISCS-LARGE; NEURODEGENERATIVE DISEASES; MITOCHONDRIAL
DYSFUNCTION; AXONAL-TRANSPORT
AB Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by memory loss and decreased synaptic function. Advances in transgenic animal models of AD have facilitated our understanding of this disorder, and have aided in the development, speed and efficiency of testing potential therapeutics. Recently, we have described the characterization of a novel model of AD in the fruit fly, Drosophila melanogaster, where we expressed the human AD-associated proteins APP and BACE in the central nervous system of the fly. Here we describe synaptic defects in the larval neuromuscular junction (NMJ) in this model. Our results indicate that expression of human APP and BACE at the larval NMJ leads to defective larval locomotion behavior, decreased presynaptic connections, altered mitochondrial localization in presynaptic motor neurons and decreased postsynaptic protein levels. Treating larvae expressing APP and BACE with the.-secretase inhibitor L-685,458 suppresses the behavioral defects as well as the pre- and postsynaptic defects. We suggest that this model will be useful to assess and model the synaptic dysfunction normally associated with AD, and will also serve as a powerful in vivo tool for rapid testing of potential therapeutics for AD.
C1 [Mhatre, Siddhita D.; Satyasi, Vivek; Killen, Mark; Saunders, Aleister J.; Marenda, Daniel R.] Drexel Univ, Dept Biol, Philadelphia, PA 19104 USA.
[Paddock, Brie E.] Arcadia Univ, Dept Biol, Glenside, PA 19038 USA.
[Moir, Robert D.] Harvard Univ, Massachusetts Gen Hosp, Genet & Aging Res Unit, MIND,Sch Med, Boston, MA 02114 USA.
[Saunders, Aleister J.] Drexel Univ, Dept Biochem & Mol Biol, Coll Med, Philadelphia, PA 19104 USA.
[Saunders, Aleister J.; Marenda, Daniel R.] Drexel Univ, Dept Neurobiol & Anat, Coll Med, Philadelphia, PA 19104 USA.
RP Marenda, DR (reprint author), Drexel Univ, Dept Biol, Philadelphia, PA 19104 USA.
EM daniel.marenda@drexel.edu
FU National Institutes of Health [R01NS057295, R21 RR026074]; National
Science Foundation [IOS 1256114]
FX Work in the Saunders lab is supported by the National Institutes of
Health, grant R01NS057295 to A.J.S.; work in the Marenda lab is
supported by the National Institutes of Health, grant R21 RR026074 to
D.R.M., and from the National Science Foundation IOS 1256114 to D.R.M.
NR 75
TC 10
Z9 11
U1 2
U2 21
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 1754-8403
EI 1754-8411
J9 DIS MODEL MECH
JI Dis. Model. Mech.
PD MAR
PY 2014
VL 7
IS 3
BP 373
EP 385
DI 10.1242/dmm.012104
PG 13
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA AJ4DF
UT WOS:000337620300008
PM 24487408
ER
PT J
AU Cadoni, S
Gallittu, P
Sanna, S
Fanari, V
Porcedda, ML
Erriu, M
Leung, FW
AF Cadoni, Sergio
Gallittu, Paolo
Sanna, Stefano
Fanari, Viviana
Porcedda, Maria L.
Erriu, Matteo
Leung, Felix W.
TI A two-center randomized controlled trial of water-aided colonoscopy
versus air insufflation colonoscopy
SO ENDOSCOPY
LA English
DT Article
ID UNSEDATED COLONOSCOPY; WARM WATER; CECAL INTUBATION; QUALITY INDICATORS;
COLORECTAL-CANCER; US VETERANS; SEDATION; INFUSION; IMMERSION; EXCHANGE
AB Background and study aim: Water-aided colonoscopy includes water immersion and water exchange. Several small single-center studies have suggested that the use of water rather than air insufflation during colonoscopy reduces pain on insertion. The aim of this study was to investigate whether water-aided colonoscopy is less painful than air insufflation in a large cohort of patients.
Patients and methods: This was a two-center, randomized controlled trial. Consecutive patients who agreed to start colonoscopy without premedication were included. Sedation was administered on demand. Water-aided colonoscopy was performed using water immersion in the early phase of the study, and subsequently water exchange was used. The primary endpoint was cecal intubation with pain scores of <= 2 and sedation with no or <= 2mg midazolam. Secondary outcomes were pain score at discharge, cecal intubation rate and time, and adenoma detection rate (ADR).
Results: A total of 672 patients were randomized to water exchange (n=338) or air insufflation (n=334). The primary endpoint was achieved in more patients in the water exchange group (83.8% vs. 62%; P<0.0005). On-demand sedation was also required less (11.5% vs. 26.0 %; P<0.0005) and mean pain score was lower (1.3 vs. 2.3; P<0.0005) in the water exchange group. The cecal intubation rates were comparable. Water exchange had a significantly higher overall ADR (25.8% vs. 19.1 %; P=0.041), proximal ADR (10.1% vs. 4.8 %; P=0.014), and proximal <10mm ADR (7.7% vs. 3.9 %; P=0.046); proximal ADR was also higher in screening-only patients in the water exchange group (18.9% vs. 7.4 %; P=0.015). No detailed analysis was possible for the air insufflation vs. water immersion comparison.
Conclusion: The current results confirmed that water exchange minimized the requirement for sedation and increased the ADR.
C1 [Cadoni, Sergio; Gallittu, Paolo] S Barbara Hosp, Digest Endoscopy Unit, Iglesias, Carbonia Iglesi, Italy.
[Sanna, Stefano; Fanari, Viviana; Porcedda, Maria L.] NS di Bonaria Hosp, Digest Endoscopy Unit, San Gavino Monreale, Villacidro Sanl, Italy.
[Erriu, Matteo] Univ Cagliari, Dept Surg, Cagliari, Italy.
[Leung, Felix W.] Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, North Hills, CA USA.
[Leung, Felix W.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
RP Cadoni, S (reprint author), S Barbara Hosp, Digest Endoscopy Unit, Via S Leonardo 1, I-09016 Iglesias, CI, Italy.
EM cadonisergio@gmail.com
OI Erriu, Matteo/0000-0002-9818-5861
NR 34
TC 18
Z9 18
U1 0
U2 5
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0013-726X
EI 1438-8812
J9 ENDOSCOPY
JI Endoscopy
PD MAR
PY 2014
VL 46
IS 3
BP 212
EP 218
DI 10.1055/s-0033-1353604
PG 7
WC Gastroenterology & Hepatology; Surgery
SC Gastroenterology & Hepatology; Surgery
GA AI8HL
UT WOS:000337152400009
PM 24218307
ER
PT J
AU Edlow, BL
McNab, JA
Witzel, T
van der Kouwe, A
Stevens, A
Vinke, L
Ebling, M
Frosch, MP
Schwamm, LH
Greenberg, SM
Wu, O
Wald, LL
Perl, DP
Fischl, B
Kinney, HC
Folkerth, RD
AF Edlow, B. L.
McNab, J. A.
Witzel, T.
van der Kouwe, A.
Stevens, A.
Vinke, L.
Ebling, M.
Frosch, M. P.
Schwamm, L. H.
Greenberg, S. M.
Wu, O.
Wald, L. L.
Perl, D. P.
Fischl, B.
Kinney, H. C.
Folkerth, R. D.
TI Integration of Advanced Imaging and Histopathology to Determine the
Neuroanatomic Basis of Traumatic Coma and Recovery of Consciousness
SO NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
LA English
DT Meeting Abstract
CT 115th Meeting of the British-Neuropathological-Society,
Institute-of-Child-Health
CY MAR 05-07, 2014
CL London, ENGLAND
SP British Neuropathol Soc, Inst Child Hlth
C1 [Edlow, B. L.; Schwamm, L. H.; Greenberg, S. M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Edlow, B. L.; McNab, J. A.; Witzel, T.; van der Kouwe, A.; Stevens, A.; Vinke, L.; Ebling, M.; Wu, O.; Wald, L. L.; Fischl, B.] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[McNab, J. A.] Stanford Univ, Dept Radiol, Palo Alto, CA 94305 USA.
[Frosch, M. P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Perl, D. P.] Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA.
[Kinney, H. C.; Folkerth, R. D.] Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Folkerth, R. D.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
EM bedlow@partners.org
RI Witzel, Thomas/P-1402-2014; Wald, Lawrence/D-4151-2009
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 0305-1846
EI 1365-2990
J9 NEUROPATH APPL NEURO
JI Neuropathol. Appl. Neurobiol.
PD MAR
PY 2014
VL 40
SU 1
SI SI
BP 27
EP 27
PG 1
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA AI9VX
UT WOS:000337291600031
ER
PT J
AU Bashirova, AA
Martin-Gayo, E
Jones, DC
Qi, Y
Apps, R
Gao, XJ
Burke, PS
Taylor, CJ
Rogich, J
Wolinsky, S
Bream, JH
Duggal, P
Hussain, S
Martinson, J
Weintrob, A
Kirk, GD
Fellay, J
Buchbinder, SP
Goedert, JJ
Deeks, SG
Pereyra, F
Trowsdale, J
Lichterfeld, M
Telenti, A
Walker, BD
Allen, RL
Carrington, M
Yu, XG
AF Bashirova, Arman A.
Martin-Gayo, Enrique
Jones, Des C.
Qi, Ying
Apps, Richard
Gao, Xiaojiang
Burke, Patrick S.
Taylor, Craig J.
Rogich, Jerome
Wolinsky, Steven
Bream, Jay H.
Duggal, Priya
Hussain, Shehnaz
Martinson, Jeremy
Weintrob, Amy
Kirk, Gregory D.
Fellay, Jacques
Buchbinder, Susan P.
Goedert, James J.
Deeks, Steven G.
Pereyra, Florencia
Trowsdale, John
Lichterfeld, Mathias
Telenti, Amalio
Walker, Bruce D.
Allen, Rachel L.
Carrington, Mary
Yu, Xu G.
TI LILRB2 Interaction with HLA Class I Correlates with Control of HIV-1
Infection
SO PLOS GENETICS
LA English
DT Article
ID MHC CLASS-I; INHIBITORY RECEPTOR; DENDRITIC CELLS; MYELOMONOCYTIC CELLS;
HOST CONTROL; MOLECULES; AIDS; COMPLEX; BINDING; ILT4
AB Natural progression of HIV-1 infection depends on genetic variation in the human major histocompatibility complex (MHC) class I locus, and the CD8(+) T cell response is thought to be a primary mechanism of this effect. However, polymorphism within the MHC may also alter innate immune activity against human immunodeficiency virus type 1 (HIV-1) by changing interactions of human leukocyte antigen (HLA) class I molecules with leukocyte immunoglobulin-like receptors (LILR), a group of immunoregulatory receptors mainly expressed on myelomonocytic cells including dendritic cells (DCs). We used previously characterized HLA allotype-specific binding capacities of LILRB1 and LILRB2 as well as data from a large cohort of HIV-1-infected individuals (N = 5126) to test whether LILR-HLA class I interactions influence viral load in HIV-1 infection. Our analyses in persons of European descent, the largest ethnic group examined, show that the effect of HLA-B alleles on HIV-1 control correlates with the binding strength between corresponding HLA-B allotypes and LILRB2 (p = 10(-2)). Moreover, overall binding strength of LILRB2 to classical HLA class I allotypes, defined by the HLA-A/B/C genotypes in each patient, positively associates with viral replication in the absence of therapy in patients of both European (p = 10(-11)-10(-9)) and African (p = 10(-5)-10(-3)) descent. This effect appears to be driven by variations in LILRB2 binding affinities to HLA-B and is independent of individual class I allelic effects that are not related to the LILRB2 function. Correspondingly, in vitro experiments suggest that strong LILRB2-HLA binding negatively affects antigen-presenting properties of DCs. Thus, we propose an impact of LILRB2 on HIV-1 disease outcomes through altered regulation of DCs by LILRB2-HLA engagement.
C1 [Bashirova, Arman A.; Qi, Ying; Apps, Richard; Gao, Xiaojiang; Carrington, Mary] Leidos Biomed Res Inc, Canc & Inflammat Program, Expt Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Bashirova, Arman A.; Martin-Gayo, Enrique; Burke, Patrick S.; Rogich, Jerome; Pereyra, Florencia; Walker, Bruce D.; Carrington, Mary; Yu, Xu G.] Ragon Inst MGH MIT & Harvard, Boston, MA USA.
[Jones, Des C.; Trowsdale, John] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England.
[Taylor, Craig J.] Addenbrookes Hosp, Tissue Typing Labs, Cambridge, England.
[Wolinsky, Steven] Northwestern Univ, Sch Med, Chicago, IL USA.
[Bream, Jay H.; Duggal, Priya] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA.
[Hussain, Shehnaz] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Los Angeles, CA USA.
[Martinson, Jeremy] Univ Pittsburgh, Pittsburgh, PA USA.
[Weintrob, Amy] USU Infect Dis Clin Res Program, Bethesda, MD USA.
[Kirk, Gregory D.] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA.
[Fellay, Jacques] Ecole Polytech Fed Lausanne, Sch Life Sci, Lausanne, Switzerland.
[Buchbinder, Susan P.] San Francisco Dept Publ Hlth, San Francisco, CA USA.
[Goedert, James J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Deeks, Steven G.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA.
[Pereyra, Florencia] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Lichterfeld, Mathias] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Telenti, Amalio] Univ Lausanne Hosp, Inst Microbiol, Lausanne, Switzerland.
[Telenti, Amalio] Univ Lausanne, Lausanne, Switzerland.
[Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Allen, Rachel L.] Univ London, St Georges Med Sch, London, England.
RP Bashirova, AA (reprint author), Leidos Biomed Res Inc, Canc & Inflammat Program, Expt Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
EM xyu@partners.org
RI SHCS, int. coll. A/G-4083-2011; Fellay, Jacques/A-6681-2009; SHCS,
all/G-4072-2011;
OI Fellay, Jacques/0000-0002-8240-939X; Martinson,
Jeremy/0000-0003-4673-7238; Wolinsky, Steven/0000-0002-9625-6697
FU Frederick National Laboratory for Cancer Research [HHSN261200800001E];
NIH, Frederick National Lab, Center for Cancer Research; NIAID [R01
AI087145, K24 AI069994, R24 AI067039]; UCSF/Gladstone CFAR [P30
AI027763]; UCSF CTSI [UL1 RR024131]; Center for AIDS Prevention Studies
[P30 MH62246]; Bill and Melinda Gates Foundation; AIDS Healthcare
Foundation; Harvard University Center for AIDS Research (CFAR), an NIH
[P30 AI060354]; NIAID, NIH; NCI, NIH; NICHD, NIH; NHLBI, NIH; NIDA, NIH;
NIMH, NIH; NIA, NIH; FIC, NIH; OAR, NIH; Swiss National Science
Foundation; NIH/NIAID [R01 AI078799, R56 AI098484, R01 AI087452, R01
AI089339]; MRC; Wellcome Trust; AICR; NIHR Cambridge BRC; National
Institute of Allergy and Infectious Diseases; National Cancer Institute;
National Heart, Lung, and Blood Institute [U01-AI-35042, UL1-RR025005,
U01-AI-35043, U01-AI-35039, U01-AI-35040, U01-AI-35041]
FX This project has been funded in whole or in part with federal funds from
the Frederick National Laboratory for Cancer Research, under Contract
No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
This Research was supported in part by the Intramural Research Program
of the NIH, Frederick National Lab, Center for Cancer Research. The
SCOPE cohort was supported in part by the NIAID (R01 AI087145, K24
AI069994, R24 AI067039), UCSF/Gladstone CFAR (P30 AI027763), the UCSF
CTSI (UL1 RR024131), and the Center for AIDS Prevention Studies (P30
MH62246). The International HIV Controllers Study (IHCS), was funded by
the Bill and Melinda Gates Foundation, the AIDS Healthcare Foundation
and the Harvard University Center for AIDS Research (CFAR), an NIH
funded program(P30 AI060354), which is supported by the following NIH
Co-Funding and Participating Institutes and Centers: NIAID, NCI, NICHD,
NHLBI, NIDA, NIMH, NIA, FIC and OAR. Members of the International HIV
Controllers Study can be found at www.hivcontrollers.org. The Swiss HIV
Cohort study (www.shcs.ch) is funded by the Swiss National Science
Foundation. XGY was supported by NIH/NIAID R01 AI078799, R56 AI098484,
R01 AI087452 and R01 AI089339. JT and DCJ were supported by the MRC,
Wellcome Trust and AICR, with partial funding from the NIHR Cambridge
BRC. We thank Randy Johnson and George Nelson for helpful discussions.
We are grateful to the USU Infectious Disease Clinical Research Program
HIV Working Group for collecting and providing clinical data. The MACS
clinical data used in this manuscript were collected at: The Johns
Hopkins Bloomberg School of Public Health (Joseph Margolick); Howard
Brown Health Center and Northwestern University Medical School (John
Phair, Steven Wolinsky); University of California, Los Angeles (Roger
Detels, Oto Martinez-Maza); University of Pittsburgh (Charles Rinaldo);
and Data Analysis Center (Lisa Jacobson). The MACS is funded by the
National Institute of Allergy and Infectious Diseases, with additional
supplemental funding from the National Cancer Institute; and the
National Heart, Lung, and Blood Institute: U01-AI-35042, UL1-RR025005
(GCRC), U01-AI-35043, U01-AI-35039, U01-AI-35040, and U01-AI-35041. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 40
TC 20
Z9 20
U1 3
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7390
EI 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD MAR
PY 2014
VL 10
IS 3
AR e1004196
DI 10.1371/journal.pgen.1004196
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA AI8FM
UT WOS:000337144700026
PM 24603468
ER
PT J
AU Gopal, GJ
Kumar, A
Pal, J
Mukhopadhyay, G
AF Gopal, Gopal Jee
Kumar, Awanish
Pal, Jagannath
Mukhopadhyay, Gauranga
TI Molecular characterization and polyclonal antibody generation against
core component CagX protein of Helicobacter pylori type IV secretion
system
SO BIOENGINEERED
LA English
DT Article
DE H. pylori; Cag-PAI; type IV secretion system; CagX; molecular
characterization
ID PATHOGENICITY ISLAND; VIRULENCE FACTORS; INFECTION; INDUCTION;
TRANSLOCATION; INTERLEUKIN-8; MUTAGENESIS; STRAINS; DISEASE; SURFACE
AB Gram-negative bacteria Helicobacter pylori cause gastric ulcer, duodenal cancer, and found in almost half of the world's residents. The protein responsible for this disease is secreted through type IV secretion system (TFSS) of H. pylori. TFSS is encoded by 40-kb region of chromosomal DNA known as cag-pathogenicity island (PAI). TFSS comprises of three major components: cytoplasmic/inner membrane ATPase, transmembrane core-complex and outer membranous pilli, and associated subunits. Core complex consists of CagX, CagT, CagM, and Cag3(delta) proteins as per existing knowledge. In this study, we have characterized one of the important component of core-complex forming sub-unit protein, i.e., CagX. Complete ORF of CagX except signal peptide coding region was cloned and expressed in pET28a vector. Purification of CagX protein was performed, and polyclonal anti-sera against full-length recombinant CagX were raised in rabbit model. We obtained a very specific and high titer, CagX anti-sera that were utilized to characterize endogenous CagX. Surface localization of CagX was also seen by immunofluorescence microscopy. In short for the first time a full-length CagX was characterized, and we showed that CagX is the part of high molecular weight core complex, which is important for assembly and function of H. pylori TFSS.
C1 [Gopal, Gopal Jee; Pal, Jagannath; Mukhopadhyay, Gauranga] Jawaharlal Nehru Univ, Special Ctr Mol Med, New Delhi 110067, India.
[Gopal, Gopal Jee] Maharaja Sayajirao Univ Baroda, Fac Sci, Dept Biochem, Vadodara, Gujarat, India.
[Kumar, Awanish] Natl Inst Technol, Dept Biotechnol, Raipur, Chhattisgarh, India.
[Pal, Jagannath] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Gopal, GJ (reprint author), Jawaharlal Nehru Univ, Special Ctr Mol Med, New Delhi 110067, India.
EM gopaljigopal@rediffmail.com; garunga@hotmail.com
OI Kumar, Awanish/0000-0001-8735-479X
FU Council for Scientific and Industrial Research (CSIR); University Grant
Commission (UGC), New Delhi, India
FX G.J.G. acknowledges the fellowships from the Council for Scientific and
Industrial Research (CSIR) and University Grant Commission (UGC), New
Delhi, India. Plasmid constructs were a kind gift from Prof Haas
(Max-Planck-Institut fur Biologie, Abteilung Infektionsbiologie,
Tubingen, Germany). The authors are thankful to Jawaharlal Nehru
University, New Delhi, India, M. S. University of Baroda, Vadodara,
Gujarat, India, National Institute of Technology, Raipur (Chhattisgarh),
India. G.J.G. is grateful to Prof. Rakesh Bhatnagar (School of
Biotechnology, Jawaharlal Nehru University [JNU], New Delhi, India) for
providing valuable advice, encouragement, and support.
NR 27
TC 0
Z9 0
U1 1
U2 2
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 2165-5979
EI 2165-5987
J9 BIOENGINEERED
JI Bioengineered
PD MAR-APR
PY 2014
VL 5
IS 2
BP 107
EP 113
DI 10.4161/bioe.27808
PG 7
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA AI5KU
UT WOS:000336906200017
PM 24637488
ER
PT J
AU Garrido, MM
AF Garrido, Melissa M.
TI Propensity Scores and Palliative Care
SO JOURNAL OF PALLIATIVE MEDICINE
LA English
DT Letter
ID MODELS
C1 [Garrido, Melissa M.] James J Peters VA Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA.
[Garrido, Melissa M.] Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, New York, NY USA.
RP Garrido, MM (reprint author), 130 W Kingsbridge Rd,Room 4A-17, Bronx, NY 10468 USA.
EM melissa.garrido@mssm.edu
FU NIA NIH HHS [P30 AG028741]
NR 4
TC 3
Z9 3
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1096-6218
EI 1557-7740
J9 J PALLIAT MED
JI J. Palliat. Med.
PD MAR
PY 2014
VL 17
IS 3
BP 261
EP 261
DI 10.1089/jpm.2013.0587
PG 1
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA AI6ZL
UT WOS:000337027700004
PM 24517275
ER
PT J
AU Goebel, JR
Ahluwalia, SC
Chong, K
Shreve, ST
Goldzweig, CL
Austin, C
Asch, SM
Lorenz, KA
AF Goebel, Joy R.
Ahluwalia, Sangeeta C.
Chong, Kelly
Shreve, Scott T.
Goldzweig, Caroline L.
Austin, Colletta
Asch, Steven M.
Lorenz, Karl A.
TI Developing an Informatics Tool To Advance Supportive Care: The Veterans
Health Care Administration Palliative Care National Clinical Template
SO JOURNAL OF PALLIATIVE MEDICINE
LA English
DT Article
ID SET
AB Background: Increasing emphasis in performance-based payment, public reporting, and quality improvement (QI) has led to widespread interest in measuring and improving the quality of care. By 2014, hospice programs will be required to report quality data to the federal government or incur financial penalties. With this increased interest in quality reporting comes an opportunity to develop informatics tools to capture data that reflect the complex practices involved in palliative care (PC). Therefore, there is a need to disseminate information on developing tools that facilitate capturing data and fostering improved performance. The Veterans Health Care Administration, a national leader in health information technology (HIT) and PC, established the Quality Improvement Resource Center (QuIRC) to develop innovative HIT tools to standardize and improve PC practices throughout the 153 Department of Veterans Affairs (VA) medical centers nationwide.
Objective: The aim of the paper is to describe the development of the Palliative Care-National Clinical Template (PC-NCT) for documenting initial PC consults.
Results: Domains of quality of life provided the foundation for this template. Principles of user-centered informatics design guided development activities. A national consensus panel of PC experts prioritized quality indicators as targets for QI. An interdisciplinary team of PC providers identified desired aspects of template functionality. QuIRC balanced PC providers' desired aspects of functionality against the feasibility within the VA HIT system. Formal pilot and usability testing contributed to numerous iterations of the PC-NCT currently piloted in five geographically distributed sites.
Conclusion: This paper presents a robust approach to developing an informatics tool for PC practice. Data collected via the PC-NCT will bring variations in current practice into view and assist in directing resources at "important targets'' for QI. Although the development of HIT tools to quantify PC practice is complex, there is enormous potential to improve the quality of care for patients and families facing serious illnesses.
C1 [Goebel, Joy R.] Calif State Univ Long Beach, Sch Nursing, Long Beach, CA 90804 USA.
[Ahluwalia, Sangeeta C.] Oregon State Univ, Sch Social & Behav Hlth Sci, Corvallis, OR 97331 USA.
[Chong, Kelly; Lorenz, Karl A.] Greater Los Angeles VA Hlth Care Syst, Qual Improvement Resource Ctr, Los Angeles, CA USA.
[Shreve, Scott T.] Lebanon VA Hlth Care Syst, Hosp & Palliat Care, Lebanon, PA USA.
[Shreve, Scott T.] Penn State Coll Med, Lebanon, PA USA.
[Goldzweig, Caroline L.; Austin, Colletta] Greater Los Angeles VA Hlth Care Syst, Clin Informat, Los Angeles, CA USA.
[Asch, Steven M.] Palo Alto VA Hlth Care Syst, Palo Alto, CA USA.
[Asch, Steven M.] Stanford Univ, Div Gen Med Disciplines, Palo Alto, CA 94304 USA.
[Lorenz, Karl A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
RP Goebel, JR (reprint author), Calif State Univ Long Beach, Sch Nursing, 1250 Bellflower Blvd, Long Beach, CA 90804 USA.
EM joy.goebel@csulb.edu
NR 19
TC 0
Z9 0
U1 0
U2 6
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1096-6218
EI 1557-7740
J9 J PALLIAT MED
JI J. Palliat. Med.
PD MAR
PY 2014
VL 17
IS 3
BP 266
EP 273
DI 10.1089/jpm.2013.0288
PG 8
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA AI6ZL
UT WOS:000337027700007
PM 24548178
ER
PT J
AU Pollock, CB
McDonough, S
Wang, VS
Lee, H
Ringer, L
Li, X
Prandi, C
Lee, RJ
Feldman, AS
Koltai, H
Kapulnik, Y
Rodriguez, OC
Schlegel, R
Albanese, C
Yarden, RI
AF Pollock, Claire B.
McDonough, Sara
Wang, Victor S.
Lee, Hyojung
Ringer, Lymor
Li, Xin
Prandi, Cristina
Lee, Richard J.
Feldman, Adam S.
Koltai, Hinanit
Kapulnik, Yoram
Rodriguez, Olga C.
Schlegel, Richard
Albanese, Christopher
Yarden, Ronit I.
TI Strigolactone analogues induce apoptosis through activation of p38 and
the stress response pathway in cancer cell lines and in conditionally
reprogrammed primary prostate cancer cells
SO ONCOTARGET
LA English
DT Article
DE Plant hormone; cell cycle arrest; apoptosis; stress response; p38-MAPK
ID FOXO TRANSCRIPTION FACTOR; PROTEIN-KINASE; HEPATOCELLULAR-CARCINOMA;
METHYL JASMONATE; EPITHELIAL-CELLS; MAPK PATHWAYS; PROLIFERATION;
ARREST; JNK; P38-ALPHA
AB Strigolactones are a novel class of plant hormones produced in roots and regulate shoot and root development. We have previously shown that synthetic strigolactone analogues potently inhibit growth of breast cancer cells and breast cancer stem cells. Here we show that strigolactone analogues inhibit the growth and survival of an array of cancer-derived cell lines representing solid and non-solid cancer cells including: prostate, colon, lung, melanoma, osteosarcoma and leukemic cell lines, while normal cells were minimally affected. Treatment of cancer cells with strigolactone analogues was hallmarked by activation of the stress-related MAPKs: p38 and JNK and induction of stress-related genes; cell cycle arrest and apoptosis evident by increased percentages of cells in the sub-G1 fraction and Annexin V staining. In addition, we tested the response of patient-matched conditionally reprogrammed primary prostate normal and cancer cells. The tumor cells exhibited significantly higher sensitivity to the two most potent SL analogues with increased apoptosis confirmed by PARP1 cleavage compared to their normal counterpart cells. Thus, Strigolactone analogues are promising candidates for anticancer therapy by their ability to specifically induce cell cycle arrest, cellular stress and apoptosis in tumor cells with minimal effects on growth and survival of normal cells.
C1 [Pollock, Claire B.; McDonough, Sara; Wang, Victor S.; Lee, Hyojung; Yarden, Ronit I.] Georgetown Univ, Med Ctr, Dept Human Sci, Washington, DC 20057 USA.
[Pollock, Claire B.; Ringer, Lymor; Rodriguez, Olga C.; Schlegel, Richard; Albanese, Christopher; Yarden, Ronit I.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC USA.
[Ringer, Lymor; Rodriguez, Olga C.; Schlegel, Richard; Albanese, Christopher] Georgetown Univ, Med Ctr, Dept Pathol, Washington, DC USA.
[Ringer, Lymor; Rodriguez, Olga C.; Schlegel, Richard; Albanese, Christopher] Georgetown Univ, Med Ctr, Ctr Cellular Reprogramming, Washington, DC USA.
[Li, Xin] Georgetown Univ, Med Ctr, Dept Biostat Bioinformat & Biomath, Washington, DC USA.
[Prandi, Cristina] Univ Turin, Dept Chem, Turin, Italy.
[Lee, Richard J.; Feldman, Adam S.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Koltai, Hinanit] Agr Res Org, Dept Ornamental Hort, IL-50250 Bet Dagan, Israel.
[Kapulnik, Yoram] Agr Res Org, Dept Field Crops, IL-50250 Bet Dagan, Israel.
[Kapulnik, Yoram] Agr Res Org, Nat Resources Inst Plant Sci, IL-50250 Bet Dagan, Israel.
RP Yarden, RI (reprint author), Georgetown Univ, Med Ctr, Dept Human Sci, Washington, DC 20057 USA.
EM riy2@georgetown.edu
RI prandi, cristina/L-9290-2015
OI prandi, cristina/0000-0001-9510-8783
FU NIH/NCI grant [P30-CA051008]; Department of Defense Breast Program
[W81XWH-11-1-0190]; BioBits Project, Regione Piemonte, Italy; SLEP
(Signaling Role of Strigolactones at the interface between plants,
microorganisms and the Environment); DOD pre-doctoral grant [PC101946,
R01 CA129003, DOD PCRP SIDA W81XWH-13-1-0327]; CTSA pilot award
FX We gratefully thank Drs. Rebecca Riggins, York Tomita and Michael
Johnson (Lombardi Comprehensive Cancer Centre) for sharing reagents and
helpful discussions. We would also like to thank Allison Hall for her
technical assistance. Technical services were provided by the Flow
Cytometry & Cell Sorting, Genomics and Epigenomics and Tissue Culture
Shared Resources Shared Resources which are partially supported by
NIH/NCI grant P30-CA051008.; This work was supported by the Department
of Defense Breast Program W81XWH-11-1-0190 (RIY) and by the BioBits
Project, Regione Piemonte, Italy (CP), by the SLEP (Signaling Role of
Strigolactones at the interface between plants, microorganisms and the
Environment) (CP), by a DOD pre-doctoral grant PC101946 (LR), an R01
CA129003 (CA), a DOD PCRP SIDA W81XWH-13-1-0327 (CA) and CTSA pilot
award (CA).
NR 43
TC 15
Z9 15
U1 1
U2 24
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD MAR
PY 2014
VL 5
IS 6
BP 1683
EP 1698
PG 16
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA AI6EO
UT WOS:000336964000023
PM 24742967
ER
PT J
AU Singh, S
Petrovic, D
Jamnik, E
Aran, S
Pourjabbar, S
Kave, ML
Bradley, SE
Choy, G
Kalra, MK
AF Singh, Sarabjeet
Petrovic, Dean
Jamnik, Ethen
Aran, Shima
Pourjabbar, Sarvenaz
Kave, Maggie L.
Bradley, Stephen E.
Choy, Garry
Kalra, Mannudeep K.
TI Effect of Localizer Radiograph on Radiation Dose Associated With
Automatic Exposure Control: Human Cadaver and Patient Study
SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY
LA English
DT Article
DE automatic exposure control; radiation dose reduction; CT localizer
radiograph; tube current modulation
ID TUBE CURRENT MODULATION; Z-AXIS MODULATION; COMPUTED-TOMOGRAPHY; CT;
REDUCTION; SYSTEMS; OPTIMIZATION; ABDOMEN; PELVIS
AB Purpose: To evaluate the effect of localizing radiograph on computed tomography (CT) radiation dose associated with automatic exposure control with a human cadaver and patient study.
Materials and Methods: Institutional review board approved the study with a waiver of informed consent. Two chest CT image series with fixed tube current and combined longitudinal-angular automatic exposure control (AEC) were acquired in a human cadaver (64-year-old man) after each of the 8 combinations of localizer radiographs (anteroposterior [AP], AP lateral, AP-posteroanterior [PA], lateral AP, lateral PA, PA, PA-AP, and PA lateral). Applied effective milliampere second, volume CT dose index (CTDIvol) and image noise were recorded for all 24-image series. Volume CT dose indexes were also recorded in 20 patients undergoing chest and abdominal CT after PA and PA-lateral radiographs with the use of AEC. Data were analyzed using analysis of variance and linear correlation tests.
Results: With AEC, the CTDIvol fluctuates with the number and projection of localizer radiographs (P < 0.0001). Lowest CTDIvol values are seen when 2 orthogonal localizer radiographs are acquired, whereas highest values are seen when single PA or AP-PA projection localizer radiographs are acquired for planning (P < 0.0001). In 20 patients, CT scanning with AEC after acquisition of 2 orthogonal projection localizer radiographs was associated with significant reduction in radiation dose compared to PA projection radiographs alone (P < 0.0001).
Conclusions: When scanning with AEC, acquisition of 2 orthogonal localizer radiographs is associated with lower CTDIvol compared to a single localizer radiograph.
C1 [Singh, Sarabjeet; Aran, Shima; Pourjabbar, Sarvenaz; Kave, Maggie L.; Bradley, Stephen E.; Choy, Garry; Kalra, Mannudeep K.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Petrovic, Dean; Jamnik, Ethen] Univ Ljubljana, Dept Radiol, Med Ctr, Ljubljana, Slovenia.
RP Singh, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
EM ssingh6@partners.org
FU Radiological Society of North America (RSNA) Research and Education
Foundation's Education Scholar Grant
FX This study was supported in part by Radiological Society of North
America (RSNA) Research and Education Foundation's Education Scholar
Grant to one of the coauthors (MKK). The data were available to all
coauthors throughout the course of the study and manuscript preparation.
NR 16
TC 6
Z9 6
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0363-8715
EI 1532-3145
J9 J COMPUT ASSIST TOMO
JI J. Comput. Assist. Tomogr.
PD MAR-APR
PY 2014
VL 38
IS 2
BP 293
EP 298
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AI2YZ
UT WOS:000336726400025
PM 24632938
ER
PT J
AU Butros, SR
DelCarmen, MG
Uppot, RN
Arellano, RS
AF Butros, Selim R.
DelCarmen, Marcela G.
Uppot, Raul N.
Arellano, Ronald S.
TI Image-Guided Percutaneous Thermal Ablation of Metastatic Pelvic Tumor
From Gynecologic Malignancies
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID RADIOFREQUENCY ABLATION; HEPATOCELLULAR-CARCINOMA; WATER
AB BACKGROUND: Image-guided percutaneous thermal ablation is a commonly performed therapeutic procedure for various tumors. Thermal ablation is not frequently used in the pelvis as a result of anatomic concerns and the potential risk of nontarget tissue injury.
TECHNIQUE: Percutaneous thermal ablation is a minimally invasive procedure involving special probes inserted through the skin to the target lesion under imaging guidance. Various delivery methods of thermal ablation exist, including radiofrequency ablation, which burns tissue, and cryoablation, which freezes tissue with an ultimate goal to destroy the target tumor while minimizing damage to adjacent structures. Protective measures can be used to provide access and safe treatment delivery such as pyeloperfusion to protect the ureter with the infusion of water using a ureteral stent or hydrodissection to protect adjacent structures by displacing them away with the infusion of water using percutaneously placed needles.
EXPERIENCE: The authors' experience with the technique involves thermal ablation of recurrent pelvic tumor in three patients with various gynecologic malignancies who each had a single focus of pelvic recurrence after surgical resection and radiation treatment. No residual or recurrent disease was seen at the treatment site on follow-up imaging consistent with local tumor control.
CONCLUSION: Thermal ablation of metastatic or recurrent pelvic tumor is technically feasible and should be considered in selected patients with no treatment alternative.
C1 [Butros, Selim R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Abdominal Imaging & Intervent, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA.
RP Butros, SR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA.
EM sbutros@partners.org
NR 9
TC 2
Z9 3
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
EI 1873-233X
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD MAR
PY 2014
VL 123
IS 3
BP 500
EP 505
DI 10.1097/AOG.0000000000000133
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA AI4BA
UT WOS:000336809100004
PM 24499747
ER
PT J
AU Hung, KJ
Tsai, AC
Johnson, TRB
Walensky, RP
Bangsberg, DR
Kerry, VB
AF Hung, Kristin J.
Tsai, Alexander C.
Johnson, Timothy R. B.
Walensky, Rochelle P.
Bangsberg, David R.
Kerry, Vanessa B.
TI Scope of Global Health Training in US Obstetrics and Gynecology
Residency Programs In Reply
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Letter
C1 [Hung, Kristin J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Tsai, Alexander C.; Walensky, Rochelle P.; Bangsberg, David R.; Kerry, Vanessa B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Tsai, Alexander C.; Walensky, Rochelle P.; Bangsberg, David R.; Kerry, Vanessa B.] Harvard Univ, Sch Med, Boston, MA USA.
[Johnson, Timothy R. B.] Univ Michigan, Ann Arbor, MI 48109 USA.
RP Hung, KJ (reprint author), Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
RI yan, liu/A-1822-2015
OI yan, liu/0000-0001-8517-1084
FU NIAID NIH HHS [R01 AI093269]; NIMH NIH HHS [K23 MH096620]
NR 6
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
EI 1873-233X
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD MAR
PY 2014
VL 123
IS 3
BP 666
EP 667
PG 4
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA AI4BA
UT WOS:000336809100032
PM 24553159
ER
PT J
AU Brent, BK
Coombs, G
Keshavan, MS
Seidman, LJ
Moran, JM
Holt, DJ
AF Brent, Benjamin K.
Coombs, Garth
Keshavan, Matcheri S.
Seidman, Larry J.
Moran, Joseph M.
Holt, Daphne J.
TI Subclinical delusional thinking predicts lateral temporal cortex
responses during social reflection
SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE
LA English
DT Article
DE delusions; psychosis; fMRI; lateral temporal cortex; default mode
network
ID MEDIAL PREFRONTAL CORTEX; DEFAULT-MODE NETWORK; SELF-REFLECTION;
BRAIN-FUNCTION; FUNCTIONAL CONNECTIVITY; PERSECUTORY DELUSIONS;
METACOGNITIVE EVALUATION; SCHIZOPHRENIC-PATIENTS; PSYCHOSIS PRONENESS;
REALITY DISTORTION
AB Neuroimaging studies have demonstrated associations between delusions in psychotic disorders and abnormalities of brain areas involved in social cognition, including medial prefrontal cortex (MPFC), posterior cingulate cortex, and lateral temporal cortex (LTC). General population studies have linked subclinical delusional thinking to impaired social cognition, raising the question of whether a specific pattern of brain activity during social perception is associated with delusional beliefs. Here, we tested the hypothesis that subclinical delusional thinking is associated with changes in neural function, while subjects made judgments about themselves or others ['social reflection' (SR)]. Neural responses during SR and non-social tasks, as well as resting-state activity, were measured using functional magnetic resonance imaging in 22 healthy subjects. Delusional thinking was measured using the Peters et al. Delusions Inventory. Delusional thinking was negatively correlated with responses of the left LTC during SR (r = -0.61, P = 0.02, Bonferroni corrected), and connectivity between the left LTC and left ventral MPFC, and was positively correlated with connectivity between the left LTC and the right middle frontal and inferior temporal cortices. Thus, delusional thinking in the general population may be associated with reduced activity and aberrant functional connectivity of cortical areas involved in SR.
C1 [Brent, Benjamin K.; Keshavan, Matcheri S.; Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
[Coombs, Garth; Holt, Daphne J.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02114 USA.
[Coombs, Garth; Seidman, Larry J.; Holt, Daphne J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA.
[Moran, Joseph M.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA.
RP Holt, DJ (reprint author), 149 13th St, Charlestown, MA 02129 USA.
EM dholt@partners.org
FU Harvard Medical School; National Institute of Mental Health
[K23MH076054]; National Alliance for Research on Depression and
Schizophrenia; Sidney R. Baer, Jr Foundation; Commonwealth Research
Center of Massachusetts [SCDMH82101008006]
FX We thank the Harvard Catalyst and Dr Heidi Thermenos for valuable
statistical support throughout the study. This study was supported by
Harvard Medical School's Stuart T. Hauser Clinical Research Training
Program (B.K.B.) and Peter B. Livingston Fellowship (B.K.B.), the
National Institute of Mental Health K23MH076054 (D.J.H.), the National
Alliance for Research on Depression and Schizophrenia with the Sidney R.
Baer, Jr Foundation (D.J.H.), and the Commonwealth Research Center of
Massachusetts SCDMH82101008006 (L.J.S.).
NR 93
TC 7
Z9 7
U1 2
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1749-5016
EI 1749-5024
J9 SOC COGN AFFECT NEUR
JI Soc. Cogn. Affect. Neurosci.
PD MAR
PY 2014
VL 9
IS 3
BP 273
EP 282
DI 10.1093/scan/nss129
PG 10
WC Neurosciences; Psychology; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA AH9UG
UT WOS:000336488300003
PM 23160817
ER
PT J
AU Todd, JN
Florez, JC
AF Todd, Jennifer N.
Florez, Jose C.
TI An update on the pharmacogenomics of metformin: progress, problems and
potential
SO PHARMACOGENOMICS
LA English
DT Article
DE antidiabetic; biguanide; metformin; pharmacogenetics; Type 2 diabetes
mellitus
ID ORGANIC CATION TRANSPORTER; POLYCYSTIC-OVARY-SYNDROME; ACTIVATED
PROTEIN-KINASE; GENETIC-VARIATION; DIABETES-MELLITUS;
FUNCTIONAL-CHARACTERIZATION; RESPIRATORY-CHAIN; RENAL CLEARANCE;
VARIANTS; POLYMORPHISMS
AB The increasing prevalence of Type 2 diabetes has emphasized the need to optimize treatment regimens. Metformin, the most widely used oral agent, is recommended as first-line drug therapy by multiple professional organizations. Response to metformin varies significantly at the individual level; this heterogeneity may be explained in part by genetic factors. Understanding these underlying factors may aid with tailoring treatment for individual patients as well as with designing improved Type 2 diabetes therapies. The past 10 years have seen substantial progress in the understanding of the pharmacogenetics of metformin response. The majority of this work has focused on genes involved in the pharmacokinetics of metformin. Owing to the uncertainty surrounding its mechanism of action, studies of pharmacodynamic genetics have been relatively few; genome-wide approaches have the potential to illuminate the molecular details of metformin response. In this review we summarize current knowledge about metformin pharmacogenetics and suggest directions for future investigation.
C1 [Todd, Jennifer N.] Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Todd, Jennifer N.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA.
[Todd, Jennifer N.; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Todd, Jennifer N.; Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA.
[Florez, Jose C.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA.
RP Florez, JC (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA.
EM jcflorez@partners.org
FU NIH [T32 DK007260]; National Institute of Diabetes and Digestive and
Kidney Diseases [R01 DK072041, R01 DK088214]; Massachusetts General
Hospital Scholars Award
FX JN Todd is supported by NIH Training Grant T32 DK007260. JC Florez is
supported by National Institute of Diabetes and Digestive and Kidney
Diseases grants R01 DK072041 and R01 DK088214 and a Massachusetts
General Hospital Scholars Award. 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 58
TC 12
Z9 13
U1 0
U2 13
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 MAR
PY 2014
VL 15
IS 4
BP 529
EP 539
DI 10.2217/PGS.14.21
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AC7IA
UT WOS:000332700200020
PM 24624919
ER
PT J
AU Atri, A
Tocco, M
Hendrix, S
Pejovic, V
Graham, SM
AF Atri, Alireza
Tocco, Michael
Hendrix, Suzanne
Pejovic, Vojislav
Graham, Stephen M.
TI Cumulative Benefits of Extended-Release Memantine (28 mg, Once Daily)
Across Clinical Domains in Patients With Moderate to Severe Alzheimer's
Disease: An Area Under the Curve Analysis
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
(AAGP)
CY MAR, 2014
CL Orlando, FL
SP Amer Assoc Geriatr Psychiat
C1 [Atri, Alireza] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Atri, Alireza] Harvard Univ, Sch Med, Boston, MA USA.
[Tocco, Michael; Graham, Stephen M.] Forest Res Inst, Jersey City, NJ USA.
[Hendrix, Suzanne] Pentara Corp, Salt Lake City, UT USA.
[Pejovic, Vojislav] Prescott Med Commun Grp, Chicago, IL USA.
NR 0
TC 1
Z9 1
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2014
VL 22
IS 3
SU S
BP S120
EP S121
PG 2
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA AH4FE
UT WOS:000336081800130
ER
PT J
AU Beristianos, M
Yaffe, K
Cohen, B
Byers, AL
AF Beristianos, Matthew
Yaffe, Kristine
Cohen, Beth
Byers, Amy L.
TI The Impact of Late-Life PTSD on Vascular-Related Disorders
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
(AAGP)
CY MAR, 2014
CL Orlando, FL
SP Amer Assoc Geriatr Psychiat
C1 [Beristianos, Matthew; Yaffe, Kristine; Cohen, Beth; Byers, Amy L.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Beristianos, Matthew; Yaffe, Kristine; Cohen, Beth; Byers, Amy L.] San Francisco VA Med Ctr, San Francisco, CA USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2014
VL 22
IS 3
SU S
BP S55
EP S55
PG 1
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA AH4FE
UT WOS:000336081800049
ER
PT J
AU Byers, AL
AF Byers, Amy L.
TI Suicidal Behavior in Racially and Ethnically Diverse Older Americans
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
(AAGP)
CY MAR, 2014
CL Orlando, FL
SP Amer Assoc Geriatr Psychiat
C1 [Byers, Amy L.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Byers, Amy L.] San Francisco VA Med Ctr, San Francisco, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2014
VL 22
IS 3
SU S
BP S125
EP S125
PG 1
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA AH4FE
UT WOS:000336081800137
ER
PT J
AU Epstein-Lubow, G
Boland, R
Cheong, JA
Llorente, MD
AF Epstein-Lubow, Gary
Boland, Robert
Cheong, Josepha A.
Llorente, Maria D.
TI TRAINING PSYCHIATRY RESIDENTS AND FELLOWS IN QUALITY IMPROVEMENT:
GERIATRIC PSYCHIATRY CAN HELP LEAD THE WAY
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
(AAGP)
CY MAR, 2014
CL Orlando, FL
SP Amer Assoc Geriatr Psychiat
C1 [Epstein-Lubow, Gary; Boland, Robert] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA.
[Cheong, Josepha A.] Univ Florida, Coll Med, Gainesville, FL USA.
[Llorente, Maria D.] US Dept Vet Affairs, Washington, DC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2014
VL 22
IS 3
SU S
BP S34
EP S35
PG 2
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA AH4FE
UT WOS:000336081800044
ER
PT J
AU Fries, AE
Leong, S
Benson, A
Streim, JE
DiFilippo, S
Oslin, DW
AF Fries, Allison E.
Leong, Shirley
Benson, Amy
Streim, Joel E.
DiFilippo, Suzanne
Oslin, David W.
TI Suicidal ideation and health outcomes in an 'old-old' population
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
(AAGP)
CY MAR, 2014
CL Orlando, FL
SP Amer Assoc Geriatr Psychiat
C1 [Fries, Allison E.; Leong, Shirley; Benson, Amy; Streim, Joel E.; DiFilippo, Suzanne; Oslin, David W.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Leong, Shirley; Benson, Amy; Streim, Joel E.; DiFilippo, Suzanne; Oslin, David W.] Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr VISN4, Philadelphia, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2014
VL 22
IS 3
SU S
BP S61
EP S62
PG 2
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA AH4FE
UT WOS:000336081800057
ER
PT J
AU Gatchel, JR
Jordan-Arthur, B
Lewandowski, KE
McCabe, CF
Harper, DG
Forester, B
AF Gatchel, Jennifer R.
Jordan-Arthur, Brittany
Lewandowski, Kathryn E.
McCabe, Cara F.
Harper, David G.
Forester, Brent
TI Neuropsychological Function and Predictors of Cognitive Impairment in
Geriatric Mood Disorders
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
(AAGP)
CY MAR, 2014
CL Orlando, FL
SP Amer Assoc Geriatr Psychiat
C1 [Gatchel, Jennifer R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Gatchel, Jennifer R.; Jordan-Arthur, Brittany; Lewandowski, Kathryn E.; McCabe, Cara F.; Harper, David G.; Forester, Brent] McLean Hosp, Belmont, MA 02178 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2014
VL 22
IS 3
SU S
BP S64
EP S65
PG 2
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA AH4FE
UT WOS:000336081800061
ER
PT J
AU Haratz, J
Zimmerman, J
Leong, S
Helstrom, A
Benson, A
DiFilippo, S
Streim, JE
Oslin, DW
AF Haratz, Josh
Zimmerman, Jacob
Leong, Shirley
Helstrom, Amy
Benson, Amy
DiFilippo, Suzanne
Streim, Joel E.
Oslin, David W.
TI A telephone-based intervention for chronic pain in older adults enrolled
in a behavioral health care management program
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
(AAGP)
CY MAR, 2014
CL Orlando, FL
SP Amer Assoc Geriatr Psychiat
C1 [Haratz, Josh] Drexel Univ Coll Med, Philadelphia, PA USA.
[Zimmerman, Jacob; Leong, Shirley; Helstrom, Amy; Benson, Amy; DiFilippo, Suzanne; Streim, Joel E.; Oslin, David W.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Leong, Shirley; Helstrom, Amy; Benson, Amy; DiFilippo, Suzanne; Streim, Joel E.; Oslin, David W.] Philadelphia VA Med Ctr, VISN4 Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2014
VL 22
IS 3
SU S
BP S103
EP S104
PG 2
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA AH4FE
UT WOS:000336081800111
ER
PT J
AU Kasckow, J
Harvey, PD
Cohen, CI
Rajii, T
AF Kasckow, John
Harvey, Philip D.
Cohen, Carl I.
Rajii, Tarek
TI COGNITION AND FUNCTIONING IN OLDER PATIENTS WITH SCHIZOPHRENIA: RECENT
RESEARCH
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
(AAGP)
CY MAR, 2014
CL Orlando, FL
SP Amer Assoc Geriatr Psychiat
C1 [Kasckow, John] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
[Kasckow, John] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA.
[Cohen, Carl I.] SUNY Downstate, Brooklyn, NY USA.
[Harvey, Philip D.] Univ Miami, Miami, FL USA.
[Rajii, Tarek] Univ Toronto, Toronto, ON, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2014
VL 22
IS 3
SU S
BP S8
EP S8
PG 1
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA AH4FE
UT WOS:000336081800006
ER
PT J
AU Liptzin, B
Streim, JE
Colenda, CC
AF Liptzin, Benjamin
Streim, Joel E.
Colenda, Christopher C.
TI THE GERIATRIC PSYCHIATRIST AS FAMILY CAREGIVER: LESSONS LEARNED
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
(AAGP)
CY MAR, 2014
CL Orlando, FL
SP Amer Assoc Geriatr Psychiat
C1 [Liptzin, Benjamin] Baystate Med Ctr, Springfield, MA USA.
[Liptzin, Benjamin] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Colenda, Christopher C.] W Virginia Univ, Robert C Byrd Hlth Sci Ctr, Morgantown, WV 26506 USA.
[Streim, Joel E.] Univ Penn, Sch Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Streim, Joel E.] Philadelphia VA Med Ctr, Philadelphia, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2014
VL 22
IS 3
SU S
BP S33
EP S33
PG 1
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA AH4FE
UT WOS:000336081800042
ER
PT J
AU Mathur, N
Leong, S
DiLeone, BA
Casares, J
Streim, JE
Oslin, DW
DiFilippo, S
AF Mathur, Nivedita
Leong, Shirley
DiLeone, Brooke A.
Casares, Jose
Streim, Joel E.
Oslin, David W.
DiFilippo, Suzanne
TI Disparity in Antidepressant Prescription between African American and
Caucasian Elderly Veterans: A Retrospective Descriptive Study
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
(AAGP)
CY MAR, 2014
CL Orlando, FL
SP Amer Assoc Geriatr Psychiat
C1 [Mathur, Nivedita; Streim, Joel E.; Oslin, David W.; DiFilippo, Suzanne] Univ Penn, Philadelphia, PA 19104 USA.
[Mathur, Nivedita; Leong, Shirley; DiLeone, Brooke A.; Casares, Jose; Streim, Joel E.; Oslin, David W.; DiFilippo, Suzanne] Philadelphia VA Med Ctr, Philadelphia, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2014
VL 22
IS 3
SU S
BP S90
EP S91
PG 2
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA AH4FE
UT WOS:000336081800097
ER
PT J
AU Mintzer, J
Steinberg, E
AF Mintzer, Jacobo
Steinberg, Ellen
TI Elder courts: transforming a crisis into a therapeutic opportunity
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
(AAGP)
CY MAR, 2014
CL Orlando, FL
SP Amer Assoc Geriatr Psychiat
C1 [Steinberg, Ellen] Charleston Cty Magistrate Court, Charleston, SC USA.
[Mintzer, Jacobo] Roper St Francis Healthcare, Charleston, SC USA.
[Mintzer, Jacobo] Med Univ S Carolina, Charleston, SC 29425 USA.
[Mintzer, Jacobo] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
NR 0
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 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2014
VL 22
IS 3
SU S
BP S143
EP S143
PG 1
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA AH4FE
UT WOS:000336081800160
ER
PT J
AU Streim, JE
Boustani, M
Unutzer, J
Oslin, DW
AF Streim, Joel E.
Boustani, Malaz
Unutzer, Jurgen
Oslin, David W.
TI IMPLEMENTATION OF INTEGRATED COLLABORATIVE GERIATRIC MENTAL HEALTH CARE
MODELS: WHAT HAVE WE LEARNED FROM A DECADE OF EXPERIENCE?
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
(AAGP)
CY MAR, 2014
CL Orlando, FL
SP Amer Assoc Geriatr Psychiat
C1 [Streim, Joel E.; Oslin, David W.] Univ Penn, Philadelphia, PA 19104 USA.
[Streim, Joel E.; Oslin, David W.] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Boustani, Malaz] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Unutzer, Jurgen] Univ Washington, Sch Med, Seattle, WA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2014
VL 22
IS 3
SU S
BP S18
EP S18
PG 1
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA AH4FE
UT WOS:000336081800020
ER
PT J
AU Streim, JE
Liptzin, B
Chung, H
Rosen, J
AF Streim, Joel E.
Liptzin, Benjamin
Chung, Henry
Rosen, Jules
TI EARLY EXPERIENCES WITH IMPLEMENTATION OF ACCOUNTABLE CARE ORGANIZATIONS
(ACOS): HOW ARE GERIATRIC MENTAL HEALTH SERVICES PROVIDED?
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
(AAGP)
CY MAR, 2014
CL Orlando, FL
SP Amer Assoc Geriatr Psychiat
C1 [Streim, Joel E.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Streim, Joel E.] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Liptzin, Benjamin] Baystate Med Ctr, Springfield, MA USA.
[Liptzin, Benjamin] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Chung, Henry] Albert Einstein Coll Med, New York, NY USA.
[Chung, Henry] Montefiore Care Management Co, New York, NY USA.
[Rosen, Jules] Univ Colorado, Sch Med, Denver, CO 80202 USA.
[Rosen, Jules] Colorado West Mental Hlth, Frisco, CO USA.
NR 0
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 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2014
VL 22
IS 3
SU S
BP S12
EP S13
PG 2
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA AH4FE
UT WOS:000336081800012
ER
PT J
AU Wang, LY
Murphy, RR
Robinson, G
Fredrickson, KR
Thielke, SM
Tsuang, DW
Borson, S
AF Wang, Lucy Y.
Murphy, Richard R.
Robinson, Gayle
Fredrickson, Kristine R.
Thielke, Stephen M.
Tsuang, Debby W.
Borson, Soo
TI Telemedicine Adaptation of a Dementia Care Shared Medical Visit Model
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
(AAGP)
CY MAR, 2014
CL Orlando, FL
SP Amer Assoc Geriatr Psychiat
C1 [Wang, Lucy Y.; Murphy, Richard R.] VA Puget Sound Hlth Care Syst, MIRECC, Seattle, WA USA.
[Wang, Lucy Y.; Thielke, Stephen M.; Tsuang, Debby W.; Borson, Soo] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Murphy, Richard R.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA.
[Robinson, Gayle; Fredrickson, Kristine R.; Thielke, Stephen M.; Tsuang, Debby W.] VA Puget Sound Hlth Care Syst, GRECC, Seattle, WA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2014
VL 22
IS 3
SU S
BP S128
EP S128
PG 1
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA AH4FE
UT WOS:000336081800141
ER
PT J
AU Wiechers, I
Ruderman, L
Levy, I
AF Wiechers, Ilse
Ruderman, Lital
Levy, Ifat
TI Does Patient Age Affect Physician Decision Making Under Varying Risk and
Ambiguity?
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Association-for-Geriatric-Psychiatry
(AAGP)
CY MAR, 2014
CL Orlando, FL
SP Amer Assoc Geriatr Psychiat
C1 [Wiechers, Ilse] Yale Univ, Sch Med, US Dept Vet Affairs, RWJF Clin Scholars Program, New Haven, CT USA.
[Ruderman, Lital; Levy, Ifat] Yale Univ, Sch Med, New Haven, CT USA.
[Levy, Ifat] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD MAR
PY 2014
VL 22
IS 3
SU S
BP S98
EP S98
PG 1
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA AH4FE
UT WOS:000336081800106
ER
PT J
AU Ghobrial, IM
Witzig, TE
Gertz, M
LaPlant, B
Hayman, S
Camoriano, J
Lacy, M
Bergsagel, PL
Chuma, S
DeAngelo, D
Treon, SP
AF Ghobrial, Irene M.
Witzig, Thomas E.
Gertz, Morie
LaPlant, Betsy
Hayman, Suzanne
Camoriano, John
Lacy, Martha
Bergsagel, P. Leif
Chuma, Stacey
DeAngelo, Daniel
Treon, Steven P.
TI Long-term results of the phase II trial of the oral mTOR inhibitor
everolimus (RAD001) in relapsed or refractory Waldenstrom
Macroglobulinemia
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID MULTIPLE-MYELOMA CELLS; CONSENSUS PANEL RECOMMENDATIONS; EXTENDED
RITUXIMAB THERAPY; 2ND INTERNATIONAL WORKSHOP; MAMMALIAN TARGET;
SYNERGISTIC ACTIVITY; CANCER-THERAPY; MYD88 L265P; RAPAMYCIN; UPDATE
AB Everolimus is an oral raptor mTOR inhibitor and has shown activity in patients with Waldenstrom's macroglobulinemia (WM). This study examines a large cohort of patients with relapsed/refractory WM with long-term follow up for survival. Patients were eligible if they had measurable disease, a platelet count > 75,000 x 10(6)/L, an absolute neutrophil count > 1,000 x 10(6)/L. Patients received everolimus 10 mg PO daily and were evaluated monthly. A success was defined as a complete or partial response (PR); minor responses (MR) were recorded and considered to be of clinical benefit. Sixty patients were enrolled and treated. The overall response rate (ORR) was 50% (all PR); the clinical benefit rate including MR or better was 73% (95% CI: 60-84%) with 23% MR. The median time to response for patients who achieved PR was 2 months (range, 1-26). The median duration of response has not been reached and median progression-free survival (PFS) was 21 months. Grade 3 or higher toxicities (at least possibly related to everolimus) were observed in 67% of patients. The most common grade 3 or 4 toxicities were anemia (27%), leukopenia (22%), and thrombocytopenia (20%). Other nonhematological toxicities were diarrhea (5%), fatigue (8%), stomatitis (8%) and pulmonary toxicity (5%). Everolimus has a high single-agent activity of 73% including MR, with a progression free survival of 21 months, indicating that this agent is active in relapsed/refractory WM. Am. J. Hematol. 89:237-242, 2014. (c) 2013 Wiley Periodicals, Inc
C1 [Ghobrial, Irene M.; Chuma, Stacey; DeAngelo, Daniel; Treon, Steven P.] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Witzig, Thomas E.; Gertz, Morie; LaPlant, Betsy; Hayman, Suzanne; Camoriano, John; Lacy, Martha] Mayo Clin, Coll Med, Rochester, MN USA.
[Witzig, Thomas E.; Gertz, Morie; LaPlant, Betsy; Hayman, Suzanne; Camoriano, John; Lacy, Martha] Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA.
[Bergsagel, P. Leif] Mayo Clin, Coll Med, Scottsdale, AZ USA.
[Bergsagel, P. Leif] Mayo Fdn, Scottsdale, AZ USA.
RP Treon, SP (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.
EM steven_treon@dfci.harvard.edu
FU Novartis Inc, International Waldenstrom Macroglobulinemia Foundation
[1R01FD003743]
FX Contract grant sponsor: Novartis Inc, International Waldenstrom
Macroglobulinemia Foundation; Contract grant number: 1R01FD003743.
NR 48
TC 24
Z9 24
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0361-8609
EI 1096-8652
J9 AM J HEMATOL
JI Am. J. Hematol.
PD MAR
PY 2014
VL 89
IS 3
BP 237
EP 242
DI 10.1002/ajh.23620
PG 6
WC Hematology
SC Hematology
GA AB7AL
UT WOS:000331941600001
PM 24716234
ER
PT J
AU Castillo, JJ
Winer, ES
Olszewski, AJ
AF Castillo, Jorge J.
Winer, Eric S.
Olszewski, Adam J.
TI Sites of extranodal involvement are prognostic in patients with diffuse
large B-cell lymphoma in the rituximab era: An analysis of the
Surveillance, Epidemiology and End Results database
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID NON-HODGKINS-LYMPHOMA; PRIMARY BONE LYMPHOMA; CLINICOPATHOLOGICAL
FEATURES; RACIAL-DIFFERENCES; CLINICAL-FEATURES; WALDEYERS RING; PRIMARY
BREAST; ADULT PATIENTS; OUTCOMES; SURVIVAL
AB Approximately a third of the patients with diffuse large B-cell lymphoma present with extranodal involvement. Our study aims to identify primary extranodal sites of disease associated with prognosis in patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era. A secondary objective is to describe epidemiological and clinical characteristics of patients with extranodal DLBCL. We included adult patients from the Surveillance, Epidemiology and End Results (SEER) database (2004-2009) in whom DLBCL was the first malignancy diagnosed. Extranodal primary sites were divided into 12 groups according to the topography code reported by SEER. Multivariate overall survival (OS) analyses were performed using Cox proportional-hazard regression models adjusted for age, sex, race, and stage. From a total of 25,992 adult DLBCL patients included in our analysis, 32% presented with extranodal primary sites. Gastrointestinal tract (34%), head/neck (H & N; 14%), and skin/soft tissue (11%) were the most common. In comparison with nodal DLBCL, patients with extranodal involvement were older (with exception of skeletal sites) and presented with earlier stages. In the multivariate analysis, sites associated with worse OS rates were gastrointestinal (Hazard ratio (HR) 1.24, 95% confidence interval (CI) 1.15-1.33; P <0.001), pulmonary (HR 1.59, 95% CI 1.38-1.83; P <0.001), and liver/pancreas (HR 1.58, 95% CI 1.35-1.85; P <0.001), whereas H&N was associated with better survival (HR 0.79, 95% CI 0.70-0.89; P <0.001). In this population-based study, primary extranodal sites of involvement are associated with distinct outcomes in patients with DLBCL. Gastrointestinal, pulmonary, and liver/pancreas sites had a significant worse outcome than nodal sites. Am. J. Hematol. 89:310-314, 2014. (c) 2013 Wiley Periodicals, Inc.
C1 [Castillo, Jorge J.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA.
[Winer, Eric S.] Rhode Isl Hosp, Div Hematol & Oncol, Providence, RI USA.
[Winer, Eric S.] Miriam Hosp, Providence, RI 02906 USA.
[Olszewski, Adam J.] Brown Univ, Mem Hosp Rhode Isl, Div Hematol & Oncol, Pawtucket, RI 02860 USA.
RP Castillo, JJ (reprint author), 450 Brookline Ave,M221, Boston, MA 02215 USA.
EM jorgej_castillo@dfci.harvard.edu
OI Olszewski, Adam/0000-0002-6472-6658; Castillo, Jorge/0000-0001-9490-7532
NR 31
TC 16
Z9 17
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0361-8609
EI 1096-8652
J9 AM J HEMATOL
JI Am. J. Hematol.
PD MAR
PY 2014
VL 89
IS 3
BP 310
EP 314
DI 10.1002/ajh.23638
PG 5
WC Hematology
SC Hematology
GA AB7AL
UT WOS:000331941600013
PM 24273125
ER
PT J
AU Widemann, BC
Acosta, MT
Ammoun, S
Belzberg, AJ
Bernards, A
Blakeley, J
Bretscher, A
Cichowski, K
Clapp, DW
Dombi, E
Evans, GD
Ferner, R
Fernandez-Valle, C
Fisher, MJ
Giovannini, M
Gutmann, DH
Hanemann, CO
Hennigan, R
Huson, S
Ingram, D
Kissil, J
Korf, BR
Legius, E
Packer, RJ
McClatchey, AI
McCormick, F
North, K
Pehrsson, M
Plotkin, SR
Ramesh, V
Ratner, N
Schirmer, S
Sherman, L
Schorry, E
Stevenson, D
Stewart, DR
Ullrich, N
Bakker, AC
Morrison, H
AF Widemann, Brigitte C.
Acosta, Maria T.
Ammoun, Sylvia
Belzberg, Allan J.
Bernards, Andre
Blakeley, Jaishri
Bretscher, Antony
Cichowski, Karen
Clapp, D. Wade
Dombi, Eva
Evans, Gareth D.
Ferner, Rosalie
Fernandez-Valle, Cristina
Fisher, Michael J.
Giovannini, Marco
Gutmann, David H.
Hanemann, C. Oliver
Hennigan, Robert
Huson, Susan
Ingram, David
Kissil, Joe
Korf, Bruce R.
Legius, Eric
Packer, Roger J.
McClatchey, Andrea I.
McCormick, Frank
North, Kathryn
Pehrsson, Minja
Plotkin, Scott R.
Ramesh, Vijaya
Ratner, Nancy
Schirmer, Susann
Sherman, Larry
Schorry, Elizabeth
Stevenson, David
Stewart, Douglas R.
Ullrich, Nicole
Bakker, Annette C.
Morrison, Helen
TI CTF Meeting 2012: Translation of the Basic Understanding of the Biology
and Genetics of NF1, NF2, and Schwannomatosis Toward the Development of
Effective Therapies
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE neurofibromatosis type 1; neurofibromatosis type 2; NF1; NF2;
schwannomatosis; tumor suppressor; SMARCB1; merlin neurofibromin;
preclinical models
ID HISTONE DEACETYLASE INHIBITOR; NEUROFIBROMATOSIS TYPE-2; VESTIBULAR
SCHWANNOMAS; FAMILIAL SCHWANNOMATOSIS; SPORADIC SCHWANNOMATOSIS;
RETROSPECTIVE ANALYSIS; MULTIPLE MENINGIOMAS; DIAGNOSTIC-CRITERIA;
SMARCB1 MUTATIONS; CLINICAL ARTICLE
AB The neurofibromatoses (NF) are autosomal dominant genetic disorders that encompass the rare diseases NF1, NF2, and schwannomatosis. The NFs affect more people worldwide than Duchenne muscular dystrophy and Huntington's disease combined. NF1 and NF2 are caused by mutations of known tumor suppressor genes (NF1 and NF2, respectively). For schwannomatosis, although mutations in SMARCB1 were identified in a subpopulation of schwannomatosis patients, additional causative gene mutations are still to be discovered. Individuals with NF1 may demonstrate manifestations in multiple organ systems, including tumors of the nervous system, learning disabilities, and physical disfigurement. NF2 ultimately can cause deafness, cranial nerve deficits, and additional severe morbidities caused by tumors of the nervous system. Unmanageable pain is a key finding in patients with schwannomatosis. Although today there is no marketed treatment for NF-related tumors, a significant number of clinical trials have become available. In addition, significant preclinical efforts have led to a more rational selection of potential drug candidates for NF trials. An important element in fueling this progress is the sharing of knowledge. For over 20 years the Children's Tumor Foundation has convened an annual NF Conference, bringing together NF professionals to share novel findings, ideas, and build collaborations. The 2012 NF Conference held in New Orleans hosted over 350 NF researchers and clinicians. This article provides a synthesis of the highlights presented at the conference and as such, is a state-of-the-field for NF research in 2012. (c) 2014 Wiley Periodicals, Inc.
C1 [Widemann, Brigitte C.; Dombi, Eva] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Acosta, Maria T.; Packer, Roger J.] Gilbert NF Inst, Washington, DC USA.
[Ammoun, Sylvia; Hanemann, C. Oliver] Univ Plymouth, Peninsula Sch Med, Plymouth PL4 8AA, Devon, England.
[Ammoun, Sylvia; Hanemann, C. Oliver] Univ Plymouth, Peninsula Sch Dent, Plymouth PL4 8AA, Devon, England.
[Belzberg, Allan J.; Blakeley, Jaishri] Johns Hopkins Univ, Baltimore, MD USA.
[Bernards, Andre; McClatchey, Andrea I.; Plotkin, Scott R.; Ramesh, Vijaya] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA.
[Bernards, Andre; McClatchey, Andrea I.; Plotkin, Scott R.; Ramesh, Vijaya] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA.
[Bretscher, Antony] Cornell Univ, New York, NY 10021 USA.
[Cichowski, Karen] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Clapp, D. Wade; Ingram, David] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Evans, Gareth D.; Huson, Susan] Univ Manchester, St Marys Hosp, Manchester M13 0JH, Lancs, England.
[Ferner, Rosalie] Guys & St Thomas NHS Fdn Trust, London, England.
[Ferner, Rosalie] Kings Coll London, Dept Clin Neurosci, London, England.
[Fernandez-Valle, Cristina] Univ Cent Florida, Orlando, FL 32816 USA.
[Fisher, Michael J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Giovannini, Marco] Univ So Calif, House Res Inst, Los Angeles, CA USA.
[Gutmann, David H.] Washington Univ, Sch Med, St Louis, MO USA.
[Hennigan, Robert; Ratner, Nancy; Schorry, Elizabeth] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Kissil, Joe] Scripps Res Inst Florida, Jupiter, FL USA.
[Korf, Bruce R.] Univ Alabama Birmingham, Birmingham, AL USA.
[Legius, Eric] Catholic Univ Louvain, B-3000 Louvain, Belgium.
[McCormick, Frank] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[North, Kathryn] Childrens Hosp, Westmead, NSW, Australia.
[Pehrsson, Minja] Biomed Helsinki, Helsinki, Finland.
[Schirmer, Susann; Morrison, Helen] Leibniz Inst Age Res, Jena, Germany.
[Sherman, Larry] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Stevenson, David] Univ Utah, Salt Lake City, UT USA.
[Stewart, Douglas R.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Ullrich, Nicole] Childrens Hosp, Boston, MA 02115 USA.
[Bakker, Annette C.] Childrens Tumor Fdn, New York, NY 10005 USA.
RP Bakker, AC (reprint author), Childrens Tumor Fdn, 95 Pine St, New York, NY 10005 USA.
EM widemanb@mail.nih.gov; abakker@ctf.org
RI North, Kathryn/K-6476-2012; Morrison, Helen/B-3984-2017;
OI North, Kathryn/0000-0003-0841-8009; Morrison, Helen/0000-0003-4938-1409;
Hanemann, Clemens Oliver/0000-0002-1951-1025; Evans,
Gareth/0000-0002-8482-5784
FU National Institutes of Health Grant Award [1R13NS070505-01]; Center for
Cancer Research; National Cancer Institute
FX Grant sponsor: National Institutes of Health Grant Award; Grant number:
1R13NS070505-01; Grant sponsor: Center for Cancer Research; Grant
sponsor: National Cancer Institute.
NR 70
TC 4
Z9 4
U1 0
U2 15
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 MAR
PY 2014
VL 164
IS 3
BP 563
EP 578
DI 10.1002/ajmg.a.36312
PG 16
WC Genetics & Heredity
SC Genetics & Heredity
GA AB7NZ
UT WOS:000331978700001
PM 24443315
ER
PT J
AU Ting, CK
Johnson, KB
Teng, WN
Synoid, ND
LaPierre, C
Yu, L
Westenskow, DR
AF Ting, Chien-Kun
Johnson, Ken B.
Teng, Wei-Nung
Synoid, Noah D.
LaPierre, Cris
Yu, Lu
Westenskow, Dwayne R.
TI Response Surface Model Predictions of Wake- Up Time During Scoliosis
Surgery
SO ANESTHESIA AND ANALGESIA
LA English
DT Article
ID ALVEOLAR ANESTHETIC CONCENTRATION; PROPOFOL-REMIFENTANIL ANESTHESIA;
SEVOFLURANE REQUIREMENTS; UP TEST; INHALATION ANESTHESIA;
CONCENTRATION-AWAKE; CONTROLLED INFUSION; SYSTEM MODEL; FENTANYL;
DESFLURANE
AB BACKGROUND: With the use of previously published data, new sevoflurane-remifentanil interaction models of various degrees of sedation were created and adapted to desflurane-fentanyl by using minimal alveolar concentration and opioid equivalencies. These models were used to predict return of responsiveness in patients undergoing scoliosis surgery during a wake-up test. Our hypothesis was that one of the interaction models would accurately predict return of responsiveness during a wake-up test.
METHODS: Three new sevoflurane-remifentanil interaction models were constructed from previous observations in volunteers by using the Observer's Assessment of Alertness/Sedation (OAA/S) scores. These models included predictions of OAA/S<2 (unresponsive), OAA/S< 3, and OAA/S<4 (sedation). Twenty-three patients scheduled for scoliosis surgery received a fentanyl-desflurane anesthetic. With the use of published pharmacokinetic models, predictions of fentanyl and desflurane effect-site concentrations were recorded throughout surgery and converted to equivalent remifentanil and sevoflurane effect-site concentrations. Data were recorded every 10 seconds from the time when desflurane was turned off until 10 minutes after the patients responded by moving their hands and toes. Model predictions were compared with observations with graphical and temporal analyses.
RESULTS: The average difference between the time when a patient first responded and the time when the model predicted that there was a 50% probability that the patient would respond were -2.6 3.6 minutes (mean +/- SD) for the OAA/S<2 model, 2.8 +/- 5.6 minutes for the OAA/S<3 model and 52.6 +/- 32.3 minutes for the OAA/S<4 model.
CONCLUSIONS: The results confirmed our study hypothesis; a sevoflurane-remifentanil interaction model built from observations in volunteers and adapted to desflurane and fentanyl accurately predicted patient response during a wake-up test. These results were similar to our previous study comparing model predictions and patient observations after a sevoflurane-remifentanil/fentanyl anesthetic. The OAA/S <2 model most accurately predicted the time patients would respond by moving their fingers and toes. This model may help anesthesiologists better predict return of responsiveness during a wake-up test in patients undergoing spine surgery.
C1 [Ting, Chien-Kun; Teng, Wei-Nung] Taipei Vet Gen Hosp, Dept Anesthesiol, Taipei, Taiwan.
[Ting, Chien-Kun; Teng, Wei-Nung] Natl Yang Ming Univ, Taipei 112, Taiwan.
[Johnson, Ken B.; Synoid, Noah D.; Westenskow, Dwayne R.] Univ Utah Sch Med, Dept Anesthesiol, Salt Lake City, UT USA.
[Johnson, Ken B.; Westenskow, Dwayne R.] Univ Utah, Dept Bioengn, Salt Lake City, UT 84112 USA.
[LaPierre, Cris] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
[LaPierre, Cris] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Yu, Lu] China Med Univ, Dept Biomed Engn, Coll Basic Med Sci, Shenyang, Liaoning, Peoples R China.
RP Ting, CK (reprint author), Taipei Vet Gen Hosp, Dept Anesthesiol, 201,Sect 2,Shi Pai Rd, Taipei, Taiwan.
EM ckting2@gmail.com
RI Ting, Chien-Kun/C-1389-2012
OI Ting, Chien-Kun/0000-0002-3156-8139
NR 41
TC 6
Z9 6
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-2999
EI 1526-7598
J9 ANESTH ANALG
JI Anesth. Analg.
PD MAR
PY 2014
VL 118
IS 3
BP 546
EP 553
DI 10.1213/ANE.0000000000000094
PG 8
WC Anesthesiology
SC Anesthesiology
GA AG4NG
UT WOS:000335396200012
PM 24557102
ER
PT J
AU Ge, R
Pejo, E
Gallin, H
Jeffrey, S
Cotten, JF
Raines, DE
AF Ge, Rile
Pejo, Ervin
Gallin, Hilary
Jeffrey, Spencer
Cotten, Joseph F.
Raines, Douglas E.
TI The Pharmacology of Cyclopropyl-Methoxycarbonyl Metomidate: A Comparison
with Propofol
SO ANESTHESIA AND ANALGESIA
LA English
DT Article
ID MULTIPLE TRAUMA PATIENTS; ADRENOCORTICAL SUPPRESSION; ETOMIDATE ANALOG;
PROTEIN-BINDING; IN-VIVO; ANESTHESIA; MAINTENANCE; INHIBITION;
METABOLITE; INFUSIONS
AB BACKGROUND: Cyclopropyl-methoxycarbonyl metomidate (CPMM) is a soft etomidate analogue currently being developed as a propofol alternative for anesthetic induction and maintenance.
METHODS: We compared the potencies of CPMM and propofol by assessing their abilities to directly activate (1)(L264T)(32) gamma-aminobutyric acid type A (GABA(A)) receptors and induce loss of righting reflexes in tadpoles. We also measured the rates of encephalographic recovery in rats after CPMM and propofol infusions ranging in duration from 5 to 120 minutes.
RESULTS: CPMM and propofol activate GABA(A) receptors and induce loss of righting reflexes in tadpoles with respective 50% effective concentrations (EC50s) of 3.8 0.4 and 3.9 +/- 0.2 M (GABA(A) receptor) and 2.6 +/- 0.19 and 1.3 +/- 0.04 M (tadpole). Encephalographic recovery after prolonged infusion was faster with CPMM and lacked propofol's context sensitivity.
CONCLUSION: CPMM and propofol have similar potencies in GABA(A) receptors and tadpoles; however, CPMM provides more rapid and predictable recovery than propofol, particularly after prolonged infusion.
C1 [Ge, Rile] Boston Childrens Hosp, Dept Anesthesia Perioperat & Pain Med, Boston, MA USA.
[Pejo, Ervin; Jeffrey, Spencer; Cotten, Joseph F.; Raines, Douglas E.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Gallin, Hilary] Washington Univ Sch Med, St Louis, MO USA.
RP Raines, DE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA.
EM draines@partners.org
FU National Institutes of Health, Bethesda, MD [R01-GM087316]; Department
of Anesthesia, Critical Care & Pain Medicine at the Massachusetts
General Hospital; [K08-GM083216]
FX This research was supported by grants to DER (R01-GM087316 from the
National Institutes of Health, Bethesda, MD) and JFC (K08-GM083216), and
by the Department of Anesthesia, Critical Care & Pain Medicine at the
Massachusetts General Hospital.
NR 19
TC 8
Z9 8
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0003-2999
J9 ANESTH ANALG
JI Anesth. Analg.
PD MAR
PY 2014
VL 118
IS 3
BP 563
EP 567
DI 10.1213/ANE.0000000000000069
PG 5
WC Anesthesiology
SC Anesthesiology
GA AG4NG
UT WOS:000335396200014
PM 24557104
ER
PT J
AU El-Orbany, M
Ali, HH
Baraka, A
Salem, MR
AF El-Orbany, Mohammad
Ali, Hassan H.
Baraka, Anis
Salem, M. Ramez
TI Residual Neuromuscular Block Should, and Can, Be a "Never Event"
SO ANESTHESIA AND ANALGESIA
LA English
DT Letter
ID CLINICAL RECOVERY
C1 [El-Orbany, Mohammad] Med Coll Wisconsin, Dept Anesthesiol, Milwaukee, WI 53226 USA.
[Ali, Hassan H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA USA.
[Baraka, Anis] Amer Univ Beirut, Dept Anesthesiol, Beirut, Lebanon.
[Salem, M. Ramez] Advocate Illinois Masonic Med Ctr, Dept Anesthesiol, Chicago, IL USA.
RP El-Orbany, M (reprint author), Med Coll Wisconsin, Dept Anesthesiol, Milwaukee, WI 53226 USA.
EM elorbany@mcw.edu
NR 9
TC 3
Z9 3
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-2999
EI 1526-7598
J9 ANESTH ANALG
JI Anesth. Analg.
PD MAR
PY 2014
VL 118
IS 3
BP 691
EP 691
DI 10.1213/ANE.0000000000000090
PG 1
WC Anesthesiology
SC Anesthesiology
GA AG4NG
UT WOS:000335396200035
PM 24557116
ER
PT J
AU Arriaga, AF
Gawande, AA
Raemer, DB
Jones, DB
Smink, DS
Weinstock, P
Dwyer, K
Lipsitz, SR
Peyre, S
Pawlowski, JB
Muret-Wagstaff, S
Gee, D
Gordon, JA
Cooper, JB
Berry, WR
AF Arriaga, Alexander F.
Gawande, Atul A.
Raemer, Daniel B.
Jones, Daniel B.
Smink, Douglas S.
Weinstock, Peter
Dwyer, Kathy
Lipsitz, Stuart R.
Peyre, Sarah
Pawlowski, John B.
Muret-Wagstaff, Sharon
Gee, Denise
Gordon, James A.
Cooper, Jeffrey B.
Berry, William R.
CA Harvard Surg Safety Collaborative
TI Pilot Testing of a Model for Insurer-Driven, Large-Scale Multicenter
Simulation Training for Operating Room Teams
SO ANNALS OF SURGERY
LA English
DT Article
DE medical simulation; operating room teamwork training; patient safety
ID CRISIS RESOURCE-MANAGEMENT; SURGICAL SAFETY CHECKLIST; 2000 INCIDENT
REPORTS; CLINICAL-PERFORMANCE; NONTECHNICAL SKILLS; TEACHING HOSPITALS;
MALPRACTICE CLAIMS; ANESTHETIC CRISIS; CARDIAC-SURGERY; PATIENT SAFETY
AB Objective: To test the feasibility of implementing a standardized teamwork training program with full operating room teams in multiple institutions, driven by malpractice insurer support and incentives.
Background: Failures in intraoperative teamwork are among the leading causes of preventable patient injury and death in surgical patients. Teamwork training, particularly using simulation, can be an effective intervention but is difficult to scale.
Methods: A malpractice insurer convened a collaborative with 4 Harvard-affiliated simulation programs to develop a standardized operating room teamwork training curriculum, including principles of communication, assertiveness, and use of the World Health Organization Surgical Safety Checklist. Participant teams were compensated for lost operative time via malpractice premium discounts, continuing education credits, and compensation for lost wages. The course was delivered through a simulation program involving the management of intraoperative emergency scenarios. Participants were surveyed for their perceptions of the program and of its impact on clinical practice.
Results: A total of 221 active operating room staff members participated in the program. Each team contained at least 1 attending surgeon, 1 attending anesthesiologist, and 1 operating room nurse (mean size per team: 7 2 participants). No study dates were cancelled because of lack of attendance. The survey response rate was 99% (218/221). Overall, the vast majority of participants found the scenarios realistic [94% (95% confidence interval: 90.9%, 97.2%)], appropriately challenging [95.4% (92.6%, 98.2%)], relevant to their practice [96.3% (93.8%, 98.8%)], and found the training would help them provide safer patient care [92.6% (89.1%, 96.1%)]. Surgeons reported their greatest personal deficit as communication skills. Operating room nurses and anesthesiologists reported a greater need than surgeons to work on personal assertiveness.
Conclusions: A standardized multicenter team training program involving full operative teams is feasible with high-fidelity simulation and modest compensation for lost time. The vast majority of the multidisciplinary participants believed the course to have had a meaningful impact on their approach to clinical practice.
C1 [Arriaga, Alexander F.; Gawande, Atul A.; Smink, Douglas S.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
[Arriaga, Alexander F.] Brigham & Womens Hosp, Dept Anesthesiol Pain & Perioperat Med, Boston, MA 02115 USA.
[Arriaga, Alexander F.; Gawande, Atul A.; Berry, William R.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
[Arriaga, Alexander F.; Gawande, Atul A.; Lipsitz, Stuart R.; Berry, William R.] Ariadne Labs, Boston, MA USA.
[Arriaga, Alexander F.; Gawande, Atul A.; Smink, Douglas S.; Lipsitz, Stuart R.; Berry, William R.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA.
[Raemer, Daniel B.; Cooper, Jeffrey B.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Raemer, Daniel B.; Gee, Denise; Cooper, Jeffrey B.] Ctr Med Simulat, Cambridge, MA USA.
[Jones, Daniel B.] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA.
[Jones, Daniel B.; Pawlowski, John B.; Muret-Wagstaff, Sharon] Beth Israel Deaconess Med Ctr, Carl J Shapiro Simulat & Skills Ctr, Boston, MA 02215 USA.
[Smink, Douglas S.] Brigham & Womens Hosp, STRATUS Ctr Med Simulat, Boston, MA 02115 USA.
[Weinstock, Peter] Boston Childrens Hosp, Dept Anesthesia, Div Crit Care Med, Boston, MA USA.
[Weinstock, Peter] Boston Childrens Hosp, Simulator Program, Boston, MA USA.
[Dwyer, Kathy] Harvard Med Inst CRICO RMF, Risk Management Fdn, Cambridge, MA USA.
[Lipsitz, Stuart R.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Peyre, Sarah] Univ Rochester, Dept Surg, Rochester, NY USA.
[Pawlowski, John B.; Muret-Wagstaff, Sharon] Beth Israel Deaconess Med Ctr, Dept Anesthesia & Crit Care, Boston, MA 02215 USA.
[Gee, Denise] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Gordon, James A.] Harvard Univ, Sch Med, Gilbert Program Med Simulat, Boston, MA USA.
[Gordon, James A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
RP Arriaga, AF (reprint author), Harvard Univ, Sch Publ Hlth, 677 Huntington Ave, Boston, MA 02115 USA.
EM wberry@hsph.harvard.edu
FU Risk Management Foundation of the Harvard Medical Institutions
(CRICO/RMF); United States Army Medical Research Acquisition
[W81XWH-09-2-001]
FX This study was supported by a grant from the Risk Management Foundation
of the Harvard Medical Institutions (CRICO/RMF). Kathy Dwyer is a senior
program director and William R. Berry is the associate medical director
for CRICO/RMF. Jeffrey B. Cooper is the executive director for the
Center for Medical Simulation, a nonprofit research and education
organization that provides fee for service programs of the type
described in this report. James A. Gordon is supported by contract
W81XWH-09-2-001 under a cooperative agreement issued by the United
States Army Medical Research Acquisition. No other disclosures relevant
to the work were made by the remaining authors.
NR 85
TC 24
Z9 24
U1 6
U2 18
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-4932
EI 1528-1140
J9 ANN SURG
JI Ann. Surg.
PD MAR
PY 2014
VL 259
IS 3
BP 403
EP 410
DI 10.1097/SLA.0000000000000342
PG 8
WC Surgery
SC Surgery
GA AH6NQ
UT WOS:000336248000018
PM 24263327
ER
PT J
AU Fernandez-del Castillo, CF
Thayer, SP
Ferrone, CR
Wargo, J
AF Fernandez-del Castillo, Carlos F.
Thayer, Sarah P.
Ferrone, Cristina R.
Wargo, Jennifer
TI Surgery for Small and Asymptomatic Branch-Duct IPMNs
SO ANNALS OF SURGERY
LA English
DT Letter
ID NEOPLASMS
C1 [Fernandez-del Castillo, Carlos F.; Thayer, Sarah P.; Ferrone, Cristina R.; Wargo, Jennifer] Massachusetts Gen Hosp, Pancreas & Biliary Surg Program, Boston, MA 02114 USA.
RP Fernandez-del Castillo, CF (reprint author), Massachusetts Gen Hosp, Pancreas & Biliary Surg Program, Boston, MA 02114 USA.
EM cfernandez@partners.org
NR 4
TC 7
Z9 7
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-4932
EI 1528-1140
J9 ANN SURG
JI Ann. Surg.
PD MAR
PY 2014
VL 259
IS 3
BP E47
EP E47
DI 10.1097/SLA.0000000000000270
PG 1
WC Surgery
SC Surgery
GA AH6NQ
UT WOS:000336248000008
PM 24096750
ER
PT J
AU Carillo, S
Zhang, Y
Fay, R
Angioi, M
Vincent, J
Sutradhor, SC
Ahmed, A
Pitt, B
Zannad, F
AF Carillo, Sylvain
Zhang, Yan
Fay, Renaud
Angioi, Michael
Vincent, John
Sutradhor, Santosh C.
Ahmed, Ali
Pitt, Bertram
Zannad, Faiez
TI Heart failure with systolic dysfunction complicating acute myocardial
infarction - differential outcomes but similar eplerenone efficacy by
ST-segment or non-ST-segment elevation: A post hoc substudy of the
EPHESUS trial
SO ARCHIVES OF CARDIOVASCULAR DISEASES
LA English
DT Article
DE NSTEMI; STEMI; Heart failure; Eplerenone
ID ACUTE CORONARY SYNDROMES; PRACTICE GUIDELINES COMMITTEE;
LEFT-VENTRICULAR DYSFUNCTION; ASSOCIATION TASK-FORCE; MEDITERRANEAN
BASIN; ACC/AHA GUIDELINES; HOSPITAL MORTALITY; NATIONAL REGISTRY;
AMERICAN-COLLEGE; UNSTABLE ANGINA
AB Background. - Differential outcomes in patients with acute systolic heart failure (HF) complicating acute myocardial infarction (AMI) and the efficacy of mineralocorticoid receptor antagonists according to non-ST-segment and ST-segment elevation myocardial infarction (NSTEMI, STEM!) status has not been specifically investigated.
Methods. - In the EPHESUS study, 6632 patients with acute HF and left ventricular ejection fraction <40% were randomized 3-14 days post-AMI (median 7.3+/-3.0 days) to receive eplerenone (n=3319) or placebo (n=3313). Among them, 6392 patients with available data on baseline ST-segment status (4634 STEMI; 1758 NSTEMI) were compared using a Cox model analysis stratified according to quintiles of propensity score (PS), taking into account major baseline risk factors, including revascularization.
Results. - STEMI and NSTEMI patients differed significantly across a large variety of baseline characteristics. During 30 months of follow-up, all-cause death occurred in 19% and 13% (P<0.0001), cardiovascular death in 16% and 12% (P<0.0001), cardiovascular death and hospitalization in 33% and 26% (P<0.0001) and death from progression of HF in 5% and 3% (P<0.0001) of unadjusted NSTEMI and STEMI patients, respectively. After Cox model PS adjustment without revascularization, NSTEMI status still proved to be a risk factor for all-cause death, cardiovascular death and death from progression of HE After Cox model PS adjustment including revascularization, none of the outcomes differed between STEMI and NSTEMI patients. Eplerenone morbidity and mortality benefits were consistent in the STEMI and NSTEMI subgroups.
Conclusion. - In patients with acute systolic HF complicating AMI, eplerenone improves outcomes equally in STEMI and NSTEMI patients. Worse outcomes associated with NSTEMI could be explained by more co-morbidities, less aggressive therapies and, mainly, less frequent revascularization. (C) 2014 Elsevier Masson SAS. All rights reserved.
C1 [Carillo, Sylvain; Fay, Renaud; Zannad, Faiez] CHU Nancy, CIC9501, Inst Lorrain Coeur & Vaisseaux, Inserm U961, F-54500 Vandoeuvre Les Nancy, France.
[Zhang, Yan; Ahmed, Ali] Univ Alabama Birmingham, Birmingham & VA Med Ctr, Birmingham, AL USA.
[Angioi, Michael] Clin Louis Pasteur, F-54270 Esseys Les Nancy, France.
[Vincent, John; Sutradhor, Santosh C.] Pfizer Inc, New York, NY USA.
[Pitt, Bertram] Univ Michigan, Ann Arbor, MI 48109 USA.
RP Carillo, S (reprint author), CHU Nancy, CIC9501, Inst Lorrain Coeur & Vaisseaux, Inserm U961, 2 Ave Morvan, F-54500 Vandoeuvre Les Nancy, France.
EM s.carillo@chu-nancy.fr
FU Novartis; Medtronic; Forrest Laboratories; BG Medicine; Roche
Diagnostics
FX Sylvain Carillo, Renaud Fay and Mickael Angioi: none. Yan Zhang:
affiliation with UAB. John Vincent and Santosh C. Sutradhor: Pfizer Inc.
employees. Ali Ahmed: affiliation with UAB and VA. Bertram Pitt:
consultant for Pfizer, Merck, Novartis, Bayer, Takeda, AstraZeneca,
Lilly, BMS, BG Medicine (stock options), Relypsa (stock options),
Cytopherx, Amorcyte, Aurasence (stock options) and Ardelyx; grants from
Novartis, Medtronic and Forrest Laboratories. Faiez Zannad: grants to
institution from BG Medicine and Roche Diagnostics; consultant/member of
steering committees, event committees and data safety monitoring boards
for Bayer, Biomerieux, Biotronik, Boston Scientific, CVCT, Novartis,
Pfizer, Resmed, Servier and Takeda.
NR 38
TC 1
Z9 1
U1 1
U2 1
PU ELSEVIER MASSON
PI MILANO
PA VIA PALEOCAPA 7, 20121 MILANO, ITALY
SN 1875-2136
EI 1875-2128
J9 ARCH CARDIOVASC DIS
JI Arch. Cardiovasc. Dis.
PD MAR
PY 2014
VL 107
IS 3
BP 149
EP 157
DI 10.1016/j.acvd.2014.01.010
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AH7XA
UT WOS:000336347500002
PM 24630753
ER
PT J
AU Hegde, M
Lowenstein, DH
AF Hegde, Manu
Lowenstein, Daniel H.
TI The search for circulating epilepsy biomarkers
SO BIOMARKERS IN MEDICINE
LA English
DT Article
DE autoantibodies; biomarkers; blood; cerebrospinal fluid; epilepsy center
dot epileptogenesis; inflammation; pharmacoresistance
ID TEMPORAL-LOBE EPILEPSY; PYRIDOXINE-DEPENDENT EPILEPSY; NMDA RECEPTOR
ENCEPHALITIS; STEVENS-JOHNSON-SYNDROME; ALPHA-AMINOADIPIC SEMIALDEHYDE;
GLUTAMIC-ACID DECARBOXYLASE; TUBEROUS SCLEROSIS COMPLEX; IMMATURE RAT
MODEL; DYSPLASIA TYPE IIB; STATUS EPILEPTICUS
AB Few would experience greater benefit from the development of biomarkers than those who suffer from epilepsy. Both the timing of individual seizures and the overall course of the disease are highly unpredictable, and the associated morbidity is considerable. Thus, there is an urgent need to develop biomarkers that can predict the progression of epilepsy and treatment response. Doing so may also shed light on the mechanisms of epileptogenesis and pharmacoresistance, which remain elusive despite decades of study. However, recent advances suggest the possible identification of circulating epilepsy biomarkers - accessible in blood, cerebrospinal fluid or urine. In this review, we focus on advances in several areas: neuroimmunology and inflammation; neurological viral infection; exemplary pediatric syndromes; and the genetics of pharmacoresistance, as relevant to epilepsy. These are fertile areas of study with great potential to yield accessible epilepsy biomarkers.
C1 [Hegde, Manu; Lowenstein, Daniel H.] Univ Calif San Francisco, Dept Neurol, UCSF Epilepsy Ctr, San Francisco, CA 94143 USA.
[Hegde, Manu] San Francisco VA Med Ctr, Epilepsy Ctr Excellence, San Francisco, CA 94121 USA.
RP Hegde, M (reprint author), Univ Calif San Francisco, Dept Neurol, UCSF Epilepsy Ctr, 521 Parnassus Ave C-440, San Francisco, CA 94143 USA.
EM manu.hegde@ucsf.edu
NR 99
TC 10
Z9 11
U1 0
U2 8
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1752-0363
EI 1752-0371
J9 BIOMARK MED
JI Biomark. Med.
PD MAR
PY 2014
VL 8
IS 3
BP 413
EP 427
DI 10.2217/BMM.13.142
PG 15
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AE4RN
UT WOS:000333970700018
PM 24712433
ER
PT J
AU Qian, J
Payabvash, S
Kemmling, A
Lev, MH
Schwamm, LH
Betensky, RA
AF Qian, Jing
Payabvash, Seyedmehdi
Kemmling, Andre
Lev, Michael H.
Schwamm, Lee H.
Betensky, Rebecca A.
TI Variable Selection and Prediction Using a Nested, Matched Case-Control
Study: Application to Hospital Acquired Pneumonia in Stroke Patients
SO BIOMETRICS
LA English
DT Article
DE AUC; Cerebral infarction; Conditional logistic regression; Elastic net;
Lasso; Penalized likelihood; ROC analysis
ID GENOME-WIDE ASSOCIATION; LOGISTIC-REGRESSION; LASSO; CLASSIFICATION; MRI
AB Matched case-control designs are commonly used in epidemiologic studies for increased efficiency. These designs have recently been introduced to the setting of modern imaging and genomic studies, which are characterized by high-dimensional covariates. However, appropriate statistical analyses that adjust for the matching have not been widely adopted. A matched case-control study of 430 acute ischemic stroke patients was conducted at Massachusetts General Hospital (MGH) in order to identify specific brain regions of acute infarction that are associated with hospital acquired pneumonia (HAP) in these patients. There are 138 brain regions in which infarction was measured, which introduce nearly 10,000 two-way interactions, and challenge the statistical analysis. We investigate penalized conditional and unconditional logistic regression approaches to this variable selection problem that properly differentiate between selection of main effects and of interactions, and that acknowledge the matching. This neuroimaging study was nested within a larger prospective study of HAP in 1915 stroke patients at MGH, which recorded clinical variables, but did not include neuroimaging. We demonstrate how the larger study, in conjunction with the nested, matched study, affords us the capability to derive a score for prediction of HAP in future stroke patients based on imaging and clinical features. We evaluate the proposed methods in simulation studies and we apply them to the MGH HAP study.
C1 [Qian, Jing] Univ Massachusetts, Dept Biostat & Epidemiol, Amherst, MA 01003 USA.
[Qian, Jing; Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Payabvash, Seyedmehdi; Kemmling, Andre; Lev, Michael H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Qian, J (reprint author), Univ Massachusetts, Dept Biostat & Epidemiol, Amherst, MA 01003 USA.
EM qian@schoolph.umass.edu
OI Schwamm, Lee/0000-0003-0592-9145
FU Harvard NeuroDiscovery Center; Harvard Catalyst [8UL1TR000170]; NIH
[R01-CA075971]
FX The authors are grateful to the editor, the associate editor, and two
anonymous referees for their valuable comments. This research was
supported in part by the Harvard NeuroDiscovery Center, the Harvard
Catalyst (8UL1TR000170), NIH grant R01-CA075971.
NR 25
TC 4
Z9 5
U1 2
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0006-341X
EI 1541-0420
J9 BIOMETRICS
JI Biometrics
PD MAR
PY 2014
VL 70
IS 1
BP 153
EP 163
DI 10.1111/biom.12113
PG 11
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA AC4BS
UT WOS:000332466200003
PM 24320930
ER
PT J
AU Fadlallah, A
Atallah, M
Cherfan, G
Awwad, ST
Syed, ZA
Melki, SA
AF Fadlallah, Ali
Atallah, Marwan
Cherfan, George
Awwad, Shady T.
Syed, Zeba A.
Melki, Samir A.
TI Gamma-Irradiated Corneas as Carriers for the Boston Type 1
Keratoprosthesis: Advantages and Outcomes in a Surgical Mission Setting
SO CORNEA
LA English
DT Article
DE keratoprosthesis; gamma-irradiation; Beirut
ID SURGERY
AB Purpose:The Boston keratoprosthesis (KPro) is the most commonly used KPro worldwide. There are limited data on the outcomes when irradiated corneas are used as KPro carriers. We report a retrospective analysis of corneal transplantations performed in a regular surgical mission setting in Beirut, Lebanon, using the Boston KPro type 1 and gamma-irradiated carrier corneas, and we describe visual outcomes, complications, and retention percentage.Methods:We conducted a retrospective analysis of 17 consecutive eyes from 16 patients who underwent Boston KPro type 1 implantation at the Beirut Eye Specialist Hospital between December 2010 and July 2012. Patient medical records were reviewed for preoperative, intraoperative, and postoperative details.Results:Postoperatively, 9 (52.9%), 5 (29.4%), and 2 (11.7%) eyes had a corrected visual acuity of 20/400 or better, 20/100 or better, and 20/40 or better, respectively, at the most recent follow-up visit. A total of 16 eyes (94.1%) improved in corrected visual acuity over the course of follow-up. Overall, 13 eyes (76.4%) developed at least 1 complication after surgery. Retroprosthetic membrane formation was the most common complication, occurring in 10 eyes (58.8%). Neither infectious keratitis nor corneal stromal necrosis was noted during the follow-up period. The retention percentage was 94.1%.Conclusions:The visual acuity outcomes, incidence of complications, and retention percentage of the KPro using gamma-irradiated carrier corneas are comparable with the outcomes of KPro implantation reported in the literature using fresh grafts as carriers. KPro with irradiated corneal carrier grafts seems to be an effective option to increase the supply of transplantation suitable corneas in remote areas, where fresh corneal grafts may be scarce.
C1 [Fadlallah, Ali; Cherfan, George; Melki, Samir A.] Beirut Eye Specialist Hosp, Beirut, Lebanon.
[Fadlallah, Ali; Atallah, Marwan] St Joseph Univ, Fac Med, Beirut, Lebanon.
[Fadlallah, Ali; Atallah, Marwan] Univ Paris 04, UPMC, Paris, France.
[Awwad, Shady T.] Amer Univ Beirut, Med Ctr, Opthalmol Dept, Beirut, Lebanon.
[Syed, Zeba A.; Melki, Samir A.] Harvard Univ, Sch Med, Boston, MA USA.
[Melki, Samir A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA.
RP Melki, SA (reprint author), Massachusetts Eye & Ear Infirm, Cornea & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA.
EM samir_melki@meei.harvard.edu
NR 13
TC 2
Z9 2
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0277-3740
EI 1536-4798
J9 CORNEA
JI Cornea
PD MAR
PY 2014
VL 33
IS 3
BP 235
EP 239
DI 10.1097/ICO.0000000000000065
PG 5
WC Ophthalmology
SC Ophthalmology
GA AB1DD
UT WOS:000331530700004
PM 24457451
ER
PT J
AU Fava, M
Ball, S
Nelson, JC
Sparks, J
Konechnik, T
Classi, P
Dube, S
Thase, ME
AF Fava, Maurizio
Ball, Susan
Nelson, J. Craig
Sparks, JonDavid
Konechnik, Thomas
Classi, Peter
Dube, Sanjay
Thase, Michael E.
TI CLINICAL RELEVANCE OF FATIGUE AS A RESIDUAL SYMPTOM IN MAJOR DEPRESSIVE
DISORDER
SO DEPRESSION AND ANXIETY
LA English
DT Review
DE residual symptoms; fatigue; major depressive disorder; functioning;
remission
ID SEROTONIN REUPTAKE INHIBITORS; STAR-ASTERISK-D; SELECTIVE SEROTONIN;
DOUBLE-BLIND; CATECHOLAMINE DEPLETION; ANTIDEPRESSANT ACTION; PARTIAL
RESPONDERS; PHYSICAL SYMPTOMS; PARTIAL REMISSION; SLEEPINESS
AB Residual symptoms of major depressive disorder (MDD) following treatment are increasingly recognized as having a negative impact on the patient because of their association with lack of remission, poorer psychosocial functioning, and a more chronic course of depression. Although the effects of specific residual symptoms have not been as systematically studied, several symptoms, including fatigue, sleep disturbance, anxiety, and concentration difficulties, commonly occur as part of the residual state in MDD. In particular, the relatively high prevalence of residual fatigue suggests that this symptom is not being adequately addressed by standard antidepressant therapies. A review of the clinical relevance of residual fatigue was undertaken, using the published literature with respect to its assessment, neurobiology, and treatment implications. The findings of this review suggest that fatigue is highly prevalent as a residual symptom; its response to treatment is relatively poor or delayed; and the presence of residual fatigue is highly predictive of inability to achieve remission with treatment as well as impaired psychosocial functioning. Recognition of the significant consequences of residual fatigue should reinforce the need for further therapeutic interventions to help reduce the impact of this symptom of MDD.
C1 [Fava, Maurizio] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Ball, Susan; Sparks, JonDavid; Konechnik, Thomas; Classi, Peter] Lilly Res Labs, Indianapolis, IN USA.
[Ball, Susan; Dube, Sanjay] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA.
[Nelson, J. Craig] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Dube, Sanjay] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15260 USA.
[Thase, Michael E.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP Fava, M (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, 55 Fruit St,Bulfinch 351, Boston, MA 02114 USA.
EM mfava@partners.org
NR 61
TC 24
Z9 24
U1 0
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1091-4269
EI 1520-6394
J9 DEPRESS ANXIETY
JI Depress. Anxiety
PD MAR
PY 2014
VL 31
IS 3
BP 250
EP 257
DI 10.1002/da.22199
PG 8
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA AC3AE
UT WOS:000332386600009
PM 24115209
ER
PT J
AU Mueller, B
Ahnert, P
Burkhardt, J
Brauer, J
Czepezauer, I
Quente, E
Boltze, J
Wilcke, A
Kirsten, H
AF Mueller, B.
Ahnert, P.
Burkhardt, J.
Brauer, J.
Czepezauer, I.
Quente, E.
Boltze, J.
Wilcke, A.
Kirsten, H.
TI Genetic risk variants for dyslexia on chromosome 18 in a German cohort
SO GENES BRAIN AND BEHAVIOR
LA English
DT Article
DE Chromosome 18; dyslexia; genetic association studies; genetic
predisposition to disease; German primary school students; linkage
disequilibrium; quantitative association study; replication study;
single nucleotide polymorphism
ID DEVELOPMENTAL DYSLEXIA; LINKAGE ANALYSES; GENOMEWIDE SCAN;
BLOOD-PRESSURE; LOCUS; ASSOCIATION; DISABILITIES; SAMPLE; TRAIT
AB Dyslexia is characterized by impaired reading and spelling. The disorder has a prevalence of about 5% in Germany, and a strong hereditary component. Several loci are thought to be involved in the development of dyslexia. Scerri et al. identified eight potential dyslexia-associated single nucleotide polymorphisms (SNPs) in seven genes on chromosome 18 in an English-speaking population. Here, we present an association analysis that explores the relevance of these SNPs in a German population comprising 388 dyslexia cases and 364 control cases. In case-control analysis, three nominal SNP associations were replicated. The major alleles of NEDD4L-rs12606138 and NEDD4L-rs8094327 were risk associated [odds ratio (OR)=1.35, 95% confidence interval (CI)=1.0-1.7, P-value=0.017 and OR=1.39, 95% CI=1.1-1.7, P-value=0.007, respectively], and both SNPs were in strong linkage disequilibrium (r(2)=0.95). For MYO5B-rs555879, the minor allele was risk associated (OR=1.31, 95% CI=1.1-1.6, P-value=0.011). The combined analysis of SNP sets using set enrichment analysis revealed a study-wide significant association for three SNPs with susceptibility for dyslexia. In summary, our results substantiate genetic markers in NEDD4L and MYO5B as risk factors for dyslexia and provide first evidence that the relevance of these markers is not restricted to the English language.
C1 [Mueller, B.; Czepezauer, I.; Quente, E.; Boltze, J.; Wilcke, A.; Kirsten, H.] Fraunhofer Inst Cell Therapy & Immunol, Dept Cell Therapy, D-04103 Leipzig, Germany.
[Ahnert, P.; Kirsten, H.] Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04109 Leipzig, Germany.
[Ahnert, P.; Kirsten, H.] Univ Leipzig, LIFE Ctr, Leipzig Interdisciplinary Res Cluster Genet Facto, D-04109 Leipzig, Germany.
[Burkhardt, J.; Boltze, J.; Wilcke, A.; Kirsten, H.] Univ Leipzig, Translat Ctr Regenerat Med TRM, D-04109 Leipzig, Germany.
[Brauer, J.] Max Planck Inst Human Cognit & Brain Sci, Dept Neuropsychol, Leipzig, Germany.
[Boltze, J.] Massachusetts Gen Hosp, Stroke & Neuro Vasc Regulat Lab, Boston, MA 02114 USA.
[Boltze, J.] Harvard Univ, Sch Med, Boston, MA USA.
RP Mueller, B (reprint author), Fraunhofer Inst Cell Therapy & Immunol, Dept Cell Therapy, Perlickstr 1, D-04103 Leipzig, Germany.
EM bent.mueller@izi.fraunhofer.de
RI Ahnert, Peter/I-8150-2015;
OI Ahnert, Peter/0000-0002-1771-0856; Muller, Bent/0000-0001-8308-6193
FU Federal Ministry of Education and Research [BMBF 1315883]; Leipzig
Interdisciplinary Research Cluster of Genetic Factors, Clinical
Phenotypes and Environment (LIFE Center, Universitat Leipzig); European
Union; European Regional Development Fund (ERFD); European Social Fund;
Free State of Saxony; Max-Planck Society; Fraunhofer Society program
('Pakt fur Forschung und Innovation', project 'LEGASCREEN')
FX E.Q., J.Bu., H.K. and A.W. received funding from the Federal Ministry of
Education and Research (BMBF 1315883). P.A. and H.K. were funded by the
Leipzig Interdisciplinary Research Cluster of Genetic Factors, Clinical
Phenotypes and Environment (LIFE Center, Universitat Leipzig). LIFE is
funded by means of the European Union, by the European Regional
Development Fund (ERFD), the European Social Fund and by means of the
Free State of Saxony within the framework of the excellence initiative.
Finally, B.M., J.Bo., J.Br., H.K., I.C. and A.W. received funding from
the joint Max-Planck Society and Fraunhofer Society program ('Pakt fur
Forschung und Innovation', project 'LEGASCREEN'). The authors declare no
conflict of interest.
NR 35
TC 3
Z9 3
U1 2
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1601-1848
EI 1601-183X
J9 GENES BRAIN BEHAV
JI Genes Brain Behav.
PD MAR
PY 2014
VL 13
IS 3
BP 350
EP 356
DI 10.1111/gbb.12118
PG 7
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA AB8ND
UT WOS:000332046400010
PM 24373531
ER
PT J
AU Dogliotti, A
Paolasso, E
Giugliano, RP
AF Dogliotti, Ariel
Paolasso, Ernesto
Giugliano, Robert P.
TI Current and new oral antithrombotics in nonvalvular atrial fibrillation:
a network meta-analysis of 79 808 patients
SO HEART
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; STROKE PREVENTION; DABIGATRAN ETEXILATE;
SECONDARY PREVENTION; ANTICOAGULANT DRUGS; ELDERLY-PATIENTS; DOSE
WARFARIN; ASPIRIN; RIVAROXABAN; APIXABAN
AB Background Antithrombotic therapy reduces stroke, embolism and mortality in patients with atrial fibrillation (AF); however, meta-analyses have focused on pairwise comparisons of treatments.
Objective To synthesise the evidence from trials using a multiple treatment comparison methods thereby permitting a broader comparison across multiple therapies.
Design, setting, patients Randomised controlled trials in patients with AF of antithrombotics were identified from MEDLINE, Embase, and Cochrane Central Register of Controlled Trials through May 2012. We performed a random-effects model within a Bayesian framework using Markov Chain Monte Carlo simulation to calculate pooled OR and 95% credibility intervals (CrI). We also ranked therapies by their likelihood of leading to the best results for the outcomes.
Main outcome measure Multiple endpoints including stroke, embolism, death and bleeding.
Results We identified 20 studies with 79808 patients allocated to 8 treatments: ASA, ASA plus clopidogrel, vitamin K antagonists (VKAs), dabigatran 110mg, dabigatran 150mg, rivaroxaban, apixaban or placebo/control. Compared with placebo/control, dabigatran 150mg was associated with the lowest risk of stroke (OR=0.25, 0.15-0.43), the composite of ischaemic stroke or systemic embolism (OR=0.26, 0.12-0.54) and mortality (OR=0.53, 0.28-0.88). ASA plus clopidogrel was associated with the highest risk of major bleeding (OR=3.65, 1.22-13.56). In simulated comparisons, the novel oral anticoagulants ranked better than VKA or antiplatelet therapies for prevention of stroke, ischaemic stroke or systemic embolism and mortality.
Conclusions In this network meta-analysis, novel oral anticoagulants were the most promising treatments to reduce stroke, stroke or systemic embolism, and all-cause mortality in patients with AF.
C1 [Dogliotti, Ariel] Grp Orono, Unidad Epidemiol Clin & Estadist, Rosario, Santa Fe, Argentina.
[Dogliotti, Ariel; Paolasso, Ernesto] Inst Cardiovasc Rosario, Rosario, Santa Fe, Argentina.
[Paolasso, Ernesto] Inst Invest Clin, Rosario, Santa Fe, Argentina.
[Giugliano, Robert P.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Giugliano, RP (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA.
EM rgiugliano@partners.org
FU Johnson Johnson; Daiichi-Sankyo
FX Robert Giugliano: Dr Giugliano is a member of the TIMI Study Group,
which has received research grant support from Johnson & Johnson and
from Daiichi-Sankyo related to clinical trials of anticoagulants. Dr
Giugliano has received honoraria for consultation/lectures from
Bristol-Myers Squibb, Daiichi-Sankyo and Johnson & Johnson.
NR 50
TC 26
Z9 26
U1 0
U2 4
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1355-6037
EI 1468-201X
J9 HEART
JI Heart
PD MAR 1
PY 2014
VL 100
IS 5
BP 396
EP 405
DI 10.1136/heartjnl-2013-304347
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AB8DV
UT WOS:000332021200011
PM 24009224
ER
PT J
AU Sondhi, D
Scott, EC
Chen, A
Hackett, NR
Wong, AMS
Kubiak, A
Nelvagal, HR
Pearse, Y
Cotman, SL
Cooper, JD
Crystal, RG
AF Sondhi, Dolan
Scott, Emma C.
Chen, Alvin
Hackett, Neil R.
Wong, Andrew M. S.
Kubiak, Agnieszka
Nelvagal, Hemanth R.
Pearse, Yewande
Cotman, Susan L.
Cooper, Jonathan D.
Crystal, Ronald G.
TI Partial Correction of the CNS Lysosomal Storage Defect in a Mouse Model
of Juvenile Neuronal Ceroid Lipofuscinosis by Neonatal CNS
Administration of an Adeno-Associated Virus Serotype rh. 10 Vector
Expressing the Human CLN3 Gene
SO HUMAN GENE THERAPY
LA English
DT Article
ID UNDERLYING BATTEN-DISEASE; KNOCK-IN MICE; GLIAL ACTIVATION; THERAPY;
BRAIN; PROTEIN; AUTOPHAGY; PATHOLOGY; JNCL; NEURODEGENERATION
AB Juvenile neuronal ceroid lipofuscinosis (JNCL or CLN3 disease) is an autosomal recessive lysosomal storage disease resulting from mutations in the CLN3 gene that encodes a lysosomal membrane protein. The disease primarily affects the brain with widespread intralysosomal accumulation of autofluorescent material and fibrillary gliosis, as well as the loss of specific neuronal populations. As an experimental treatment for the CNS manifestations of JNCL, we have developed a serotype rh.10 adeno-associated virus vector expressing the human CLN3 cDNA (AAVrh.10hCLN3). We hypothesized that administration of AAVrh.10hCLN3 to the Cln3(ex7/8) knock-in mouse model of JNCL would reverse the lysosomal storage defect, as well as have a therapeutic effect on gliosis and neuron loss. Newborn Cln3(ex7/8) mice were administered 3x10(10) genome copies of AAVrh.10hCLN3 to the brain, with control groups including untreated Cln3(ex7/8) mice and wild-type littermate mice. After 18 months, CLN3 transgene expression was detected in various locations throughout the brain, particularly in the hippocampus and deep anterior cortical regions. Changes in the CNS neuronal lysosomal accumulation of storage material were assessed by immunodetection of subunit C of ATP synthase, luxol fast blue staining, and periodic acid-Schiff staining. For all parameters, Cln3(ex7/8) mice exhibited abnormal lysosomal accumulation, but AAVrh.10hCLN3 administration resulted in significant reductions in storage material burden. There was also a significant decrease in gliosis in AAVrh.10hCLN3-treated Cln3(ex7/8) mice, and a trend toward improved neuron counts, compared with their untreated counterparts. These data demonstrate that AAVrh.10 delivery of a wild-type cDNA to the CNS is not harmful and instead provides a partial correction of the neurological lysosomal storage defect of a disease caused by a lysosomal membrane protein, indicating that this may be an effective therapeutic strategy for JNCL and other diseases in this category.
C1 [Sondhi, Dolan; Scott, Emma C.; Chen, Alvin; Hackett, Neil R.; Crystal, Ronald G.] Cornell Univ, Weill Med Coll, Dept Med Genet, New York, NY 10065 USA.
[Wong, Andrew M. S.; Kubiak, Agnieszka; Nelvagal, Hemanth R.; Pearse, Yewande; Cooper, Jonathan D.] Kings Coll London, Ctr Cellular Basis Behav, Dept Neurosci, London SE5 9NU, England.
[Wong, Andrew M. S.; Kubiak, Agnieszka; Nelvagal, Hemanth R.; Pearse, Yewande; Cooper, Jonathan D.] Kings Coll London, Inst Psychiat, Kings Hlth Partners Ctr Neurodegenerat Res, London SE5 9NU, England.
[Cotman, Susan L.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
RP Crystal, RG (reprint author), Cornell Univ, Weill Med Coll, Dept Med Genet, 1300 York Ave,Box 164, New York, NY 10065 USA.
EM geneticmedicine@med.cornell.edu
FU National Contest for Life-Stiftung; Natalie Fund; DEM-CHILD; European
Community [281234]; National Institutes of Health (National Institute of
Neurological Disorders Stroke) [R01-NS073813]; Dubai-Harvard Foundation
for Medical Research
FX We thank Benjamin Van de Graaf and Scott H. Coppel for technical
assistance and N. Mohamed and D. N. McCarthy for help in preparing this
article. The studies were supported, in part, by National Contest for
Life-Stiftung, The Natalie Fund, and DEM-CHILD funding from the European
Community's Seventh Framework Programme (FP7/2007-2013) under Grant
Agreement No. 281234. S. L. C. is supported by the National Institutes
of Health (National Institute of Neurological Disorders & Stroke;
R01-NS073813) and the Dubai-Harvard Foundation for Medical Research.
NR 63
TC 10
Z9 10
U1 0
U2 6
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 MAR 1
PY 2014
VL 25
IS 3
BP 223
EP 239
DI 10.1089/hum.2012.253
PG 17
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AC8FE
UT WOS:000332768100009
PM 24372003
ER
PT J
AU Kramer, J
Rubin, A
Coster, W
Helmuth, E
Hermos, J
Rosenbloom, D
Moed, R
Dooley, M
Kao, YC
Liljenquist, K
Brief, D
Enggasser, J
Keane, T
Roy, M
Lachowicz, M
AF Kramer, Jessica
Rubin, Amy
Coster, Wendy
Helmuth, Eric
Hermos, John
Rosenbloom, David
Moed, Rich
Dooley, Meghan
Kao, Ying-Chia
Liljenquist, Kendra
Brief, Deborah
Enggasser, Justin
Keane, Terence
Roy, Monica
Lachowicz, Mark
TI Strategies to address participant misrepresentation for eligibility in
Web-based research
SO INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH
LA English
DT Article
DE Internet data collection; World Wide Web data collection; sampling
methods; recruitment and enrollment methods; participant
misrepresentation
ID ALCOHOL-USE; PEDI-CAT; INTERNET; CARE
AB Emerging methodological research suggests that the World Wide Web (Web) is an appropriate venue for survey data collection, and a promising area for delivering behavioral intervention. However, the use of the Web for research raises concerns regarding sample validity, particularly when the Web is used for recruitment and enrollment. The purpose of this paper is to describe the challenges experienced in two different Web-based studies in which participant misrepresentation threatened sample validity: a survey study and an online intervention study. The lessons learned from these experiences generated three types of strategies researchers can use to reduce the likelihood of participant misrepresentation for eligibility in Web-based research. Examples of procedural/design strategies, technical/software strategies and data analytic strategies are provided along with the methodological strengths and limitations of specific strategies. The discussion includes a series of considerations to guide researchers in the selection of strategies that may be most appropriate given the aims, resources and target population of their studies. Copyright (c) 2014 John Wiley & Sons, Ltd.
C1 [Kramer, Jessica; Coster, Wendy; Dooley, Meghan; Kao, Ying-Chia; Liljenquist, Kendra] Boston Univ, Dept Occupat Therapy, Boston, MA 02215 USA.
[Rubin, Amy; Hermos, John] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Helmuth, Eric; Rosenbloom, David] Boston Univ, Dept Hlth Policy & Management, Boston, MA 02215 USA.
[Brief, Deborah; Enggasser, Justin; Keane, Terence; Roy, Monica; Lachowicz, Mark] VA Boston Healthcare Syst, Boston, MA USA.
RP Kramer, J (reprint author), Boston Univ, Dept Occupat Therapy, 635 Commonwealth Ave SAR 503, Boston, MA 02215 USA.
EM kramerj@bu.edu
FU NIAAA NIH HHS [RC1 AA019248]; NICHD NIH HHS [R21 HD065281]
NR 19
TC 11
Z9 11
U1 2
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1049-8931
EI 1557-0657
J9 INT J METH PSYCH RES
JI Int. J. Methods Psychiatr. Res.
PD MAR
PY 2014
VL 23
IS 1
BP 120
EP 129
DI 10.1002/mpr.1415
PG 10
WC Psychiatry
SC Psychiatry
GA AD1QZ
UT WOS:000333009800011
PM 24431134
ER
PT J
AU Yehia, BR
French, B
Fleishman, JA
Metlay, JP
Berry, SA
Korthuis, PT
Agwu, AL
Gebo, KA
AF Yehia, Baligh R.
French, Benjamin
Fleishman, John A.
Metlay, Joshua P.
Berry, Stephen A.
Korthuis, P. Todd
Agwu, Allison L.
Gebo, Kelly A.
CA HIV Res Network
TI Retention in Care Is More Strongly Associated With Viral Suppression in
HIV-Infected Patients With Lower Versus Higher CD4 Counts
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE HIV disease severity; viral suppression; engagement in care; retention
in care; retention measures; CD4 count
ID ACTIVE ANTIRETROVIRAL THERAPY; MEDICAL-CARE; ADHERENCE; COHORT;
PREDICTORS; PREVENTION; SURVIVAL; OUTCOMES; FAILURE; CLINICS
AB Background: Retention in care is important for all HIV-infected patients, but may be more important for people with advanced HIV disease. We evaluated whether the association between retention in care and viral suppression differed by HIV disease severity. Methods: A repeated cross-sectional analysis (2006-2011) involving 35,433 adults at 18 US HIV clinics. Multivariable logistic regression models examined associations between retention measures [Health Resources and Services Administration (HRSA) retention measure, 6-month gap, and 3-month visit constancy] and viral suppression (HIV-1 RNA <= 400 copies/mL) for HIV disease severity groups defined by CD4 counts: <= 200, 201-350, 351-500, and >500 cells per cubic millimeter. Results: Overall, patients met the HRSA measure in 84% of person-years, did not have a 6-month gap in 76%, and had visits in all 4 quarters in 37%; patients achieved viral suppression in 72% of person-years. The association between retention in care and viral suppression differed by disease severity, and was strongest for patients with lower CD4 counts: <= 200 [adjusted odds ratio (AOR) = 2.33, 95% confidence interval (CI): 2.16 to 2.51], 201-350 (AOR = 1.96, CI: 1.81 to 2.12), 351-500 (AOR = 1.65, CI: 1.53 to 1.78), and >500 cells per cubic millimeter (AOR = 1.22, CI: 1.14 to 1.30) using the HRSA retention measure as a representative example. Conclusions: This is one of the first studies to report the impact of HIV disease severity on retention in care and viral suppression, demonstrating that retention in care is more strongly associated with viral suppression in patients with lower CD4 counts. These results have important implications for improving the health of patients with advanced HIV disease and for test and treat approaches to HIV prevention.
C1 [Yehia, Baligh R.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Yehia, Baligh R.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA.
[Yehia, Baligh R.] Philadelphia Vet Affairs Ctr Hlth Equ Res & Promo, Philadelphia, PA USA.
[French, Benjamin] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Fleishman, John A.] Agcy Healthcare Res & Qual, Ctr Financing Access & Cost Trends, Rockville, MD USA.
[Metlay, Joshua P.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Berry, Stephen A.; Agwu, Allison L.; Gebo, Kelly A.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Korthuis, P. Todd] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA.
RP Yehia, BR (reprint author), Univ Penn, Dept Med, Perelman Sch Med, 1021 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA.
EM byehia@upenn.edu
FU Agency for Healthcare Research and Quality [HHSA290201100007C]; National
Institutes of Health [K23-MH097647]
FX Supported by the Agency for Healthcare Research and Quality
(HHSA290201100007C) and the National Institutes of Health (K23-MH097647
to B.R.Y.).
NR 34
TC 21
Z9 21
U1 2
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD MAR 1
PY 2014
VL 65
IS 3
BP 333
EP 339
DI 10.1097/QAI.0000000000000023
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA AH0DL
UT WOS:000335789200023
PM 24129370
ER
PT J
AU Marks, KM
Kitch, D
Chung, RT
Hadigan, C
Andersen, J
Tien, P
Luetkemeyer, A
Alston-Smith, B
Glesby, MJ
AF Marks, Kristen M.
Kitch, Douglas
Chung, Raymond T.
Hadigan, Colleen
Andersen, Janet
Tien, Phyllis
Luetkemeyer, Annie
Alston-Smith, Beverly
Glesby, Marshall J.
CA A5239 Team
TI Pilot Study of Pioglitazone Before HCV Retreatment in HIV/HCV Genotype
1-Infected Subjects With Insulin Resistance and Previous Nonresponse to
Peginterferon and Ribavirin Therapy: A5239
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE metabolic; hepatitis C; nonresponder; pegylated interferon; insulin
resistance; HIV
ID HEPATITIS-C VIRUS; ALPHA-2A PLUS RIBAVIRIN; VIROLOGICAL RESPONSE;
COINFECTED PATIENTS; NONALCOHOLIC STEATOHEPATITIS; ANTIRETROVIRAL
THERAPY; INFECTED PATIENTS; HIV; STEATOSIS; METFORMIN
AB Insulin resistance is associated with nonresponse to hepatitis C virus (HCV) treatment. In this multicenter, single-arm pilot study, adult, HIV/HCV genotype 1-coinfected previous nonresponders to peginterferon/ribavirin (PegIFN/RBV) with homeostatic model assessment of insulin resistance >2.5 were treated with pioglitazone (PIO) for 24 weeks followed by PegIFN/RBV/PIO. Three of 19 subjects (15.8%) achieved undetectable HCV RNA at week 24 of PegIFN/RBV/PIO, which was not significantly different than the historical null rate of 10% (P = 0.29, lower limit of the exact 1-sided 90% confidence interval 5.9%). Over the 24 weeks of PIO monotherapy, alanine aminotransferase and aspartate aminotransferase declined significantly and correlated with improved metabolic parameters.
C1 [Marks, Kristen M.; Glesby, Marshall J.] Weill Cornell Med Coll, Div Infect Dis, New York, NY 10065 USA.
[Kitch, Douglas; Andersen, Janet] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Div, Boston, MA USA.
[Hadigan, Colleen; Alston-Smith, Beverly] NIAID, NIH, Bethesda, MD 20892 USA.
[Tien, Phyllis] Univ Calif San Francisco, Sch Med, Div Infect Dis, San Francisco, CA USA.
[Tien, Phyllis] Dept Vet Affairs, Med Serv, San Francisco, CA USA.
[Luetkemeyer, Annie] Univ Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA USA.
RP Marks, KM (reprint author), Weill Cornell Med Coll, Div Infect Dis, 525 East 68th St,F24, New York, NY 10065 USA.
EM markskr@med.cornell.edu
FU National Institute of Allergy and Infectious Diseases [UM1AI068636];
National Institute of Mental Health, National Institute of Dental and
Craniofacial Research; Roche (Genentech); Takeda Pharmaceuticals, USA,
Inc.; AACTG/ACTG Statistical and Data Management Center [1 UM1 AI068634,
5 U01 AI38855]; Intramural National Institute of Allergy and Infectious
Diseases support [NIH DK078772, K24 AI078884, U01 AI069502]; Roche
Laboratories; Bristol-Myers Squibb; Gilead; Vertex Pharmaceuticals;
Pfizer; Gilead Sciences; SIGA Technologies; Boehringer Ingelheim; CTU
[U01 AI69419, 5UO1 AI069502-07, UM1AI069532, UM1 AI069511, AI69501, AI
069471, UM1-AI069503, IU0IAI69472]; CTSCs from the National Center for
Advancing Translational Sciences component of the National Institutes of
Health (NIH) [UL1 TR000457, UL1TR000439]; National Center for Advancing
Translational Sciences (Virginia Commonwealth University) [UL1TR000058]
FX Supported by Award Number UM1AI068636 from the National Institute of
Allergy and Infectious Diseases and supported by National Institute of
Mental Health, National Institute of Dental and Craniofacial Research.
This research was also supported by Roche (Genentech) and Takeda
Pharmaceuticals, USA, Inc. Other grant support included 1 UM1 AI068634
and 5 U01 AI38855 to AACTG/ACTG Statistical and Data Management Center;
Intramural National Institute of Allergy and Infectious Diseases support
(C. H.); NIH DK078772 (R. T. C.); K24 AI078884 (M. G.), U01 AI069502 (A.
L.). R. T. C. received research funding from Roche Laboratories. A. L.
has received research grant support to University of California San
Francisco from Bristol-Myers Squibb, Gilead, and Vertex Pharmaceuticals.
M.J.G. has received research support from Pfizer to Weill Cornell
Medical College and has served as a consultant to Gilead Sciences, SIGA
Technologies, and Pfizer. K. M. M. has received research support to
Weill Cornell Medical College from Bristol-Myers Squibb, Vertex
Pharmaceuticals, Janssen Pharmaceuticals, Boehringer Ingelheim, and
Gilead and has received honoraria for lectures from Boehringer Ingelheim
and Bristol-Myers Squibb. Also supported in part by CTU grants,
including U01 AI69419 [Cornell (Site 7804)], 5UO1 AI069502-07
[University of California San Francisco AIDS CRS (Site 801)],
UM1AI069532 [New York University/NYC HHC at Bellevue Hospital Center
(Site 401)], UM1 AI069511 [University of Rochester (Site 1101)], AI69501
[MetroHealth Medical Center (Site 2503)], AI 069471 [Northwestern
University (A2701)], UM1-AI069503 [Virginia Commonwealth University
(Site 31475)], and Massachusetts General Hospital (Site 101) CTU Grant
IU0IAI69472. Also supported in part by grants funded by site CTSCs,
including UL1 TR000457 (Cornell CTSC), UL1TR000439 from the National
Center for Advancing Translational Sciences component of the National
Institutes of Health (NIH) and NIH roadmap for Medical Research
(Clinical and Translational Science Collaborative of Cleveland),
UL1TR000058 from the National Center for Advancing Translational
Sciences (Virginia Commonwealth University).
NR 19
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD MAR 1
PY 2014
VL 65
IS 3
BP 345
EP 349
DI 10.1097/QAI.0000000000000073
PG 5
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA AH0DL
UT WOS:000335789200025
PM 24525470
ER
PT J
AU Desmonde, S
Essanin, JB
Aka, AE
Messou, E
Amorissani-Folquet, M
Rondeau, V
Ciaranello, A
Leroy, V
AF Desmonde, Sophie
Essanin, Jean-Bosco
Aka, Addi E.
Messou, Eugene
Amorissani-Folquet, Madeleine
Rondeau, Virginie
Ciaranello, Andrea
Leroy, Valeriane
TI Morbidity and Health care Resource Utilization in HIV-Infected Children
After Antiretroviral Therapy Initiation in Cote d'Ivoire, 2004-2009
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE morbidity; HIV; antiretroviral therapy; health care resource
utilization; children; West Africa
ID MALARIA-ENDEMIC AREA; FOLLOW-UP; COTRIMOXAZOLE PROPHYLAXIS;
HIV-1-INFECTED CHILDREN; HOSPITAL ADMISSIONS; TREATMENT PROGRAM; ZAMBIAN
CHILDREN; LIMITED SETTINGS; WEST-AFRICA; ABIDJAN
AB Background: We describe severe morbidity and health care resource utilization (HCRU) among HIV-infected children on antiretroviral therapy (ART) in Abidjan, Cote d ' Ivoire. Methods: All HIV-infected children enrolled in an HIV-care program (2004-2009) were eligible for ART initiation until database closeout, death, ART interruption, or loss to follow-up. We calculated incidence rates (IRs) of density per 100 child-years (CYs) for severe morbidity, HCRU (outpatient care and inpatient care), and associated factors using frailty models with a Weibull distribution. Results: Of 332 children with a median age of 5.7 years and median follow-up of 2.5 years, 65.4% were severely immunodeficient by World Health Organization (WHO) criteria, and all received cotrimoxazole prophylaxis. We recorded 464 clinical events in 228 children; the overall IR was 57.6/100 CYs [95% confidence interval (CI): 52.1 to 62.5]. Severe morbidity was more frequent in children on protease inhibitor (PI)-based ART compared to those on other regimens [adjusted hazards ratio (aHR): 1.83; 95% CI: 1.35 to 2.47] and to those moderately/severely immunodeficient compared to those not (aHR: 1.57; 95% CI: 1.13 to 2.18 and aHR: 2.53; 95% CI: 1.81 to 3.55, respectively). Of the 464 events, 371 (80%) led to outpatient care (IR: 45.6/100 CYs) and 164 (35%) to inpatient care (IR: 20.2/100 CYs). In adjusted analyses, outpatient care was significantly less frequent in children older than 10 years compared with children younger than 2 years (aHR: 0.49; 95% CI: 0.31 to 0.78) and in those living furthest from clinics compared with those living closest (aHR: 0.65; 95% CI: 0.47 to 0.90). Both inpatient and outpatient HCRU were negatively associated with cotrimoxazole prophylaxis. Conclusions: Despite ART, HIV-infected children still require substantial utilization of health care services.
C1 [Desmonde, Sophie; Rondeau, Virginie; Leroy, Valeriane] Ctr INSERM U897, Bordeaux, France.
[Desmonde, Sophie; Rondeau, Virginie; Leroy, Valeriane] Univ Bordeaux, ISPED, Ctr INSERM U897, Bordeaux, France.
[Essanin, Jean-Bosco; Amorissani-Folquet, Madeleine] Univ Cocody, Abidjan, Cote Ivoire.
[Aka, Addi E.; Messou, Eugene] ACONDA, CePReF, Abidjan, Cote Ivoire.
[Amorissani-Folquet, Madeleine] Cocody Univ Hosp, Dept Pediat, Abidjan, Cote Ivoire.
[Ciaranello, Andrea] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Desmonde, S (reprint author), INSERM, U897, ISPED, F-33076 Bordeaux, France.
EM sophie.desmonde@isped.u-bordeaux2.fr
RI Leroy, Valeriane/F-8129-2013; rondeau, virginie/E-4192-2014
OI Leroy, Valeriane/0000-0003-3542-8616; rondeau,
virginie/0000-0001-7109-4831
FU National Cancer Institute; Eunice Kennedy Shriver National Institute of
Child Health and Human Development (NICHD); National Institute of
Allergy and Infectious Diseases (NIAID) of the US National Institutes of
Health [U01AI069919, R01 A1058736, R01AI05873, K01AI078754];
International Maternal Pediatric Adolescent AIDS Clinical Trials
network; NIAID [U01 AI068632]; NICHD; National Institute of Mental
Health [AI068632]; United States President's Emergency Plan for AIDS
Relief, through the Elizabeth Glaser Pediatric AIDS Foundation,
Washington, DC; French GIP ESTHER; Cote d'Ivoire Ministry of Public
Health
FX Supported in part by the National Cancer Institute, the Eunice Kennedy
Shriver National Institute of Child Health and Human Development
(NICHD), and the National Institute of Allergy and Infectious Diseases
(NIAID) of the US National Institutes of Health, Grants U01AI069919
(Epidemiologic Databases to Evaluate AIDS, West Africa), R01 A1058736,
R01AI05873, and K01AI078754, and the International Maternal Pediatric
Adolescent AIDS Clinical Trials network (A. C.). Overall support for
International Maternal Pediatric Adolescent AIDS Clinical Trials was
provided by the NIAID Grant U01 AI068632, the NICHD, and the National
Institute of Mental Health Grant AI068632. S. D. is a fellow of the
Ecole des Hautes Etudes en Sante Publique, Rennes, France. The Aconda
program was funded by the United States President's Emergency Plan for
AIDS Relief, through the Elizabeth Glaser Pediatric AIDS Foundation,
Washington, DC, with additional support from the French GIP ESTHER and
the Cote d'Ivoire Ministry of Public Health.
NR 46
TC 2
Z9 2
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD MAR 1
PY 2014
VL 65
IS 3
BP E95
EP E103
DI 10.1097/QAI.0b013e3182a4ea6f
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA AH0DL
UT WOS:000335789200001
PM 24525473
ER
PT J
AU Thrift, AP
Kramer, JR
Alsarraj, A
El-Serag, HB
AF Thrift, Aaron P.
Kramer, Jennifer R.
Alsarraj, Abeer
El-Serag, Hashem B.
TI Fat Mass by Bioelectrical Impedance Analysis is not Associated With
Increased Risk of Barrett Esophagus
SO JOURNAL OF CLINICAL GASTROENTEROLOGY
LA English
DT Article
DE Barrett esophagus; obesity; bioelectrical impedance analysis; risk
factors
ID APPENDICULAR BODY-COMPOSITION; BIOIMPEDANCE ANALYSIS;
GENERAL-POPULATION; ABDOMINAL OBESITY; INDEX; ADIPOSITY; ACCURACY;
ADENOCARCINOMA; METAANALYSIS; ADULTS
AB Goal:To evaluate whether the association between obesity and Barrett esophagus (BE) is due to total body fatness, abdominal obesity, or both.Background:BE risk seems to be more strongly related to central obesity than total obesity. However, no studies have investigated the association between total obesity and BE using direct measures of total body fatness.Study:We conducted a case-control study among patients scheduled for elective esophagogastroduodenoscopy, and a sample of patients eligible for screening colonoscopy recruited from primary care clinics. BE cases were patients with specialized intestinal metaplasia, whereas controls had no endoscopic or histopathologic BE. All patients underwent a study esophagogastroduodenoscopy and had body measurements taken. Fat mass and fat-free mass were estimated from bioelectrical impedance analysis (BIA). We calculated odds ratios (OR) and 95% confidence intervals (95% CI) using multivariable logistic regression.Results:There were 70 BE cases, 229 endoscopy controls, and 118 primary care controls. BMI and BIA-derived fat mass were highly correlated; however, we found no association between BMI, fat mass, and BE (vs. all controls: BMI, OR/1 SD=1.01; 95% CI, 0.76-1.34; fat mass, OR=1.02; 95% CI, 0.77-1.36). Waist-to-hip ratio was significantly associated with increased BE risk (vs. all controls: OR/1 SD=1.45; 95% CI, 1.03-2.04). We found similar results when we analyzed the control groups separately.Conclusion:Waist-to-hip ratio, but not fat mass or BMI, was associated with increased BE risk. This study provides strong evidence that BE is related to body size and composition through central adiposity and not through total body fatness.
C1 [Thrift, Aaron P.] Queensland Inst Med Res, Dept Populat Hlth, Brisbane, Qld 4006, Australia.
[Kramer, Jennifer R.; Alsarraj, Abeer; El-Serag, Hashem B.] Baylor Coll Med, Houston VA HSR&D Ctr Excellence, Houston, TX 77030 USA.
[El-Serag, Hashem B.] Baylor Coll Med, Dept Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA.
[Kramer, Jennifer R.] Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA.
[El-Serag, Hashem B.] Baylor Coll Med, Dept Med, Sect Gastroenterol & Hepatol, Houston, TX 77030 USA.
RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr, 2002 Holcombe Blvd 152, Houston, TX 77030 USA.
EM hasheme@bcm.edu
FU NIH [NCI R01 116845]; Houston VA, HSR&D Center of Excellence
[HFP90-020]; Texas Digestive Disease Center NIH [DK58338]; NIDDK
[K24-04-107]
FX Supported in part by NIH grant NCI R01 116845, the Houston VA, HSR&D
Center of Excellence (HFP90-020), and the Texas Digestive Disease Center
NIH, DK58338. H.B.E.-S. is also supported by NIDDK K24-04-107.
NR 28
TC 8
Z9 8
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0192-0790
EI 1539-2031
J9 J CLIN GASTROENTEROL
JI J. Clin. Gastroenterol.
PD MAR
PY 2014
VL 48
IS 3
BP 218
EP 223
DI 10.1097/MCG.0b013e31829ae98c
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AF7UU
UT WOS:000334921100004
PM 23842216
ER
PT J
AU Jin, J
Machado, ER
Yu, H
Zhang, X
Lu, Z
Li, Y
Lopes-Virella, MF
Kirkwood, KL
Huang, Y
AF Jin, J.
Machado, E. R.
Yu, H.
Zhang, X.
Lu, Z.
Li, Y.
Lopes-Virella, M. F.
Kirkwood, K. L.
Huang, Y.
TI Simvastatin Inhibits LPS-induced Alveolar Bone Loss during Metabolic
Syndrome
SO JOURNAL OF DENTAL RESEARCH
LA English
DT Article
DE lipopolysaccharide; inflammation obesity; periodontal disease; statin;
insulin resistance
ID PERIODONTAL-DISEASE; STATIN THERAPY; CARDIOVASCULAR-DISEASE; TNF-ALPHA;
OBESITY; INFLAMMATION; ASSOCIATION; METAANALYSIS; ARTHRITIS; MICE
AB Studies in recent years have shown a positive relationship between metabolic syndrome (MS) and periodontal disease (PD). Given that patients with MS take statins to reduce cholesterol, and statins also have anti-inflammatory effects, it is important to determine if statin intake hinders the progression of MS-associated PD. In this study, PD was induced in Zucker fat rats (ZFRs), an animal model for MS, and in control lean rats by periodontal injection of Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS), while simvastatin was given to some of the rats via gavage. After 4 wk of treatment, alveolar bone loss was determined by micro-computed tomography. To explore the underlying mechanisms, we determined the effect of simvastatin on tissue inflammation and the expression of molecules involved in osteoclastogenesis. Results showed that while bone loss was increased by LPS in both ZFRs and the control lean rats, it was significantly more in the former than the latter. Simvastatin effectively alleviated bone loss in both ZFRs and the control rats. Results also showed that LPS stimulated leukocyte tissue infiltration and expression of molecules for osteoclastogenesis, but simvastatin significantly modulated the stimulation. This study demonstrated that simvastatin inhibited LPS-induced alveolar bone loss and periodontal tissue inflammation in rats with MS.
C1 [Jin, J.; Zhang, X.; Lu, Z.; Li, Y.; Lopes-Virella, M. F.; Huang, Y.] Med Univ S Carolina, Coll Med, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA.
[Lopes-Virella, M. F.; Huang, Y.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
[Machado, E. R.; Yu, H.; Kirkwood, K. L.] Med Univ S Carolina, Coll Dent Med, Dept Craniofacial Biol, Charleston, SC 29425 USA.
[Machado, E. R.; Yu, H.; Kirkwood, K. L.] Med Univ S Carolina, Coll Dent Med, Ctr Oral Hlth Res, Charleston, SC 29425 USA.
[Jin, J.] Guilin Med Univ, Affiliated Hosp, Lab Hepatobiliary & Pancreat Surg, Guilin 541001, Guangxi, Peoples R China.
RP Huang, Y (reprint author), Med Univ S Carolina, Coll Med, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA.
EM huangyan@musc.edu
FU National Institutes of Health [DE016353]; Biomedical Laboratory Research
and Development Program of the Department of Veterans Affairs; National
Institute of General Medical Sciences of the National Institutes of
Health [P30103331]
FX This work was supported by National Institutes of Health grant DE016353
and by the Biomedical Laboratory Research and Development Program of the
Department of Veterans Affairs (to Y.H.). Research reported in this
publication was also supported by an Institutional Development Award
(IDeA) from the National Institute of General Medical Sciences of the
National Institutes of Health under grant number P30103331. The authors
declare no potential conflicts of interest with respect to the
authorship and/or publication of this article.
NR 30
TC 8
Z9 9
U1 1
U2 7
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 MAR
PY 2014
VL 93
IS 3
BP 294
EP 299
DI 10.1177/0022034513516980
PG 6
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA AA9SM
UT WOS:000331433200013
PM 24352501
ER
PT J
AU Nunn, ME
Fish, MD
Garcia, RI
Kaye, EK
Figueroa, R
Gohel, A
Ito, M
Lee, HJ
Williams, DE
Miyamoto, T
AF Nunn, M. E.
Fish, M. D.
Garcia, R. I.
Kaye, E. K.
Figueroa, R.
Gohel, A.
Ito, M.
Lee, H. J.
Williams, D. E.
Miyamoto, T.
TI Response to Letter to the Editor, "Retained Asymptomatic Third Molars
and Risk for Second Molar Pathology"
SO JOURNAL OF DENTAL RESEARCH
LA English
DT Letter
C1 [Nunn, M. E.; Miyamoto, T.] Creighton Univ, Sch Dent, Dept Periodontol, Omaha, NE 68178 USA.
[Fish, M. D.; Garcia, R. I.; Kaye, E. K.] Boston Univ, Henry M Goldman Sch Dent Med, Dept Hlth Policy & Hlth Serv Res, Boston, MA 02215 USA.
[Garcia, R. I.] VA Boston Healthcare Syst, Boston, MA USA.
[Figueroa, R.] Boston Univ, Henry M Goldman Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02215 USA.
[Gohel, A.] Boston Univ, Henry M Goldman Sch Dent Med, Dept Oral & Maxillofacial Radiol, Boston, MA 02215 USA.
[Ito, M.] Nihon Univ, Sch Dent Matsudo, Dept Removable Prosthodont, Chiba, Japan.
[Lee, H. J.] Seoul Natl Univ, Bundang Hosp, Dept Periodontol, Songnam, South Korea.
[Williams, D. E.] Creighton Univ, Sch Dent, Dept Oral & Maxillofacial Surg, Omaha, NE 68178 USA.
RP Nunn, ME (reprint author), Creighton Univ, Sch Dent, Dept Periodontol, Omaha, NE 68178 USA.
EM nunn@creighton.edu
FU NIDCR NIH HHS [R01 DE019656, K24 DE000419]
NR 5
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0022-0345
EI 1544-0591
J9 J DENT RES
JI J. Dent. Res.
PD MAR
PY 2014
VL 93
IS 3
BP 320
EP 321
DI 10.1177/0022034513520327
PG 2
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA AA9SM
UT WOS:000331433200018
PM 24554649
ER
PT J
AU Zhao, PC
Hou, LF
Farley, K
Sundrud, MS
Remold-O'Donnell, E
AF Zhao, Picheng
Hou, Lifei
Farley, Kalamo
Sundrud, Mark S.
Remold-O'Donnell, Eileen
TI SerpinB1 regulates homeostatic expansion of IL-17(+) gamma delta and
CD4(+)Th17 cells
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Article
DE lymphocytes; population size; cell proliferation; inflammation; cytokine
regulation
ID SERINE-PROTEASE INHIBITORS; T-CELLS; INFLUENZA-A; TRANSCRIPTION FACTOR;
INTERFERON-GAMMA; INFECTION; IDENTIFICATION; LYMPHOCYTES; MECHANISM;
INFLAMMATION
AB Gene-deleted mice show that serpinB1 serves as an endogenous restraint to limit untoward expansion of lymphocytes with a Th17 phenotype. SerpinB1 is an endogenous inhibitor of serine proteases recognized for its anti-inflammatory and host-protective properties. Although loss of serpinB1 in mice does not result in gross immune deregulation, serpinb1a(-/-) mice display increased mortality and inflammation-associated morbidity upon challenge with influenza virus. Here, we show that IL-17A(+) and CD4(+) Th17 cells are already expanded in the lungs of serpinb1a(-/-) mice at steady-state. Both and (+) CD4(+) CCR6(+) T cells isolated from the lungs of naive serpinb1a(-/-) mice displayed a skewed transcriptional profile relative to WT cells, including increased Th17 signature transcripts [Il17a, l17f, and Rorc (RORt)] and decreased Th1 signature transcripts [Ifng, Cxcr3, and Tbx21 (T-bet)] in T cells. In addition to the lung, IL-17A(+) and CD4(+) Th17 cells were increased in the spleen of naive serpinb1a(-/-) mice, despite normal and T cell development in the thymus. Within the T cell compartment, loss of serpinb1a prompted selective expansion of V4(+) and V6/V1(+) cells, which also displayed elevated expression of the proliferating cell nuclear antigen, Ki-67, and IL-17A. Given that serpinb1a is preferentially expressed in WT IL-17A(+) and CD4(+) Th17 cell subsets vis-a-vis other T cell lineages, our findings reveal a novel function of serpinB1 in limiting untoward expansion of lymphocytes with a Th17 phenotype.
C1 [Zhao, Picheng; Hou, Lifei; Farley, Kalamo; Remold-O'Donnell, Eileen] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Remold-O'Donnell, Eileen] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Zhao, Picheng; Hou, Lifei; Farley, Kalamo; Remold-O'Donnell, Eileen] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Sundrud, Mark S.] Tempero Pharmaceut, Discovery Biol, Cambridge, MA USA.
RP Remold-O'Donnell, E (reprint author), Boston Childrens Hosp, 3 Blackfan Circle, Boston, MA 02115 USA.
EM eileen.remold-odonnell@childrens.harvard.edu
RI ZHAO, PICHENG/G-3737-2014
FU Pilot Award of the GlaxoSmithKline/Immune Disease Institute Research
Alliance; National Heart, Lung, and Blood Institute, U.S. National
Institutes of Health, Bethesda, MD, USA [HL-066548]
FX This work was supported by a Pilot Award of the GlaxoSmithKline/Immune
Disease Institute Research Alliance and by grant HL-066548 from the
National Heart, Lung, and Blood Institute, U.S. National Institutes of
Health, Bethesda, MD, USA. We thank Kevan L. Hartshorn and Mitchell
White (Boston Medical Center, Boston, MA, USA) for providing virus;
Robert Tigelaar and Julie Lewis (Yale University School of Medicine, New
Haven, CT, USA) for 17D1 antibodies; Natasha Barteneva PCMM Flow
Cytometry Core Facility, Boston, MA, USA] for guidance in cell sorting;
and Scott Davis (Tempero Pharmaceuticals, Cambridge, MA, USA) for
technical support with microarray data analyses. We thank Jessica Cooley
for figure preparation and Fauve Dela Cruz for maintaining the mouse
colony.
NR 43
TC 10
Z9 12
U1 0
U2 2
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0741-5400
EI 1938-3673
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD MAR
PY 2014
VL 95
IS 3
BP 521
EP 530
DI 10.1189/jlb.0613331
PG 10
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA AG3MU
UT WOS:000335324400015
PM 24249741
ER
PT J
AU Crabtree, D
Dodson, M
Ouyang, XS
Boyer-Guittaut, M
Liang, QL
Ballestas, ME
Fineberg, N
Zhang, JH
AF Crabtree, Donna
Dodson, Matthew
Ouyang, Xiaosen
Boyer-Guittaut, Michael
Liang, Qiuli
Ballestas, Mary E.
Fineberg, Naomi
Zhang, Jianhua
TI Over-expression of an inactive mutant cathepsin D increases endogenous
alpha-synuclein and cathepsin B activity in SH-SY5Y cells
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE autophagy; cathepsin D; lysosome; alpha-synuclein
ID CHAPERONE-MEDIATED AUTOPHAGY; FAMILIAL PARKINSONS-DISEASE; LYSOSOMAL
STORAGE; IN-VIVO; MACROAUTOPHAGY; DEGRADATION; AGGREGATION; DUPLICATION;
TOXICITY; NEURONS
AB Parkinson's disease is a neurodegenerative movement disorder. The histopathology of Parkinson's disease comprises proteinaceous inclusions known as Lewy bodies, which contains aggregated -synuclein. Cathepsin D (CD) is a lysosomal protease previously demonstrated to cleave -synuclein and decrease its toxicity in both cell lines and mouse brains in vivo. Here, we show that pharmacological inhibition of CD, or introduction of catalytically inactive mutant CD, resulted in decreased CD activity and increased cathepsin B activity, suggesting a possible compensatory response to inhibition of CD activity. However, this increased cathepsin B activity was not sufficient to maintain -synuclein degradation, as evidenced by the accumulation of endogenous -synuclein. Interestingly, the levels of LC3, LAMP1, and LAMP2, proteins involved in autophagy-lysosomal activities, as well as total lysosomal mass as assessed by LysoTracker flow cytometry, were unchanged. Neither autophagic flux nor proteasomal activities differs between cells over-expressing wild-type versus mutant CD. These observations point to a critical regulatory role for that endogenous CD activity in dopaminergic cells in -synuclein homeostasis which cannot be compensated for by increased Cathepsin B. These data support the potential need to enhance CD function in order to attenuate -synuclein accumulation as a therapeutic strategy against development of synucleinopathy.
C1 [Crabtree, Donna; Dodson, Matthew; Ouyang, Xiaosen; Boyer-Guittaut, Michael; Liang, Qiuli; Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA.
[Dodson, Matthew; Ouyang, Xiaosen; Boyer-Guittaut, Michael; Liang, Qiuli; Zhang, Jianhua] Univ Alabama Birmingham, Ctr Free Rad Biol, Birmingham, AL 35294 USA.
[Ouyang, Xiaosen; Liang, Qiuli; Zhang, Jianhua] Birmingham VA Med Ctr, Dept Vet Affairs, Birmingham, AL USA.
[Boyer-Guittaut, Michael] Univ Franche Comte, Biochim Lab, UFR Sci & Tech, F-25030 Besancon, France.
[Ballestas, Mary E.] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL 35294 USA.
[Fineberg, Naomi] UAB Sch Publ Hlth, Dept Biostat, Birmingham, AL USA.
RP Zhang, JH (reprint author), Univ Alabama Birmingham, Dept Pathol, BMRII 534,901 19th St S, Birmingham, AL 35294 USA.
EM zhanja@uab.edu
OI Ballestas, Mary/0000-0003-0660-9477; Zhang, Jianhua/0000-0002-2128-9574
FU Michael J Fox Foundation [NIHR01-NS064090]; VA merit award; UAB
Neuroscience NINDS Protein Interaction Core C [NINDSP30-NS047466]; NIH
[P30 AR48311]
FX We are grateful to Dr Aimee Landar, Ms Stephanie Wall, Victor
Darley-Usmar and members of the Zhang laboratory for technical help and
discussions. This study was supported by Michael J Fox Foundation,
NIHR01-NS064090 and a VA merit award (to JZ), NINDSP30-NS047466 (UAB
Neuroscience NINDS Protein Interaction Core C), and NIH P30 grant #P30
AR48311 (RDCC-APCC core). The authors have no conflict of interest to
declare.
NR 33
TC 14
Z9 14
U1 1
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD MAR
PY 2014
VL 128
IS 6
BP 950
EP 961
DI 10.1111/jnc.12497
PG 12
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA AC2PV
UT WOS:000332347300016
PM 24138030
ER
PT J
AU Pietersen, CY
Mauney, SA
Kim, SS
Lim, MP
Rooney, RJ
Goldstein, JM
Petryshen, TL
Seidman, LJ
Shenton, ME
McCarley, RW
Sonntag, KC
Woo, TUW
AF Pietersen, Charmaine Y.
Mauney, Sarah A.
Kim, Susie S.
Lim, Maribel P.
Rooney, Robert J.
Goldstein, Jill M.
Petryshen, Tracey L.
Seidman, Larry J.
Shenton, Martha E.
McCarley, Robert W.
Sonntag, Kai-C.
Woo, Tsung-Ung W.
TI Molecular Profiles of Pyramidal Neurons in the Superior Temporal Cortex
in Schizophrenia
SO JOURNAL OF NEUROGENETICS
LA English
DT Article
DE cerebral cortex; gene expression profiling; laser-capture
microdissection; microRNA; schizophrenia
ID CHONDROITIN SULFATE PROTEOGLYCANS; LASER-CAPTURE MICRODISSECTION;
DENDRITIC SPINE DENSITY; GROWTH-FACTOR-BETA; REAL-TIME PCR; GRAY-MATTER
ABNORMALITIES; PREFRONTAL CORTEX; EXTRACELLULAR-MATRIX; MICRORNA
EXPRESSION; SYMPATHETIC NEURONS
AB Disrupted synchronized oscillatory firing of pyramidal neuronal networks in the cerebral cortex in the gamma frequency band (i.e., 30-100 Hz) mediates many of the cognitive deficits and symptoms of schizophrenia. In fact, the density of dendritic spines and the average somal area of pyramidal neurons in layer 3 of the cerebral cortex, which mediate both long-range (associational) and local (intrinsic) corticocortical connections, are decreased in subjects with this illness. To explore the molecular pathophysiology of pyramidal neuronal dysfunction, we extracted ribonucleic acid (RNA) from laser-captured pyramidal neurons from layer 3 of Brodmann's area 42 of the superior temporal gyrus (STG) from postmortem brains from schizophrenia and normal control subjects. We then profiled the messenger RNA (mRNA) expression of these neurons, using microarray technology. We identified 1331 mRNAs that were differentially expressed in schizophrenia, including genes that belong to the transforming growth factor beta (TGF-beta) and the bone morphogenetic proteins (BMPs) signaling pathways. Disturbances of these signaling mechanisms may in part contribute to the altered expression of other genes found to be differentially expressed in this study, such as those that regulate extracellular matrix (ECM), apoptosis, and cytoskeletal and synaptic plasticity. In addition, we identified 10 microRNAs (miRNAs) that were differentially expressed in schizophrenia; enrichment analysis of their predicted gene targets revealed signaling pathways and gene networks that were found by microarray to be dysregulated, raising an interesting possibility that dysfunction of pyramidal neurons in schizophrenia may in part be mediated by a concerted dysregulation of gene network functions as a result of the altered expression of a relatively small number of miRNAs. Taken together, findings of this study provide a neurobiological framework within which specific hypotheses about the molecular mechanisms of pyramidal cell dysfunction in schizophrenia can be formulated.
C1 [Pietersen, Charmaine Y.; Mauney, Sarah A.; Kim, Susie S.; Lim, Maribel P.; Woo, Tsung-Ung W.] McLean Hosp, Lab Cellular Neuropathol, Belmont, MA 02478 USA.
[Pietersen, Charmaine Y.; McCarley, Robert W.; Sonntag, Kai-C.; Woo, Tsung-Ung W.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Rooney, Robert J.] Genome Explorat Inc, Memphis, TN USA.
[Goldstein, Jill M.; Shenton, Martha E.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA.
[Petryshen, Tracey L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Seidman, Larry J.; McCarley, Robert W.; Woo, Tsung-Ung W.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA.
[McCarley, Robert W.] Vet Affairs Boston Healthcare Syst, Dept Psychiat, Brockton, MA USA.
[Sonntag, Kai-C.] McLean Hosp, Dept Psychiat, Belmont, MA 02478 USA.
RP Woo, TUW (reprint author), McLean Hosp, Mailman Res Ctr, Room 303E,115 Mill St, Belmont, MA 02478 USA.
EM wwoo@hms.harvard.edu
RI McCarley, Robert/N-5562-2014
OI McCarley, Robert/0000-0001-5705-7495
FU National Institutes of Health [P50MH080272, R01MH076060]
FX This study was supported by grants P50MH080272 (Boston CIDAR:
Vulnerability to Progression in Schizophrenia) and R01MH076060 from the
National Institutes of Health.
NR 111
TC 23
Z9 24
U1 1
U2 10
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 0167-7063
EI 1563-5260
J9 J NEUROGENET
JI J. Neurogenet.
PD MAR-JUN
PY 2014
VL 28
IS 1-2
SI SI
BP 53
EP 69
DI 10.3109/01677063.2014.882918
PG 17
WC Genetics & Heredity; Neurosciences
SC Genetics & Heredity; Neurosciences & Neurology
GA AH8SR
UT WOS:000336409000005
PM 24702465
ER
PT J
AU Pietersen, CY
Mauney, SA
Kim, SS
Passeri, E
Lim, MP
Rooney, RJ
Goldstein, JM
Petreyshen, TL
Seidman, LJ
Shenton, ME
Mccarley, RW
Sonntag, KC
Woo, TUW
AF Pietersen, Charmaine Y.
Mauney, Sarah A.
Kim, Susie S.
Passeri, Eleonora
Lim, Maribel P.
Rooney, Robert J.
Goldstein, Jill M.
Petreyshen, Tracey L.
Seidman, Larry J.
Shenton, Martha E.
Mccarley, Robert W.
Sonntag, Kai-C.
Woo, Tsung-Ung W.
TI Molecular Profiles of Parvalbumin-Immunoreactive Neurons in the Superior
Temporal Cortex in Schizophrenia
SO JOURNAL OF NEUROGENETICS
LA English
DT Article
DE cerebral cortex; gene expression profiling; laser capture
microdissection; microRNA
ID ADULT NERVOUS-SYSTEM; LASER-CAPTURE MICRODISSECTION; PREFRONTAL CORTEX;
SYNAPTIC PLASTICITY; BIPOLAR DISORDER; OXIDATIVE STRESS; EXPRESSION
PROFILES; MICRORNA EXPRESSION; GLUTATHIONE DEFICIT; NMDA RECEPTORS
AB Dysregulation of pyramidal cell network function by the soma- and axon-targeting inhibitory neurons that contain the calcium-binding protein parvalbumin (PV) represents a core pathophysiological feature of schizophrenia. In order to gain insight into the molecular basis of their functional impairment, we used laser capture microdissection (LCM) to isolate PV-immunolabeled neurons from layer 3 of Brodmann's area 42 of the superior temporal gyrus (STG) from postmortem schizophrenia and normal control brains. We then extracted ribonucleic acid (RNA) from these neurons and determined their messenger RNA (mRNA) expression profile using the Affymetrix platform of microarray technology. Seven hundred thirty-nine mRNA transcripts were found to be differentially expressed in PV neurons in subjects with schizophrenia, including genes associated with WNT (wingless-type), NOTCH, and PGE(2) (prostaglandin E-2) signaling, in addition to genes that regulate cell cycle and apoptosis. Of these 739 genes, only 89 (12%) were also differentially expressed in pyramidal neurons, as described in the accompanying paper, suggesting that the molecular pathophysiology of schizophrenia appears to be predominantly neuronal type specific. In addition, we identified 15 microRNAs (miRNAs) that were differentially expressed in schizophrenia; enrichment analysis of the predicted targets of these miRNAs included the signaling pathways found by microarray to be dysregulated in schizophrenia. Taken together, findings of this study provide a neurobiological framework within which hypotheses of the molecular mechanisms that underlie the dysfunction of PV neurons in schizophrenia can be generated and experimentally explored and, as such, may ultimately inform the conceptualization of rational targeted molecular intervention for this debilitating disorder.
C1 [Pietersen, Charmaine Y.; Mauney, Sarah A.; Kim, Susie S.; Passeri, Eleonora; Lim, Maribel P.; Woo, Tsung-Ung W.] McLean Hosp, Lab Cellular Neuropathol, Belmont, MA 02478 USA.
[Pietersen, Charmaine Y.; Passeri, Eleonora; Mccarley, Robert W.; Sonntag, Kai-C.; Woo, Tsung-Ung W.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Rooney, Robert J.] Genome Explorat Inc, Memphis, TN USA.
[Goldstein, Jill M.; Shenton, Martha E.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA.
[Petreyshen, Tracey L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Seidman, Larry J.; Mccarley, Robert W.; Woo, Tsung-Ung W.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA.
[Mccarley, Robert W.] Vet Affairs Boston Healthcare Syst, Dept Psychiat, Brockton, MA USA.
[Sonntag, Kai-C.] McLean Hosp, Dept Psychiat, Belmont, MA 02478 USA.
RP Woo, TUW (reprint author), McLean Hosp, Mailman Res Ctr, Room 303E,115 Mill St, Belmont, MA 02478 USA.
EM wwoo@hms.harvard.edu
RI McCarley, Robert/N-5562-2014
OI McCarley, Robert/0000-0001-5705-7495
FU National Institutes of Health [P50MH080272, R01MH076060]
FX This study was supported by grants P50MH080272 (Boston CIDAR:
Vulnerability to Progression in Schizophrenia) and R01MH076060 from the
National Institutes of Health.
NR 106
TC 17
Z9 17
U1 1
U2 11
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 0167-7063
EI 1563-5260
J9 J NEUROGENET
JI J. Neurogenet.
PD MAR-JUN
PY 2014
VL 28
IS 1-2
SI SI
BP 70
EP 85
DI 10.3109/01677063.2013.878339
PG 16
WC Genetics & Heredity; Neurosciences
SC Genetics & Heredity; Neurosciences & Neurology
GA AH8SR
UT WOS:000336409000006
PM 24628518
ER
PT J
AU Petrie, EC
Cross, DJ
Yarnykh, VL
Richards, T
Martin, NM
Pagulayan, K
Hoff, D
Hart, K
Mayer, C
Tarabochia, M
Raskind, MA
Minoshima, S
Peskind, ER
AF Petrie, Eric C.
Cross, Donna J.
Yarnykh, Vasily L.
Richards, Todd
Martin, Nathalie M.
Pagulayan, Kathleen
Hoff, David
Hart, Kim
Mayer, Cynthia
Tarabochia, Matthew
Raskind, Murray A.
Minoshima, Satoshi
Peskind, Elaine R.
TI Neuroimaging, Behavioral, and Psychological Sequelae of Repetitive
Combined Blast/ Impact Mild Traumatic Brain Injury in Iraq and
Afghanistan War Veterans
SO JOURNAL OF NEUROTRAUMA
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; WHITE-MATTER; AXONAL INJURY;
MULTIPLE-SCLEROSIS; DIFFUSION MRI; STEADY-STATE; HEAD-INJURY; FDG-PET;
IMAGES; ENCEPHALOPATHY
C1 [Petrie, Eric C.; Pagulayan, Kathleen; Hoff, David; Hart, Kim; Mayer, Cynthia; Tarabochia, Matthew; Raskind, Murray A.; Peskind, Elaine R.] VA Puget Sound, MIRECC, Vet Affairs VA Northwest Network VISN 20, Seattle, WA 98108 USA.
[Petrie, Eric C.; Pagulayan, Kathleen; Raskind, Murray A.; Peskind, Elaine R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Petrie, Eric C.; Cross, Donna J.; Yarnykh, Vasily L.; Richards, Todd; Martin, Nathalie M.; Minoshima, Satoshi] Univ Washington, Dept Radiol, Seattle, WA 98195 USA.
RP Petrie, EC (reprint author), VA Puget Sound, MIRECC, 1660 S Columbian Way,Mail Code S-116, Seattle, WA 98108 USA.
EM epetrie@uw.edu
RI Yarnykh, Vasily/G-8757-2016; Yarnykh, Vasiliy/N-7635-2014
OI Yarnykh, Vasily/0000-0002-1583-8979;
FU Department of Veterans Affairs Rehabilitation Research and Development
Service [B77421]; VA Clinical Science Research and Development CAREER
development award [TK2 CX000516]; VA Northwest Network MIRECC; National
Institute of Health [AG05136, 5K08AG23670, R21EB009908]
FX This material is based on work supported, in part, by the Department of
Veterans Affairs Rehabilitation Research and Development Service
(B77421), VA Clinical Science Research and Development CAREER
development award TK2 CX000516, and VA Northwest Network MIRECC;
National Institute of Health grants AG05136, 5K08AG23670, and
R21EB009908; and an anonymous foundation.
NR 71
TC 36
Z9 36
U1 5
U2 17
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
EI 1557-9042
J9 J NEUROTRAUM
JI J. Neurotrauma
PD MAR 1
PY 2014
VL 31
IS 5
BP 425
EP 436
DI 10.1089/NEU.2013.2952
PG 12
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA AB4ZV
UT WOS:000331799600241
PM 24102309
ER
PT J
AU Hook, GR
Yu, J
Sipes, N
Pierschbacher, MD
Hook, V
Kindy, MS
AF Hook, Gregory R.
Yu, Jin
Sipes, Nancy
Pierschbacher, Michael D.
Hook, Vivian
Kindy, Mark S.
TI The Cysteine Protease Cathepsin B Is a Key Drug Target and Cysteine
Protease Inhibitors Are Potential Therapeutics for Traumatic Brain
Injury
SO JOURNAL OF NEUROTRAUMA
LA English
DT Article
DE cathepsin B; cysteine protease inhibitor; motor function; traumatic
brain injury
ID CELL-FREE DNA; ALZHEIMERS-DISEASE; MITOCHONDRIAL-DNA; PREDICTIVE MARKER;
RAT-BRAIN; DAMAGE; REPAIR; NEUROTRAUMA; RADIATION; NUCLEAR
AB There are currently no effective therapeutic agents for traumatic brain injury (TBI), but drug treatments for TBI can be developed by validation of new drug targets and demonstration that compounds directed to such targets are efficacious in TBI animal models using a clinically relevant route of drug administration. The cysteine protease, cathepsin B, has been implicated in mediating TBI, but it has not been validated by gene knockout (KO) studies. Therefore, this investigation evaluated mice with deletion of the cathepsin B gene receiving controlled cortical impact TBI trauma. Results indicated that KO of the cathepsin B gene resulted in amelioration of TBI, shown by significant improvement in motor dysfunction, reduced brain lesion volume, greater neuronal density in brain, and lack of increased proapoptotic Bax levels. Notably, oral administration of the small-molecule cysteine protease inhibitor, E64d, immediately after TBI resulted in recovery of TBI-mediated motor dysfunction and reduced the increase in cathepsin B activity induced by TBI. E64d outcomes were as effective as cathepsin B gene deletion for improving TBI. E64d treatment was effective even when administered 8h after injury, indicating a clinically plausible time period for acute therapeutic intervention. These data demonstrate that a cysteine protease inhibitor can be orally efficacious in a TBI animal model when administered at a clinically relevant time point post-trauma, and that E64d-mediated improvement of TBI is primarily the result of inhibition of cathepsin B activity. These results validate cathepsin B as a new TBI therapeutic target.
C1 [Hook, Gregory R.; Sipes, Nancy; Pierschbacher, Michael D.] Amer Life Sci Pharmaceut, San Diego, CA USA.
[Yu, Jin; Kindy, Mark S.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
[Yu, Jin; Kindy, Mark S.] Appl Neurotechnol Inc, Charleston, SC USA.
[Hook, Vivian] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA.
[Kindy, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
RP Kindy, MS (reprint author), Med Univ S Carolina, Dept Neurosci, 173 Ashley Ave,BSB 403, Charleston, SC 29425 USA.
EM kindyms@musc.edu
FU NIH [R44AG032784, 5R01ES016774-02]; VA Merit Review [1I01RX000331-01]
FX The authors thank Christoph Peters, MD, of Albert Ludwig University
(Freiburg, Germany) for providing the cathepsin B-deficient mice and
Lawrence Marshall, MD, for reviewing the manuscript. This work was
supported, in part, by NIH grants R44AG032784 (to American Life Science
Pharmaceuticals; ALSP) and 5R01ES016774-02 (to M. S. K.) and VA Merit
Review 1I01RX000331-01 (to M.S.K.).
NR 31
TC 9
Z9 9
U1 0
U2 8
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
EI 1557-9042
J9 J NEUROTRAUM
JI J. Neurotrauma
PD MAR 1
PY 2014
VL 31
IS 5
BP 515
EP 529
DI 10.1089/NEU.2013.2944
PG 15
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA AB4ZV
UT WOS:000331799600250
PM 24083575
ER
PT J
AU Neuhaus, V
Bot, AGJ
Guitton, TG
Ring, DC
AF Neuhaus, Valentin
Bot, Arjan G. J.
Guitton, Thierry G.
Ring, David C.
TI Scapula Fractures: Interobserver Reliability of Classification and
Treatment
SO JOURNAL OF ORTHOPAEDIC TRAUMA
LA English
DT Article
DE OTA; AO fracture classification; New International Classification for
Scapular Fractures; reliability; scapula
ID DISPLACED CLAVICLE FRACTURES
AB Objectives:There is substantial variation in the classification and management of scapula fractures. The first purpose of this study was to analyze the interobserver reliability of the OTA/AO classification and the New International Classification for Scapula Fractures. The second purpose was to assess the proportion of agreement among orthopaedic surgeons on operative or nonoperative treatment.Design:Web-based reliability study.Setting:Independent orthopaedic surgeons from several countries were invited to classify scapular fractures in an online survey.Participants:One hundred three orthopaedic surgeons evaluated 35 movies of three-dimensional computerized tomography reconstruction of selected scapular fractures, representing a full spectrum of fracture patterns.Main Outcome Measurements:Fleiss kappa () was used to assess the reliability of agreement between the surgeons.Results:The overall agreement on the OTA/AO classification was moderate for the types (A, B, and C, = 0.54) with a 71% proportion of rater agreement (PA) and for the 9 groups (A1 to C3, = 0.47) with a 57% PA. For the New International Classification, the agreement about the intraarticular extension of the fracture (Fossa (F), = 0.79) was substantial and the agreement about a fractured body (Body (B), = 0.57) or process was moderate (Process (P), = 0.53); however, PAs were more than 81%. The agreement on the treatment recommendation was moderate ( = 0.57) with a 73% PA.Conclusions:The New International Classification was more reliable. Body and process fractures generated more disagreement than intraarticular fractures and need further clear definitions.
C1 [Neuhaus, Valentin; Bot, Arjan G. J.; Guitton, Thierry G.; Ring, David C.] Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA.
RP Ring, DC (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA.
EM dring@partners.org
RI Fernandes, C/F-9839-2012;
OI adolfsson, lars/0000-0001-7873-3093; Neuhaus,
Valentin/0000-0003-4012-5628; Fernandes, C/0000-0003-0146-6091; Guitton,
Thierry/0000-0002-2599-1985; Gummerson, Nigel/0000-0002-5727-8041;
Streubel, Philipp/0000-0002-4585-1779
FU Bangerter Foundation Switzerland; VSB fonds; Beurs Prins Bernhard
Cultuur fonds; beurs/Banning-de Jong fonds; Stichting Anna fonds, the
Netherlands
FX V. Neuhaus has received a grant from the Bangerter Foundation
Switzerland. A. G. J. Bot has received grants from VSB fonds, Beurs
Prins Bernhard Cultuur fonds, beurs/Banning-de Jong fonds, Stichting
Anna fonds, the Netherlands. T. G. Guitton had no conflicts of interest.
D. C. Ring has no conflicts related to this research.
NR 20
TC 6
Z9 6
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0890-5339
EI 1531-2291
J9 J ORTHOP TRAUMA
JI J. Orthop. Trauma
PD MAR
PY 2014
VL 28
IS 3
BP 124
EP 129
DI 10.1097/BOT.0b013e31829673e2
PG 6
WC Orthopedics; Sport Sciences
SC Orthopedics; Sport Sciences
GA AG3MZ
UT WOS:000335324900006
PM 23629469
ER
PT J
AU Grigoryan, KV
Javedan, H
Rudolph, JL
AF Grigoryan, Konstantin V.
Javedan, Houman
Rudolph, James L.
TI Orthogeriatric Care Models and Outcomes in Hip Fracture Patients: A
Systematic Review and Meta-Analysis
SO JOURNAL OF ORTHOPAEDIC TRAUMA
LA English
DT Review
DE hip fracture; geriatrics; orthopaedic surgery; aged; mortality;
meta-analysis
ID RANDOMIZED CONTROLLED-TRIAL; OLDER-ADULTS; GERIATRIC CONSULTATION;
INTERVENTION; MANAGEMENT; MORTALITY; DELIRIUM; STANDARD; RECOVERY;
PROGRAM
AB Objectives:Hip fractures are common, morbid, and costly health events that threaten independence and function of older patients. The purpose of this systematic review and meta-analysis was to determine if orthogeriatric collaboration models improve outcomes.Data sources:Articles in English and Spanish languages were searched in the electronic databases including MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, and the Cochrane Registry from 1992 to 2012.Study selection:Studies were included if they described an inpatient multidisciplinary approach to hip fracture management involving an orthopaedic surgeon and a geriatrician. Studies were grouped into 3 following categories: routine geriatric consultation, geriatric ward with orthopaedic consultation, and shared care. After independent review of 1480 citations by 2 authors, 18 studies (9094 patients) were identified as meeting the inclusion criteria.Data extraction:In-hospital mortality, length of stay, and long-term mortality outcomes were collected.Data synthesis:A random effects model meta-analysis determined whether orthogeriatric collaboration was associated with improved outcomes. The overall meta-analysis found that orthogeriatric collaboration was associated with a significant reduction of in-hospital mortality [relative risk 0.60; 95% confidence interval (95% CI), 0.43-0.84) and long-term mortality (relative risk 0.83; 95% CI, 0.74-0.94). Length of stay (standardized mean difference -0.25; 95% CI, -0.44 to -0.05) was significantly reduced, particularly in the shared care model (standardized mean difference -0.61; 95% CI, -0.95 to -0.28), but heterogeneity limited this interpretation. Other variables such as time to surgery, delirium, and functional status were measured infrequently.Conclusions:This meta-analysis supports orthogeriatric collaboration to improve mortality after hip repair. Further study is needed to determine the best model of orthogeriatric collaboration and if these partnerships improve functional outcomes.
C1 [Grigoryan, Konstantin V.] Univ Cincinnati, Coll Med, Cincinnati, OH USA.
[Javedan, Houman; Rudolph, James L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA.
[Rudolph, James L.] VA Boston Healthcare Syst, GRECC, Boston, MA 02130 USA.
RP Rudolph, JL (reprint author), VA Boston Healthcare Syst, GRECC, 150 S Huntington Ave, Boston, MA 02130 USA.
EM jrudolph@partners.org
FU NIH [1T35AG038027-02]; VA Rehabilitation Research and Development Career
Development Award
FX Support for this research was made possible through NIH grant #:
1T35AG038027-02. Dr J. L. Rudolph is supported by a VA Rehabilitation
Research and Development Career Development Award.
NR 33
TC 52
Z9 53
U1 5
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0890-5339
EI 1531-2291
J9 J ORTHOP TRAUMA
JI J. Orthop. Trauma
PD MAR
PY 2014
VL 28
IS 3
BP E49
EP E55
DI 10.1097/BOT.0b013e3182a5a045
PG 7
WC Orthopedics; Sport Sciences
SC Orthopedics; Sport Sciences
GA AG3MZ
UT WOS:000335324900002
PM 23912859
ER
PT J
AU Janne, PA
Cohen, RB
Laird, AD
Mace, S
Engelman, JA
Ruiz-Soto, R
Rockich, K
Xu, JB
Shapiro, GI
Martinez, P
Felip, E
AF Jaenne, Pasi A.
Cohen, Roger B.
Laird, A. Douglas
Mace, Sandrine
Engelman, Jeffrey A.
Ruiz-Soto, Rodrigo
Rockich, Kevin
Xu, Jianbo
Shapiro, Geoffrey I.
Martinez, Pablo
Felip, Enriqueta
TI Phase I Safety and Pharmacokinetic Study of the PI3K/mTOR Inhibitor
SAR245409 ( XL765) in Combination with Erlotinib in Patients with
Advanced Solid Tumors
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Article
DE PI3K; mammalian target of rapamycin inhibitor; Epidermal growth factor
receptor inhibitor; Pharmacokinetics; Pharmacodynamics; Advanced solid
tumors
ID PHOSPHOINOSITIDE 3-KINASE PATHWAY; PI3K INHIBITION; LUNG-CANCER;
RESISTANCE; EGFR; GEFITINIB; GROWTH; KINASE; CELLS
AB Introduction: The primary objectives of this phase I study were to evaluate the safety and maximum tolerated dose (MTD) of SAR245409, a pan-class I phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin inhibitor, combined with erlotinib in patients with advanced solid tumors.
Methods: Forty-six patients with advanced solid tumors were enrolled. Patients with lung cancer (n = 37) had received an epidermal growth factor receptor (EGFR) inhibitor before study entry. SAR245409 30, 50, 70, or 90 mg once daily (QD) or 20 or 30 mg twice daily (BID) was administered, in combination with erlotinib 100 mg QD, in 28-day cycles. Dose escalation of SAR245409 followed a standard 3 + 3 design. Patients were evaluated for adverse events (AEs). Additional evaluations included pharmacokinetics, pharmacodynamic effects on PI3K and EGFR/mitogen-activated protein kinase signaling pathways in tumor and skin samples, and tumor response.
Results: The MTDs of SAR245409, in combination with erlotinib 100 mg QD, were 70 mg QD and 20 mg BID. The most frequently reported treatment-related AEs (any grade) were diarrhea (35%), rash (35%), and nausea (28%). No treatment-related AE occurred at grade 3/4 in more than one patient (2.2%). No major pharmacokinetic interaction between SAR245409 and erlotinib was noted. Suppression of PI3K and EGFR/mitogen-activated protein kinase signaling pathway biomarkers was observed in skin and tumor samples. Stable disease was the best overall response reported, occurring in 12 of 32 (37.5%) evaluable patients.
Conclusion: MTDs of SAR245409 and erlotinib were below the single-agent doses of either agent, despite the lack of major pharmacokinetic interaction.
C1 [Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02215 USA.
[Jaenne, Pasi A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02215 USA.
[Cohen, Roger B.] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA.
[Laird, A. Douglas] Exelixis Inc, Translat Med, San Francisco, CA USA.
[Mace, Sandrine] Sanofi, Translat & Expt Med, Vitry Sur Seine, France.
[Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Ctr Thorac Ctr, Charlestown, MA USA.
[Ruiz-Soto, Rodrigo] Sanofi, Clin Dev Oncol, Cambridge, MA USA.
[Rockich, Kevin] Sanofi, Pharmacokinet Modeling & Simulat, Cambridge, MA USA.
[Xu, Jianbo] Sanofi, Biostat & Programming, Cambridge, MA USA.
[Shapiro, Geoffrey I.] Dana Farber Canc Inst, Early Drug Dev Ctr, Boston, MA 02115 USA.
[Martinez, Pablo; Felip, Enriqueta] Vall Debron Univ Hosp, Dept Med Oncol, Barcelona, Spain.
RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 450 Brookline Ave,HIM223, Boston, MA 02215 USA.
EM Pasi_Janne@dfci.harvard.edu
FU Sanofi
FX The authors thank participating patients and their families as well as
Art DeCillis (VP Medical Affairs and Clinical Research, Exelixis) and
the clinical research team at Exelixis who initiated this trial. In
addition, the authors thank Bin Wu (Sanofi), Linh Nguyen, Frauke
Bentzien, Belinda Cancilla, and Valentina Vysotskaia (Exelixis) for
their contributions to PK, pharmacodynamic, and molecular profiling
analyses and Coumaran Egile (Sanofi) for his contribution to this work.
This study was funded by Sanofi. Editorial assistance in the form of
medical writing services was provided by Melissa Purves and Simone Blagg
of MediTech Media, funded by Sanofi.
NR 23
TC 14
Z9 15
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD MAR
PY 2014
VL 9
IS 3
BP 316
EP 323
DI 10.1097/JTO.0000000000000088
PG 8
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA AB1EO
UT WOS:000331534500011
PM 24496004
ER
PT J
AU Lehavot, K
Katon, JG
Williams, EC
Nelson, KM
Gardella, CM
Reiber, GE
Simpson, TL
AF Lehavot, Keren
Katon, Jodie G.
Williams, Emily C.
Nelson, Karin M.
Gardella, Carolyn M.
Reiber, Gayle E.
Simpson, Tracy L.
TI Sexual Behaviors and Sexually Transmitted Infections in a Nationally
Representative Sample of Women Veterans and Nonveterans
SO JOURNAL OF WOMENS HEALTH
LA English
DT Article
ID HUMAN-PAPILLOMAVIRUS INFECTION; SIMPLEX-VIRUS TYPE-2; UNITED-STATES;
HEALTH-CARE; CHLAMYDIAL INFECTION; MINORITY VETERANS; RISK BEHAVIOR; US
MILITARY; CONDOM USE; GONORRHEA
AB Background: Women veterans are a growing population with unique characteristics and documented health disparities. Few studies have examined their sexual behaviors and rates of sexually transmitted infections (STIs), and none have compared women veterans to nonveterans to identify potential sexual health disparities. Methods: We used data from the 1999-2010 National Health and Nutrition Examination Survey, a nationally representative U.S. survey. We compared lifetime sexual history (age at first intercourse, number of partners), sexual activity in the last year, and STIs between women veterans (n=151) and nonveterans (n=8738), adjusting for age, race/ethnicity, education, marital status, binge drinking, and survey year. Results: Compared to nonveterans, women veterans reported a younger age at first intercourse and a greater number of female and male lifetime sexual partners, and they were more likely to have ever had sex with a woman. They were also more likely than nonveterans to have genital herpes and genital warts. Conclusions: Women veterans reported higher rates of sexual activity and STIs than nonveterans. Future research is needed to assess high-risk behaviors and determine what factors may underlie these associations. Providers should ensure thorough screening and intervention services are provided for this growing population.
C1 [Lehavot, Keren; Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA.
[Lehavot, Keren; Simpson, Tracy L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Katon, Jodie G.; Williams, Emily C.; Nelson, Karin M.; Reiber, Gayle E.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev HSR&D, Seattle, WA 98108 USA.
[Katon, Jodie G.] Dept Vet Affairs, VA Off Womens Hlth Serv, Washington, DC USA.
[Katon, Jodie G.; Williams, Emily C.; Reiber, Gayle E.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Nelson, Karin M.] Univ Washington, Dept Med, Seattle, WA USA.
[Gardella, Carolyn M.] VA Puget Sound Hlth Care Syst, Gynecol Serv, Seattle, WA 98108 USA.
[Gardella, Carolyn M.] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA.
[Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98108 USA.
RP Lehavot, K (reprint author), VA Puget Sound Hlth Care Syst, MIRECC, 1660 S Columbian Way S-116 POC, Seattle, WA 98108 USA.
EM klehavot@uw.edu
FU Associated Health Postdoctoral Fellowship [TPP 61-026]; Career
Development Award [CDA 12-276]; Senior Career Scientist Award grant [RCS
98-353]; National Institute of Mental Health [R25 MH080916-01A2];
Department of Veterans Affairs, Health Services Research & Development
Service, Quality Enhancement Research Initiative (QUERI)
FX This material is the result of work supported by resources from the U.S.
Department of Veterans Affairs Office of Academic Affiliations, Advanced
Fellowship Program in Mental Illness Research and Treatment (K.L.),
Associated Health Postdoctoral Fellowship (J.K., no. TPP 61-026), Career
Development Award (E.W., CDA 12-276), Senior Career Scientist Award
grant (G.R., no. RCS 98-353), and the VA Puget Sound Health Care System,
Seattle, Washington. EW is an investigator with the Implementation
Research Institute (IRI) at the George Warren Brown School of Social
Work at Washington University in St. Louis. IRI is supported through an
award from the National Institute of Mental Health (R25 MH080916-01A2)
and the Department of Veterans Affairs, Health Services Research &
Development Service, Quality Enhancement Research Initiative (QUERI).
The authors would like to thank Jeff Rodenbaugh for managing the data.
The views expressed in this article are those of the authors and do not
represent the views of the Department of Veterans Affairs or the United
States government.
NR 47
TC 7
Z9 7
U1 1
U2 6
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
EI 1931-843X
J9 J WOMENS HEALTH
JI J. Womens Health
PD MAR 1
PY 2014
VL 23
IS 3
BP 246
EP 252
DI 10.1089/jwh.2013.4327
PG 7
WC Public, Environmental & Occupational Health; Medicine, General &
Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
Medicine; Obstetrics & Gynecology; Women's Studies
GA AC4BQ
UT WOS:000332466000010
PM 24328438
ER
PT J
AU Whiteman, KR
Johnson, HA
Mayo, MF
Audette, CA
Carrigan, CN
LaBelle, A
Zukerberg, L
Lambert, JM
Lutz, RJ
AF Whiteman, Kathleen R.
Johnson, Holly A.
Mayo, Michele F.
Audette, Charlene A.
Carrigan, Christina N.
LaBelle, Alyssa
Zukerberg, Lawrence
Lambert, John M.
Lutz, Robert J.
TI Lorvotuzumab mertansine, a CD56-targeting antibody-drug conjugate with
potent antitumor activity against small cell lung cancer in human
xenograft models
SO MABS
LA English
DT Article
DE small cell lung cancer; CD56; antibody-drug conjugate; ADC;
maytansinoid; combination therapy; xenografts
ID ADHESION MOLECULES; ANTICANCER DRUGS; IN-VITRO; CISPLATIN; EXPRESSION;
CARCINOMA; ETOPOSIDE; PACLITAXEL; NCAM; IMMUNOCONJUGATE
AB Lorvotuzumab mertansine (LM) is an antibody-drug conjugate composed of a humanized anti-CD56 antibody, lorvotuzumab, linked via a cleavable disulfide linker to the tubulin-binding maytansinoid DM1. CD56 is expressed on most small cell lung cancers (SCLC), providing a promising therapeutic target for treatment of this aggressive cancer, which has a poor five-year survival rate of only 5-10%. We performed immunohistochemical staining on SCLC tumor microarrays, which confirmed that CD56 is expressed at high levels on most (similar to 74%) SCLC tumors. Conjugation of lorvotuzumab with DM1 did not alter its specific binding to cells and LM demonstrated potent target-dependent cytotoxicity against CD56-positive SCLC cells in vitro. The anti-tumor activity of LM was evaluated against SCLC xenograft models in mice, both as monotherapy and in combination with platinum/etoposide and paclitaxel/carboplatin. Dose-dependent and antigen-specific anti-tumor activity of LM monotherapy was demonstrated at doses as low as 3 mg/kg. LM was highly active in combination with standard-of-care platinum/etoposide therapies, even in relatively resistant xenograft models. LM demonstrated outstanding anti-tumor activity in combination with carboplatin/etoposide, with superior activity over chemotherapy alone when LM was used in combinations at significantly reduced doses (6-fold below the minimally efficacious dose for LM monotherapy). The combination of LM with carboplatin/paclitaxel was also highly active. This study provides the rationale for clinical evaluation of LM as a promising novel targeted therapy for SCLC, both as monotherapy and in combination with chemotherapy.
C1 [Whiteman, Kathleen R.; Johnson, Holly A.; Mayo, Michele F.; Audette, Charlene A.; Carrigan, Christina N.; LaBelle, Alyssa; Lambert, John M.; Lutz, Robert J.] ImmunoGen Inc, Waltham, MA 02451 USA.
[Zukerberg, Lawrence] Harvard Univ, Sch Med, Boston, MA USA.
[Zukerberg, Lawrence] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Whiteman, KR (reprint author), ImmunoGen Inc, Waltham, MA 02451 USA.
EM kathleen.whiteman@immunogen.com
NR 47
TC 17
Z9 17
U1 0
U2 17
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1942-0862
EI 1942-0870
J9 MABS-AUSTIN
JI mAbs
PD MAR-APR
PY 2014
VL 6
IS 2
BP 556
EP 566
DI 10.4161/mabs.27756
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AH6HL
UT WOS:000336231200022
PM 24492307
ER
PT J
AU Ploumis, A
Christodoulou, P
Wood, KB
Varvarousis, D
Sarni, JL
Beris, A
AF Ploumis, Avraam
Christodoulou, Pavlos
Wood, Kirkham B.
Varvarousis, Dimitrios
Sarni, James L.
Beris, Alexander
TI Original Research Article Caudal vs Transforaminal Epidural Steroid
Injections as Short-Term ( 6 Months) Pain Relief in Lumbar Spinal
Stenosis Patients with Sciatica
SO PAIN MEDICINE
LA English
DT Article
DE Injections; Transforaminal; Caudal; Stenosis
ID MEDICINE PRACTICE GUIDELINES; RADICULAR PAIN; EFFICACY; BLIND;
MANAGEMENT; HERNIATION
AB ObjectiveThe aim of this study is to evaluate prospectively the efficacy of caudal epidural steroid injection (CESI) and transforaminal epidural steroid injection (TFESI) in lumbar spinal stenosis patients with sciatic pain.
DesignProspective clinical study.
Setting and PatientsThirty-one patients (average age 62 years) from two hospitals, with single dermotomal distribution of sciatic pain due to spinal stenosis were included in the study.
InterventionsPatients underwent epidural steroid injections done by the same injectionist. Eleven patients from one hospital were included in the CESI group, while the TFESI group consisted of 20 comparable patients from the second site.
Outcome MeasuresPrimary outcome measure was the complete relief or at least 50% reduction of pain (visual analog scale [VAS]) at 6 months postinjection. Secondary outcome measures were the improvement of function (of at least 15 points of Oswestry Disability Index [ODI]) at 6 months and the changes of VAS and ODI and at 2 weeks, at 3 months, and at 6 months postinjection.
ResultsA significantly greater number of stenosis patients showed pain relief at 6 months postinjection with TFSI (90%) than with CESI (54.54%). All patients with TFSI showed improvement of function at 6 months while only three (27.27%) patients with caudal epidural improved functionally. Out of the total 31 patients, two patients from group A underwent a second CESI at 15 days postinjection and decompressive spine surgery between 3 and 6 months postinjection.
ConclusionsThe effectiveness of transforaminal steroid injection for the stenosis patients with sciatica was superior to caudal at 6 months postinjection.
C1 [Ploumis, Avraam; Varvarousis, Dimitrios; Beris, Alexander] Univ Hosp Ioannina, Dept Orthopaed Surg, Ioannina, Greece.
[Ploumis, Avraam; Varvarousis, Dimitrios; Beris, Alexander] Univ Hosp Ioannina, Dept Rehabil, Ioannina, Greece.
[Ploumis, Avraam; Christodoulou, Pavlos] 424 Gen Army Hosp, Dept Orthopaed, Thessaloniki, Greece.
[Ploumis, Avraam; Wood, Kirkham B.; Sarni, James L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed, Boston, MA USA.
RP Ploumis, A (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey 3-3a, Boston, MA 02114 USA.
EM aploumis@cc.uoi.gr
NR 22
TC 8
Z9 8
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1526-2375
EI 1526-4637
J9 PAIN MED
JI Pain Med.
PD MAR
PY 2014
VL 15
IS 3
BP 379
EP 385
DI 10.1111/pme.12318
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA AC2GU
UT WOS:000332318600005
PM 24341966
ER
PT J
AU Frank, JW
Bair, MJ
Becker, WC
Krebs, EE
Liebschutz, JM
Alford, DP
AF Frank, Joseph W.
Bair, Matthew J.
Becker, William C.
Krebs, Erin E.
Liebschutz, Jane M.
Alford, Daniel P.
TI Update in Pain Medicine for Primary Care Providers: A Narrative Review,
2010-2012
SO PAIN MEDICINE
LA English
DT Review
DE Pain Management; Primary Care; Interventional; Opioids; Neuropathic
Pain; Exercise; Psychotherapy; Physical Therapy
ID LOW-BACK-PAIN; RANDOMIZED CONTROLLED-TRIAL; NEUROPATHIC PAIN; STEPPED
CARE; MANAGEMENT; YOGA; INTERVENTIONS; METAANALYSIS; POPULATION;
PREVALENCE
AB ObjectiveThis manuscript reviews peer-reviewed literature published from 2010-2012 relevant to the management of chronic pain in the primary care setting.
DesignNarrative review of peer-reviewed literature.
MethodsWe searched MEDLINE, PubMed, and reference lists and queried expert contacts for English-language studies related to the management of chronic noncancer pain in adult patients in primary care settings. One investigator reviewed all eligible studies for relevance, and 47 studies were reviewed by all authors and rated according to their impact on 1) primary care clinical practice, 2) policy, 3) research, and 4) quality of study methods. Through iterative discussion, nine articles were selected for detailed review and discussion.
ResultsWe present articles in six topic areas: interventional pain management; opioid dose and risk of overdose death; neuropathic pain; yoga for chronic low back pain; cognitive behavioral therapy; and systematic approaches to treating back pain. We discuss implications for pain management in primary care.
ConclusionsThere is growing evidence for the risks, benefits, and limitations of the multiple modalities available to primary care providers for the management of chronic pain. The dissemination and implementation of the evidence from these studies as well as novel system-level interventions warrant additional study and support from clinicians, educators, and policy makers.
C1 [Frank, Joseph W.] Univ Colorado, Sch Med, Div Gen Internal Med, Denver VA Med Ctr, Aurora, CO 80045 USA.
[Bair, Matthew J.] Indiana Univ, Sch Med, Roudebush VA Med Ctr, Indianapolis, IN USA.
[Becker, William C.] Yale Univ, Sch Med, VA Connecticut Healthcare Syst, New Haven, CT USA.
[Krebs, Erin E.] Univ Minnesota, Sch Med, Minneapolis VA Med Ctr, Minneapolis, MN 55455 USA.
[Liebschutz, Jane M.; Alford, Daniel P.] Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02118 USA.
[Liebschutz, Jane M.] Boston Univ, Sch Publ Hlth, Boston, MA USA.
RP Frank, JW (reprint author), Univ Colorado, Sch Med, Div Gen Internal Med, 8th Floor,Acad Off 1,Mailstop B180, Aurora, CO 80045 USA.
EM joseph.frank@ucdenver.edu
FU an institutional National Research Service Award [T32HP10251]; VA HSR&D
Research Career Development Awards
FX All authors are members of the Society of General Internal Medicine's
Pain Medicine Interest Group. This article derives from the presentation
"Update in Pain Medicine" at the 36th annual meeting of SGIM in April
2013 in Denver, Colorado. Dr. Frank was supported by an institutional
National Research Service Award (T32HP10251). Drs. Becker and Krebs are
supported by VA HSR&D Research Career Development Awards.
NR 34
TC 3
Z9 3
U1 2
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1526-2375
EI 1526-4637
J9 PAIN MED
JI Pain Med.
PD MAR
PY 2014
VL 15
IS 3
BP 425
EP 431
DI 10.1111/pme.12337
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA AC2GU
UT WOS:000332318600010
PM 24423083
ER
PT J
AU Giblin, K
Newmark, JL
Brenner, GJ
Wainger, BJ
AF Giblin, Kathryn
Newmark, Jordan L.
Brenner, Gary J.
Wainger, Brian J.
TI Headache Plus: Trigeminal and Autonomic Features in a Case of
Cervicogenic Headache Responsive to Third Occipital Nerve Radiofrequency
Ablation
SO PAIN MEDICINE
LA English
DT Article
DE Cervicogenic Headache; Trigeminal Autonomic Cephalgia; Radiofrequency
Ablation; Third Occipital Nerve
ID ZYGAPOPHYSEAL-JOINT PAIN; HEMICRANIA CONTINUA; CLUSTER HEADACHE;
DIAGNOSTIC-CRITERIA; DOUBLE-BLIND; ATTACKS; ACTIVATION; INJECTION;
NEUROTOMY
AB ObjectiveTo describe a case of cervicogenic headache with associated autonomic features and pain in a trigeminal distribution, all of which responded to third occipital nerve radiofrequency ablation.
DesignSingle case report.
SettingMassachusetts General Hospital Center for Pain Medicine.
PatientsA 38-year-old woman with history of migraines and motor vehicle accident.
InterventionsRight third occipital nerve diagnostic blocks and radiofrequency lesioning.
Outcome MeasuresPain reduction; physical findings, including periorbital and mandibular facial swelling, tearing, conjunctival injection, and allodynia; and use of opioid and non-opioid pain medicines.
ResultsThe patient had complete relief of her pain and autonomic symptoms, and was able to stop all pain medications following a dedicated third occipital nerve lesioning.
ConclusionsThis case illustrates the diagnostic and therapeutic complexity of cervicogenic headache and the overlap with other headache types, including trigeminal autonomic cephalgias and migraine. It represents a unique proof of principle in that not only trigeminal nerve pain but also presumed neurogenic inflammation can be relieved by blockade of cervical nociceptive inputs. Further investigation into shared mechanisms of headache pathogenesis is warranted.
C1 [Giblin, Kathryn; Newmark, Jordan L.; Brenner, Gary J.; Wainger, Brian J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Brenner, GJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, WACC 340, Boston, MA 02114 USA.
EM gjbrenner@partners.org
NR 33
TC 2
Z9 2
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1526-2375
EI 1526-4637
J9 PAIN MED
JI Pain Med.
PD MAR
PY 2014
VL 15
IS 3
BP 473
EP 478
DI 10.1111/pme.12334
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA AC2GU
UT WOS:000332318600016
PM 24401103
ER
PT J
AU Hagen, CE
Lauwers, GY
Mino-Kenudson, M
AF Hagen, Catherine E.
Lauwers, Gregory Y.
Mino-Kenudson, Mari
TI Barrett esophagus: Diagnostic challenges
SO SEMINARS IN DIAGNOSTIC PATHOLOGY
LA English
DT Article
DE Esophageal adenocarcinoma; Intestinal metaplasia; Crypt dysplasia;
Foveolar dysplasia; Carditis
ID ENDOSCOPIC MUCOSAL RESECTION; LOW-GRADE DYSPLASIA; P53 PROTEIN
EXPRESSION; INTESTINAL METAPLASIA; GASTROESOPHAGEAL JUNCTION; DISTAL
ESOPHAGUS; MULTILAYERED EPITHELIUM; NEOPLASTIC PROGRESSION; COLUMNAR
EPITHELIUM; DISEASE PROGRESSION
AB The incidence of esophageal adenocarcinoma and associated mortality has risen dramatically over the past several decades, and, thus, it is increasingly important to understand its pathogenesis and risk factors. Barrett esophagus is the established precursor to esophageal adenocarcinoma that progresses through a metaplasia-dysplasia-carcinoma sequence. Its risk of transforming to carcinoma is not as high as previously reported and there appears to be a biological heterogeneity among patients with this disease. The overall prevalence of Barrett esophagus in the United States ranges from 1% to 25% and is closer to 5% in patients with gastroesophageal reflux disease. Because of the frequency of Barrett esophagus and associated implications, it is important for the practicing pathologist to have a thorough understanding of this disease and its diagnostic pitfalls. In this review, we will discuss issues associated with the diagnosis of Barrett esophagus, including the definition of Barrett esophagus and its distinction from carditis with intestinal metaplasia. We will also discuss challenges in the grading of dysplasia and new variants of dysplasia, including crypt dysplasia and foveolar-type dysplasia. Finally, we will touch upon the evaluation of dysplasia in endoscopic mucosal resection specimens. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Hagen, Catherine E.; Lauwers, Gregory Y.; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Hagen, Catherine E.; Lauwers, Gregory Y.; Mino-Kenudson, Mari] Harvard Univ, Sch Med, Boston, MA USA.
RP Mino-Kenudson, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 122, Boston, MA 02114 USA.
EM mminokenudson@partners.org
OI Hagen, Catherine/0000-0002-1867-4957
NR 76
TC 2
Z9 3
U1 0
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 0740-2570
EI 1930-1111
J9 SEMIN DIAGN PATHOL
JI Semin. Diagn. Pathol.
PD MAR
PY 2014
VL 31
IS 2
BP 100
EP 113
DI 10.1053/j.semdp.2014.02.005
PG 14
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA AH9MR
UT WOS:000336467000002
PM 24815936
ER
PT J
AU Baltarowich, OH
Di Salvo, DN
Scoutt, LM
Brown, DL
Cox, CW
DiPietro, MA
Glazer, DI
Hamper, UM
Manning, MA
Nazarian, LN
Neutze, JA
Romero, M
Stephenson, JW
Dubinsky, TJ
AF Baltarowich, Oksana H.
Di Salvo, Donald N.
Scoutt, Leslie M.
Brown, Douglas L.
Cox, Christian W.
DiPietro, Michael A.
Glazer, Daniel I.
Hamper, Ulrike M.
Manning, Maria A.
Nazarian, Levon N.
Neutze, Janet A.
Romero, Miriam
Stephenson, Jason W.
Dubinsky, Theodore J.
TI National Ultrasound Curriculum for Medical Students
SO ULTRASOUND QUARTERLY
LA English
DT Article
DE ultrasound; curriculum; medical student; medical student education;
medical school curriculum; diagnostic ultrasound
ID SONOGRAPHY
AB Ultrasound (US) is an extremely useful diagnostic imaging modality because of its real-time capability, noninvasiveness, portability, and relatively low cost. It carries none of the potential risks of ionizing radiation exposure or intravenous contrast administration. For these reasons, numerous medical specialties now rely on US not only for diagnosis and guidance for procedures, but also as an extension of the physical examination. In addition, many medical school educators recognize the usefulness of this technique as an aid to teaching anatomy, physiology, pathology, and physical diagnosis. Radiologists are especially interested in teaching medical students the appropriate use of US in clinical practice. Educators who recognize the power of this tool have sought to incorporate it into the medical school curriculum. The basic question that educators should ask themselves is: What should a student graduating from medical school know about US? To aid them in answering this question, US specialists from the Society of Radiologists in Ultrasound and the Alliance of Medical School Educators in Radiology have collaborated in the design of a US curriculum for medical students. The implementation of such a curriculum will vary from institution to institution, depending on the resources of the medical school and space in the overall curriculum. Two different examples of how US can be incorporated vertically or horizontally into a curriculum are described, along with an explanation as to how this curriculum satisfies the Accreditation Council for Graduate Medical Education competencies, modified for the education of our future physicians.
C1 [Baltarowich, Oksana H.; Nazarian, Levon N.] Jefferson Ultrasound Radiol & Educ Inst, Dept Radiol, Philadelphia, PA USA.
[Baltarowich, Oksana H.; Nazarian, Levon N.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
[Di Salvo, Donald N.] Harvard Univ, Sch Med, Boston, MA USA.
[Di Salvo, Donald N.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Scoutt, Leslie M.] Yale Univ, Sch Med, Dept Diagnost Radiol, New Haven, CT 06510 USA.
[Brown, Douglas L.] Mayo Clin, Coll Med, Rochester, MN USA.
[Brown, Douglas L.] Mayo Clin, Rochester, MN USA.
[Cox, Christian W.] Univ Colorado, Sch Med, Rocky Vista Univ, Coll Osteopath Med, Denver, CO USA.
[Cox, Christian W.] Natl Jewish Hlth, Denver, CO USA.
[DiPietro, Michael A.] CS Mott Childrens Hosp, Ann Arbor, MI USA.
[DiPietro, Michael A.; Glazer, Daniel I.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Hamper, Ulrike M.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21218 USA.
[Manning, Maria A.] Univ Maryland, Sch Med, Dept Radiol, Baltimore, MD 21201 USA.
[Nazarian, Levon N.] Thomas Jefferson Univ, Dept Radiol, Philadelphia, PA 19107 USA.
[Neutze, Janet A.] Penn State Hershey Med Ctr, Hershey, PA USA.
[Romero, Miriam] Univ So Calif, Keck Sch Med, Dept Radiol, Los Angeles, CA 90033 USA.
[Stephenson, Jason W.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Radiol, Madison, WI USA.
[Dubinsky, Theodore J.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA.
RP Baltarowich, OH (reprint author), Thomas Jefferson Univ, Dept Radiol, Jefferson Ultrasound Radiol & Educ Inst, 132 S 10th St,Suite 763D, Philadelphia, PA 19107 USA.
EM oksana.baltarowich@jefferson.edu
RI Neutze, Janet/B-6123-2015
OI Neutze, Janet/0000-0001-5870-8798
NR 17
TC 16
Z9 17
U1 1
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0894-8771
EI 1536-0253
J9 ULTRASOUND Q
JI Ultrasound Q.
PD MAR
PY 2014
VL 30
IS 1
BP 13
EP 19
DI 10.1097/RUQ.0000000000000066
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AH2UZ
UT WOS:000335978500004
PM 24901774
ER
PT J
AU Lalwani, N
Dubinsky, T
Javitt, MC
Gaffney, DK
Glanc, P
Elshaikh, MA
Kim, YB
Lee, LJ
Pannu, HK
Royal, HD
Shipp, TD
Siegel, CL
Simpson, L
Wahl, AO
Wolfson, AH
Zelop, CM
AF Lalwani, Neeraj
Dubinsky, Theodore
Javitt, Marcia C.
Gaffney, David K.
Glanc, Phyllis
Elshaikh, Mohamed A.
Kim, Young Bae
Lee, Larissa J.
Pannu, Harpreet K.
Royal, Henry D.
Shipp, Thomas D.
Siegel, Cary Lynn
Simpson, Lynn
Wahl, Andrew O.
Wolfson, Aaron H.
Zelop, Carolyn M.
TI ACR Appropriateness Criteria\Pretreatment Evaluation and Follow-Up of
Endometrial Cancer
SO ULTRASOUND QUARTERLY
LA English
DT Article
DE appropriateness criteria; endometrial cancer; staging; imaging;
recurrence; treatment response
ID LYMPH-NODE METASTASIS; APPARENT DIFFUSION-COEFFICIENT;
POSITRON-EMISSION-TOMOGRAPHY; TRANSVAGINAL SONOGRAPHY; MYOMETRIAL
INVASION; PREOPERATIVE ASSESSMENT; DIAGNOSTIC-ACCURACY; CERVICAL
INVASION; DEEP MYOMETRIAL; CLINICAL IMPACT
AB Endometrial cancer is the most common gynecologic and the fourth most common malignancy in women in the United States. Cross-sectional imaging plays a vital role in pretreatment assessment of endometrial cancers and should be viewed as a complementary tool for surgical evaluation and planning of these patients. Although transvaginal US remains the preferred examination for the screening purposes, MRI has emerged as the modality of choice for the staging of endometrial cancer and imaging assessment of recurrence or treatment response. A combination of dynamic contrast-enhanced and diffusion weighted MRI provides the highest accuracy for the staging. Both CT and MRI perform equivalently for assessing nodal involvement or distant metastasis. PET-CT is more appropriate for assessing lymphadenopathy in high-grade FDG-avid tumors or for clinically suspected recurrence after treatment. An appropriate use and guidelines of imaging techniques in diagnosis, staging, and detection of endometrial cancer and treatment of recurrent disease are reviewed. The American College of Radiology Appropriateness Criteria((R)) are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
C1 [Lalwani, Neeraj; Dubinsky, Theodore] Univ Washington, Sch Med, Seattle, WA 98104 USA.
[Javitt, Marcia C.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA.
[Gaffney, David K.] Univ Utah, Med Ctr, Salt Lake City, UT USA.
[Glanc, Phyllis] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada.
[Elshaikh, Mohamed A.] Henry Ford Hlth Syst, Detroit, MI USA.
[Kim, Young Bae] Tufts Med Ctr, Soc Gynecol Oncologists, Boston, MA USA.
[Lee, Larissa J.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Pannu, Harpreet K.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Royal, Henry D.] Washington Univ, Med Ctr, Mallinckrodt Inst Radiol, Soc Nucl Med & Mol Imaging, St Louis, MO 63110 USA.
[Shipp, Thomas D.] Brigham & Womens Hosp, Amer Coll Obstet & Gynecol, Boston, MA 02115 USA.
[Siegel, Cary Lynn] Washington Univ, Med Ctr, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA.
[Simpson, Lynn] Columbia Univ, Amer Coll Obstet & Gynecol, New York, NY USA.
[Wahl, Andrew O.] Univ Nebraska Med Ctr, Omaha, NE USA.
[Wolfson, Aaron H.] Univ Miami, Miami, FL USA.
[Zelop, Carolyn M.] Valley Hosp, Amer Coll Obstet & Gynecol, Ridgewood, NJ USA.
RP Lalwani, N (reprint author), Univ Washington, Dept Radiol Body Imaging, Box 359728,325 9th Ave, Seattle, WA 98104 USA.
EM neerajl@u.washington.edu
NR 64
TC 5
Z9 5
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0894-8771
EI 1536-0253
J9 ULTRASOUND Q
JI Ultrasound Q.
PD MAR
PY 2014
VL 30
IS 1
BP 21
EP 28
DI 10.1097/RUQ.0000000000000068
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AH2UZ
UT WOS:000335978500005
PM 24901775
ER
PT J
AU Bei, M
AF Bei, M.
TI KCNHI2 AND KCNJ8 INTERACTIVELY REGULATE SKIN WOUND HEALING AND
REGENERATION
SO WOUND REPAIR AND REGENERATION
LA English
DT Meeting Abstract
C1 [Bei, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Bei, M.] Shriners Burns Hosp, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1067-1927
EI 1524-475X
J9 WOUND REPAIR REGEN
JI Wound Repair Regen.
PD MAR
PY 2014
VL 22
IS 2
BP A31
EP A31
PG 1
WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery
SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery
GA AC9DV
UT WOS:000332835400018
ER
PT J
AU Bouldin, EL
Littman, AJ
Rice, K
Reiber, GE
AF Bouldin, E. L.
Littman, A. J.
Rice, K.
Reiber, G. E.
TI RURAL RESIDENCE, DUAL USE, AND CHRONIC WOUND OUTCOMES AMONG VETERANS
SO WOUND REPAIR AND REGENERATION
LA English
DT Meeting Abstract
C1 [Bouldin, E. L.; Littman, A. J.; Reiber, G. E.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Bouldin, E. L.; Littman, A. J.; Rice, K.; Reiber, G. E.] Univ Washington, Seattle, WA 98195 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 1067-1927
EI 1524-475X
J9 WOUND REPAIR REGEN
JI Wound Repair Regen.
PD MAR
PY 2014
VL 22
IS 2
BP A33
EP A33
PG 1
WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery
SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery
GA AC9DV
UT WOS:000332835400024
ER
PT J
AU Hu, MS
Januszyk, M
Hong, WX
Walmsley, GG
Colwell, A
McArdle, A
Zielins, E
Chung, MT
Gurtner, GC
Longaker, MT
Lorenz, HP
AF Hu, M. S.
Januszyk, M.
Hong, W. X.
Walmsley, G. G.
Colwell, A.
McArdle, A.
Zielins, E.
Chung, M. T.
Gurtner, G. C.
Longaker, M. T.
Lorenz, H. P.
TI GENE EXPRESSION PATHWAY ANALYSIS OF FETAL SKIN AND WOUNDS
SO WOUND REPAIR AND REGENERATION
LA English
DT Meeting Abstract
C1 [Hu, M. S.; Januszyk, M.; Hong, W. X.; Walmsley, G. G.; McArdle, A.; Zielins, E.; Chung, M. T.; Gurtner, G. C.; Longaker, M. T.; Lorenz, H. P.] Stanford Univ, Palo Alto, CA 94304 USA.
[Hu, M. S.] Univ Hawaii, Honolulu, HI 96822 USA.
[Colwell, A.] 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 1067-1927
EI 1524-475X
J9 WOUND REPAIR REGEN
JI Wound Repair Regen.
PD MAR
PY 2014
VL 22
IS 2
BP A46
EP A46
PG 1
WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery
SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery
GA AC9DV
UT WOS:000332835400075
ER
PT J
AU Mattoo, H
Della-Torre, E
Mahajan, VS
Stone, JH
Pillai, S
AF Mattoo, H.
Della-Torre, E.
Mahajan, V. S.
Stone, J. H.
Pillai, S.
TI Circulating Th2 memory cells in IgG4-related disease are restricted to a
defined subset of subjects with atopy
SO ALLERGY
LA English
DT Article
ID REGULATORY IMMUNE-REACTIONS; LACRIMAL GLAND ENLARGEMENT; PANCREATITIS
C1 [Mattoo, H.; Della-Torre, E.; Mahajan, V. S.; Pillai, S.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02129 USA.
[Della-Torre, E.] Univ Vita Salute San Raffaele, Sch Med, Unit Med & Clin Immunol, Milan, Italy.
[Stone, J. H.] Massachusetts Gen Hosp, Ctr Rheumatol Allergy & Immunol, Boston, MA 02129 USA.
RP Pillai, S (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Canc Res, 149,13th St, Boston, MA 02129 USA.
EM jhstone@partners.org; pillai@helix.mgh.harvard.edu
OI Della Torre, Emanuel/0000-0002-9192-4270
FU NIH [AI 064930, AI 076505]
FX This study was funded by grants AI 064930 and AI 076505 from the NIH to
SP.
NR 8
TC 25
Z9 26
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-4538
EI 1398-9995
J9 ALLERGY
JI Allergy
PD MAR
PY 2014
VL 69
IS 3
BP 399
EP 402
PG 4
WC Allergy; Immunology
SC Allergy; Immunology
GA AA8PW
UT WOS:000331358400015
PM 24382311
ER
PT J
AU Gordon, KB
Kimball, AB
Chau, D
Viswanathan, HN
Li, J
Revicki, DA
Kricorian, G
Ortmeier, BG
AF Gordon, K. B.
Kimball, A. B.
Chau, D.
Viswanathan, H. N.
Li, J.
Revicki, D. A.
Kricorian, G.
Ortmeier, B. G.
TI Impact of brodalumab treatment on psoriasis symptoms and health-related
quality of life: use of a novel patient-reported outcome measure, the
Psoriasis Symptom Inventory
SO BRITISH JOURNAL OF DERMATOLOGY
LA English
DT Article
ID PHASE-II; PREVALENCE
C1 [Gordon, K. B.] Northwestern Univ, Dept Dermatol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Kimball, A. B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Chau, D.; Viswanathan, H. N.; Li, J.; Kricorian, G.; Ortmeier, B. G.] Amgen Inc, Thousand Oaks, CA 91320 USA.
[Revicki, D. A.] UnitedBioSource Corp, Bethesda, MD USA.
RP Gordon, KB (reprint author), Northwestern Univ, Dept Dermatol, Feinberg Sch Med, 676 N St Clair St,Suite 1600, Chicago, IL 60611 USA.
EM Kenneth-gordon@northwestern.edu
FU Amgen Inc.
FX Funding for this study and for manuscript development was provided by
Amgen Inc.
NR 19
TC 10
Z9 10
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-0963
EI 1365-2133
J9 BRIT J DERMATOL
JI Br. J. Dermatol.
PD MAR
PY 2014
VL 170
IS 3
BP 705
EP 715
PG 11
WC Dermatology
SC Dermatology
GA AC5UJ
UT WOS:000332586100023
PM 24079852
ER
PT J
AU Mehta, SJ
Asch, DA
AF Mehta, Shivan J.
Asch, David A.
TI When are effective medications just too expensive?
SO CLEVELAND CLINIC JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID COST
C1 [Mehta, Shivan J.] Univ Penn, Perelman Sch Med, Div Gastroenterol, Philadelphia, PA 19104 USA.
[Mehta, Shivan J.; Asch, David A.] Univ Penn, Ctr Hlth Care Innovat, Philadelphia, PA 19104 USA.
[Asch, David A.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
RP Mehta, SJ (reprint author), Univ Penn, Perelman Sch Med, 1133 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA.
EM shivan.mehta@uphs.upenn.edu
OI Asch, David/0000-0002-7970-286X
NR 9
TC 1
Z9 1
U1 1
U2 1
PU CLEVELAND CLINIC
PI CLEVELAND
PA 9500 EUCLID AVE, CLEVELAND, OH 44106 USA
SN 0891-1150
EI 1939-2869
J9 CLEV CLIN J MED
JI Clevel. Clin. J. Med.
PD MAR
PY 2014
VL 81
IS 3
BP 173
EP 175
DI 10.3949/ccjm.81a.14010
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA AH1WA
UT WOS:000335911200008
PM 24591472
ER
PT J
AU Frech, T
Redd, D
Rhiannon, J
Murtaugh, M
Zeng, Q
AF Frech, T.
Redd, D.
Rhiannon, J.
Murtaugh, M.
Zeng, Q.
TI INFORMATICS CAN IDENTIFY SYSTEMIC SCLEROSIS PATIENTS AT RISK FOR
SCLERODERMA RENAL CRISIS
SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
LA English
DT Meeting Abstract
C1 [Frech, T.; Redd, D.; Murtaugh, M.; Zeng, Q.] Univ Utah, Salt Lake VAMC, Salt Lake City, UT USA.
[Rhiannon, J.] Denver VAMC, Denver, CO USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CLINICAL & EXPER RHEUMATOLOGY
PI PISA
PA VIA SANTA MARIA 31, 56126 PISA, ITALY
SN 0392-856X
J9 CLIN EXP RHEUMATOL
JI Clin. Exp. Rheumatol.
PD MAR-APR
PY 2014
VL 32
IS 2
SU 81
BP S115
EP S116
PG 2
WC Rheumatology
SC Rheumatology
GA AH2FH
UT WOS:000335936400308
ER
PT J
AU Ghassemi, P
Lagares, D
Tremblay, C
Blati, M
Baron, M
Tager, A
Kapoor, M
AF Ghassemi, P.
Lagares, D.
Tremblay, C.
Blati, M.
Baron, M.
Tager, A.
Kapoor, M.
TI EPHRIN B2 IS OVEREXPRESSED IN HUMAN SCLERODERMA SKIN AND MEDIATES
FIBROBLAST TO MYOFIBROBLAST DIFFERENTIATION, AND INDUCES FIBROSIS IN
MICE
SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
LA English
DT Meeting Abstract
C1 [Ghassemi, P.; Tremblay, C.; Blati, M.; Kapoor, M.] Univ Montreal, Montreal, PQ, Canada.
[Lagares, D.; Tager, A.] McGill Univ, Montreal, PQ, Canada.
[Baron, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CLINICAL & EXPER RHEUMATOLOGY
PI PISA
PA VIA SANTA MARIA 31, 56126 PISA, ITALY
SN 0392-856X
J9 CLIN EXP RHEUMATOL
JI Clin. Exp. Rheumatol.
PD MAR-APR
PY 2014
VL 32
IS 2
SU 81
BP S14
EP S15
PG 2
WC Rheumatology
SC Rheumatology
GA AH2FH
UT WOS:000335936400026
ER
PT J
AU Khanna, D
Gladue, H
Fitzgerald, J
Channick, R
Chung, L
Distler, O
Furst, D
Hachulla, E
Humbert, M
Langelben, D
Mathai, S
Saggars, R
Visovatti, S
McLaughlin, V
AF Khanna, D.
Gladue, H.
Fitzgerald, J.
Channick, R.
Chung, L.
Distler, O.
Furst, D.
Hachulla, E.
Humbert, M.
Langelben, D.
Mathai, S.
Saggars, R.
Visovatti, S.
McLaughlin, V.
TI RECOMMENDATIONS FOR SCREENING AND DETECTION OF CONNECTIVE-TISSUE DISEASE
ASSOCIATED PULMONARY ARTERIAL HYPERTENSION
SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
LA English
DT Meeting Abstract
C1 [Khanna, D.; Gladue, H.; Visovatti, S.; McLaughlin, V.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Fitzgerald, J.; Furst, D.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Channick, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Chung, L.] Stanford Univ, Palo Alto, CA 94304 USA.
[Distler, O.] Univ Zurich, Zurich, Switzerland.
[Hachulla, E.] Univ Hosp Lille, Lille, France.
[Humbert, M.] Univ S Paris, Paris, France.
[Langelben, D.] McGill Univ, Montreal, PQ, Canada.
[Mathai, S.] Johns Hopkins Univ, Baltimore, MD USA.
[Saggars, R.] St Joseph Hosp, Phoenix, AZ USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CLINICAL & EXPER RHEUMATOLOGY
PI PISA
PA VIA SANTA MARIA 31, 56126 PISA, ITALY
SN 0392-856X
J9 CLIN EXP RHEUMATOL
JI Clin. Exp. Rheumatol.
PD MAR-APR
PY 2014
VL 32
IS 2
SU 81
BP S20
EP S20
PG 1
WC Rheumatology
SC Rheumatology
GA AH2FH
UT WOS:000335936400039
ER
PT J
AU Bernal-Mizrachi, E
Kulkarni, RN
Scott, DK
Mauvais-Jarvis, F
Stewart, AF
Garcia-Ocana, A
AF Bernal-Mizrachi, Ernesto
Kulkarni, Rohit N.
Scott, Donald K.
Mauvais-Jarvis, Franck
Stewart, Andrew F.
Garcia-Ocana, Adolfo
TI Human beta-Cell Proliferation and Intracellular Signaling Part 2: Still
Driving in the Dark Without a Road Map
SO DIABETES
LA English
DT Article
ID HUMAN PANCREATIC-ISLETS; ESTROGEN-RECEPTOR-ALPHA; INDUCED
GENE-EXPRESSION; INSULIN-SECRETION; GROWTH-FACTOR; GLUCOSE-HOMEOSTASIS;
DIABETES-MELLITUS; IN-VIVO; MOUSE PANCREAS; ADIPOSE-TISSUE
C1 [Bernal-Mizrachi, Ernesto] Univ Michigan, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 USA.
[Bernal-Mizrachi, Ernesto] US Dept Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI USA.
[Kulkarni, Rohit N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA.
[Kulkarni, Rohit N.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Scott, Donald K.; Stewart, Andrew F.; Garcia-Ocana, Adolfo] Icahn Sch Med Mt Sinai, Diabet Obes & Metab Inst, New York, NY USA.
[Mauvais-Jarvis, Franck] Tulane Univ, Sch Med, Div Endocrinol & Metab, New Orleans, LA 70112 USA.
[Mauvais-Jarvis, Franck] Hlth Sci Ctr, New Orleans, LA USA.
[Garcia-Ocana, Adolfo] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY USA.
RP Bernal-Mizrachi, E (reprint author), Univ Michigan, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 USA.
EM ebernal@med.umich.edu; adolfo.g.ocana@mssm.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[DK084236, DK073716]; Juvenile Diabetes Research Foundation (JDRF)
[46-2010-758]; NIDDK [DK067536, DK055523, DK065149, DK069362, DK074970,
HD044405, DK77096, DK67351]; Harvard Stem Cell Institute; JDRF/Sanofi
Strategic Alliance; AstraZeneca; American Diabetes Association
[7-11-BS-128]; JDRF [17-2011-598, 1-2006-837, 1-2008-39, 34-2008-630,
47-2012-750]; March of Dimes [6-FY07-678]; NIDDK Beta Cell Biology
Consortium [U01 DK089538, DK55023]
FX The authors wish to thank the funding agencies for their essential
contribution to this work, which was supported by National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK) grants DK084236 and
DK073716 and the Juvenile Diabetes Research Foundation (JDRF)
International grant 46-2010-758 to E.B.-.M.; NIDDK grants DK067536 and
DK055523, the Harvard Stem Cell Institute, the JDRF/Sanofi Strategic
Alliance, and AstraZeneca to R.N.K.; NIDDK grant DK065149, American
Diabetes Association grant 7-11-BS-128, and JDRF grant 17-2011-598 to
D.K.S.; NIDDK grants DK069362, DK074970, and HD044405, JDRF grant
1-2006-837, and the March of Dimes grant 6-FY07-678 to F.M.-.J.; the
NIDDK Beta Cell Biology Consortium grants U01 DK089538 and DK55023, JDRF
grants 1-2008-39, 17-2011-598, and 34-2008-630 to A.F.S.; and NIDDK
grants DK77096 and DK67351 and JDRF grant 47-2012-750 to A.G.-O.
NR 94
TC 48
Z9 48
U1 0
U2 10
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
EI 1939-327X
J9 DIABETES
JI Diabetes
PD MAR
PY 2014
VL 63
IS 3
BP 819
EP 831
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AB2HQ
UT WOS:000331614200001
PM 24556859
ER
PT J
AU Mezza, T
Muscogiuri, G
Sorice, GP
Clemente, G
Hu, J
Pontecorvi, A
Holst, JJ
Giaccari, A
Kulkarni, RN
AF Mezza, Teresa
Muscogiuri, Giovanna
Sorice, Gian Pio
Clemente, Gennaro
Hu, Jiang
Pontecorvi, Alfredo
Holst, Jens J.
Giaccari, Andrea
Kulkarni, Rohit N.
TI Insulin Resistance Alters Islet Morphology in Nondiabetic Humans
SO DIABETES
LA English
DT Article
ID GLUCAGON-LIKE PEPTIDE-1; BETA-CELL MASS; GASTRIC-INHIBITORY POLYPEPTIDE;
PARTIAL PANCREATECTOMY; IN-VIVO; GLUCOSE; SECRETION; HYPERPLASIA;
EXPRESSION; APOPTOSIS
C1 [Mezza, Teresa; Hu, Jiang; Kulkarni, Rohit N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med,Brigham & Womens Hosp, Boston, MA 02115 USA.
[Mezza, Teresa; Muscogiuri, Giovanna; Sorice, Gian Pio; Pontecorvi, Alfredo; Giaccari, Andrea] Univ Cattolica Sacro Cuore, Div Endocrinol & Metab Dis, Rome, Italy.
[Clemente, Gennaro] Univ Cattolica Sacro Cuore, Dept Surg, Rome, Italy.
[Holst, Jens J.] Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Dept Biomed Sci, Panum Inst, DK-1168 Copenhagen, Denmark.
[Giaccari, Andrea] Fdn Don C Gnocchi, Milan, Italy.
RP Giaccari, A (reprint author), Univ Cattolica Sacro Cuore, Div Endocrinol & Metab Dis, Rome, Italy.
EM giaccari@rm.unicatt.it; rohit.kulkarni@joslin.harvard.edu
OI Mezza, Teresa/0000-0001-5407-9576
FU Universita Cattolica del Sacro Cuore (Fondi Ateneo Linea D.3.2 Sindrome
Metabolica); Italian Ministry of Education, University and Research
[2010JS3PMZ_011]; Fondazione Don Gnocchi; European Association for the
Study of Diabetes; Societa Italiana di Diabetologia; Laboratori
Guidotti; National Institutes of Health [R01-DK-67536]
FX This study was supported by grants to A.G. from Universita Cattolica del
Sacro Cuore (Fondi Ateneo Linea D.3.2 Sindrome Metabolica), from the
Italian Ministry of Education, University and Research (PRIN
2010JS3PMZ_011) and from Fondazione Don Gnocchi. T.M. is the recipient
of the Albert Reynolds Travel Fellowship by the European Association for
the Study of Diabetes and the Fellowship Prize by the Societa Italiana
di Diabetologia. G.P.S. is the recipient of a fellowship from Laboratori
Guidotti. Some of the reagents used in the study were supported by
National Institutes of Health grant R01-DK-67536 to R.N.K.
NR 47
TC 48
Z9 48
U1 2
U2 10
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
EI 1939-327X
J9 DIABETES
JI Diabetes
PD MAR
PY 2014
VL 63
IS 3
BP 994
EP 1007
PG 14
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AB2HQ
UT WOS:000331614200020
PM 24215793
ER
PT J
AU Bhama, PK
Weinberg, JS
Lindsay, RW
Hohman, MH
Cheney, ML
Hadlock, TA
AF Bhama, Prabhat K.
Weinberg, Julie S.
Lindsay, Robin W.
Hohman, Marc H.
Cheney, Mack L.
Hadlock, Tessa A.
TI Objective Outcomes Analysis Following Microvascular Gracilis Transfer
for Facial Reanimation A Review of 10 Years' Experience
SO JAMA FACIAL PLASTIC SURGERY
LA English
DT Article
ID PARALYSIS; NERVE
AB IMPORTANCE Objective assessment of smile outcome after microvascular free gracilis transfer is challenging, and quantification of smile outcomes in the literature is inconsistent.
OBJECTIVE To report objective excursion and symmetry outcomes from a series of free gracilis cases and investigate the predictive value of intraoperative measurements on final outcomes.
DESIGN, SETTING, AND PARTICIPANTS A retrospective medical chart review was undertaken of all patients who underwent microvascular free gracilis transfer for smile at our institution over the past 10 years.
MAIN OUTCOMES AND MEASURES Outcome measures included the following: smile excursion, angle of smile with respect to the vertical midline, and facial symmetry during repose and with smile. Measurements were obtained using an automated tool for assessment of facial landmarks (FACE-Gram). An exhaustive set of intraoperative parameters including degree of recoil of the gracilis muscle following harvest, the degree to which the muscle foreshortened during stimulation of the obturator nerve, final stretched length of the inset muscle, surgeon assessment of neurorrhaphy and pulse pressure, ischemia time, number of sutures used during neurorrhaphy, nerve used to innervate the flap, and surgeon assessment of oral commissure overcorrection were recorded and placed into a linear regression model to investigate correlations with smile.
RESULTS From March 2003 to March 2013, 154 microvascular free gracilis transfers were performed for facial reanimation at our institution, 14 (9%) of which were deemed failures. Of the remaining 140 flaps, 127 fulfilled inclusion criteria and constituted the study cohort. Smile excursion, angle excursion, and symmetry of the oral commissure at repose and with smile all improved following gracilis free flap (P < .05). Associations between selected outcomes measures and intraoperative gracilis measurements were identified.
CONCLUSIONS AND RELEVANCE Facial reanimation using free gracilis transfer results in quantifiable improvements in oral commissure excursion and facial symmetry both at rest and with smiling. Associations between contractility and internal recoil of the flap and final outcome were identified.
C1 [Bhama, Prabhat K.; Weinberg, Julie S.; Lindsay, Robin W.; Cheney, Mack L.; Hadlock, Tessa A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Div Facial Plast & Reconstruct Surg,Dept Otolaryn, Boston, MA 02114 USA.
[Bhama, Prabhat K.] Harvard Univ, Sch Publ Hlth, Boston, MA 02114 USA.
[Hohman, Marc H.] Madigan Army Med Ctr, Tacoma, WA 98431 USA.
RP Bhama, PK (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Publ Hlth,Sch Med, Div Facial Plast & Reconstruct Surg,Dept Otolaryn, 243 Charles St, Boston, MA 02114 USA.
EM pbhama@gmail.com
FU National Institutes of Health (NIH) [R01NS071067]
FX This research was supported by grant R01NS071067 from the National
Institutes of Health (NIH).
NR 8
TC 17
Z9 17
U1 0
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6076
EI 2168-6092
J9 JAMA FACIAL PLAST SU
JI JAMA Facial Plast. Surg.
PD MAR-APR
PY 2014
VL 16
IS 2
BP 85
EP 92
DI 10.1001/jamafacial.2013.2463
PG 8
WC Surgery
SC Surgery
GA AH2OX
UT WOS:000335961900003
PM 24481538
ER
PT J
AU Herr, MW
Emerick, KS
Deschler, DG
AF Herr, Marc W.
Emerick, Kevin S.
Deschler, Daniel G.
TI The Supraclavicular Artery Flap for Head and Neck Reconstruction
SO JAMA FACIAL PLASTIC SURGERY
LA English
DT Article
ID ISLAND FLAP; CERVICOHUMERAL FLAP; CONTRACTURES; EXPERIENCE
AB IMPORTANCE This study demonstrates the versatility of the supraclavicular artery (SCA) flap in head and neck reconstruction and offers technical highlights to improve the efficiency of flap harvest.
OBJECTIVES To report our series of diverse reconstructions utilizing the SCA flap and to highlight several technical aspects of flap harvest that make the procedure more safe, reliable, and efficient.
DESIGN, SETTING, AND PARTICIPANTS A retrospective review was conducted from July 2011 to December 2012 on all patients who had undergone SCA flap reconstruction of a head and neck defect at a tertiary referral center. The average follow-up time was 8 months.
INTERVENTION OR EXPOSURE Supraclavicular artery flap reconstruction of defects at various head and neck subsites.
MAIN OUTCOME AND MEASURE Reconstructive outcomes and complications were assessed and cases were reviewed to identify key aspects of flap harvest.
RESULTS Twenty-four SCA flaps were performed on defects at multiple head and neck subsites. Several technical modifications were developed to increase the safety and efficiency of flap harvest. Complications were typically self-limited and were successfully managed nonsurgically.
CONCLUSIONS AND RELEVANCE The SCA flap is a versatile and reliable reconstructive option for head and neck defects. There are 4 key steps to making the harvest of this flap safe, reliable, and efficient.
C1 [Herr, Marc W.; Emerick, Kevin S.; Deschler, Daniel G.] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Div Head & Neck Surg, Boston, MA 02114 USA.
RP Herr, MW (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Div Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA.
EM marc.w.herr@gmail.com
NR 24
TC 7
Z9 7
U1 1
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6076
EI 2168-6092
J9 JAMA FACIAL PLAST SU
JI JAMA Facial Plast. Surg.
PD MAR-APR
PY 2014
VL 16
IS 2
BP 127
EP 132
DI 10.1001/jamafacial.2013.2170
PG 6
WC Surgery
SC Surgery
GA AH2OX
UT WOS:000335961900009
PM 24370537
ER
PT J
AU Kleiss, IJ
Knox, CJ
Malo, JS
Marres, HAM
Hadlock, TA
Heaton, JT
AF Kleiss, Ingrid J.
Knox, Christopher J.
Malo, Juan S.
Marres, Henri A. M.
Hadlock, Tessa A.
Heaton, James T.
TI Whisking Recovery After Automated Mechanical Stimulation During Facial
Nerve Regeneration
SO JAMA FACIAL PLASTIC SURGERY
LA English
DT Article
ID IMPROVES FUNCTIONAL RECOVERY; RAT SKELETAL-MUSCLE; MANUAL STIMULATION;
PERIPHERAL-NERVE; ELECTRICAL-STIMULATION; MOTOR FUNCTION; CRUSH LESION;
INJURY; MOVEMENTS; REPAIR
AB IMPORTANCE Recovery from facial nerve transection is typically poor, but daily mechanical stimulation of the face in rats has been reported to remarkably enhance functional recovery after facial nerve transection and suture repair. This phenomenon needs additional investigation because of its important clinical implications.
OBJECTIVE To determine whether automated mechanical stimulation of the whisker pad improves whisking recovery after facial nerve transection and repair in a rat model.
DESIGN AND SETTING Sixty-one rats underwent unilateral facial nerve transection and suture repair and were randomized into 8 groups. Six groups received daily automated whisker or whisker pad mechanical stimulation including 0.5-, 1.5-, and 8.0-Hz patterns. Two control groups received restraint without stimulation. Treatment started on postoperative day 8, occurred 5 days per week, and lasted throughout 15 weeks of recovery. Whisking amplitude, velocity, and acceleration were quantified weekly for 15 weeks.
INTERVENTIONS Unilateral facial nerve transection, suture repair, and, for 6 groups, daily automated whisker or whisker pad mechanical stimulation.
MAIN OUTCOMES AND MEASURES Quantification of whisking amplitude, velocity, and acceleration.
RESULTS Rats receiving the low frequencies of stimulation of the whiskers or whisker pad did not demonstrate enhanced whisking recovery, and rats receiving stimulation at 8.0 Hz showed significantly worse whisking recovery compared with controls and previously published groups receiving lower dose manual stimulation.
CONCLUSIONS AND RELEVANCE Although daily manual whisker pad stimulation has been shown to enhance whisking recovery, rats in this study did not demonstrate improved whisking recovery after automated mechanical stimulation across a wide range of driving frequencies. Moreover, faster stimulation (8.0 Hz) was actually detrimental to recovery. Further work is needed to understand the relationship between stimulation patterns and the physiologic mechanisms underlying improved or worsened functional outcomes after facial nerve transection and repair.
C1 [Kleiss, Ingrid J.; Knox, Christopher J.; Malo, Juan S.; Hadlock, Tessa A.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA.
[Heaton, James T.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Kleiss, Ingrid J.; Marres, Henri A. M.] Radboud Univ Nijmegen, Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, NL-6525 ED Nijmegen, Netherlands.
RP Hadlock, TA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA.
EM tessa_hadlock@meei.harvard.edu
RI Marres, H.A.M./H-8071-2014
FU National Institutes of Health [R01NS071067]
FX This study was funded by grant R01NS071067 from the National Institutes
of Health (Drs Hadlock and Heaton).
NR 35
TC 1
Z9 1
U1 1
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6076
EI 2168-6092
J9 JAMA FACIAL PLAST SU
JI JAMA Facial Plast. Surg.
PD MAR-APR
PY 2014
VL 16
IS 2
BP 133
EP 139
DI 10.1001/jamafacial.2013.2217
PG 7
WC Surgery
SC Surgery
GA AH2OX
UT WOS:000335961900010
PM 24407357
ER
PT J
AU Haller, JF
Cavallaro, P
Hernandez, NJ
Dolat, L
Soscia, SJ
Welti, R
Grabowski, GA
Fitzgerald, ML
Freeman, MW
AF Haller, Jorge F.
Cavallaro, Paul
Hernandez, Nicholas J.
Dolat, Lee
Soscia, Stephanie J.
Welti, Ruth
Grabowski, Gregory A.
Fitzgerald, Michael L.
Freeman, Mason W.
TI Endogenous beta-glucocerebrosidase activity in Abca12(-/-) epidermis
elevates ceramide levels after topical lipid application but does not
restore barrier function
SO JOURNAL OF LIPID RESEARCH
LA English
DT Article
DE glucosylceramide; harlequin ichthyosis; skin permeability barrier;
ABCA12 antibody
ID STRATUM-CORNEUM CERAMIDES; HARLEQUIN ICHTHYOSIS; PERMEABILITY BARRIER;
GLUCOSYLCERAMIDE SYNTHASE; GAUCHER-DISEASE; KERATINOCYTE
DIFFERENTIATION; IMPROVED INHIBITORS; SKIN; MICE; MUTATIONS
AB ABCA12 mutations disrupt the skin barrier and cause harlequin ichthyosis. We previously showed Abca12(-/-) skin has increased glucosylceramide (GlcCer) and correspondingly lower amounts of ceramide (Cer). To examine why loss of ABCA12 leads to accumulation of GlcCer, de novo sphingolipid synthesis was assayed using [C-14] serine labeling in ex vivo skin cultures. A defect was found in beta-glucocerebrosidase (GCase) processing of newly synthesized GlcCer species. This was not due to a decline in GCase function. Abca12(-/-) epidermis had 5-fold more GCase protein (n = 4, P < 0.01), and a 5-fold increase in GCase activity (n = 3, P < 0.05). As with Abca12(+/+) epidermis, immunostaining in null skin showed a typical interstitial distribution of the GCase protein in the Abca12(-/-) stratum corneum. Hence, we tested whether the block in GlcCer conversion could be circumvented by topically providing GlcCer. This approach restored up to 15% of the lost Cer products of GCase activity in the Abca12(-/-) epidermis. However, this level of barrier ceramide replacement did not significantly reduce trans-epidermal water loss function.(jlr) Our results indicate loss of ABCA12 function results in a failure of precursor GlcCer substrate to productively interact with an intact GCase enzyme, and they support a model of ABCA12 function that is critical for transporting GlcCer into lamellar bodies.
C1 [Haller, Jorge F.; Cavallaro, Paul; Hernandez, Nicholas J.; Dolat, Lee; Soscia, Stephanie J.; Fitzgerald, Michael L.; Freeman, Mason W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lipid Metab Unit, Boston, MA 02114 USA.
[Haller, Jorge F.; Cavallaro, Paul; Hernandez, Nicholas J.; Dolat, Lee; Soscia, Stephanie J.; Fitzgerald, Michael L.; Freeman, Mason W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
[Welti, Ruth] Kansas State Univ, Kansas Lipid Res Ctr, Manhattan, KS 66506 USA.
[Grabowski, Gregory A.] Childrens Hosp Res Fdn, Div & Program Human Genet, Cincinnati, OH 45229 USA.
RP Fitzgerald, ML (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lipid Metab Unit, Boston, MA 02114 USA.
EM mfitzgerald@ccib.mgh.harvard.edu; mfreeman@ccib.mgh.harvard.edu
FU National Institutes of Health [RR020345, RR020345-04S1, HL112661,
HL101274, P20 RR16475]; National Science Foundation [MCB 0455318, DBI
0521587]; EPSCoR [EPS-0236913]; State of Kansas through Kansas
Technology Enterprise Corporation and Kansas State University
FX This work was supported by National Institutes of Health Grants RR020345
(M.W.F.), RR020345-04S1 (M.W.F.), HL112661 (M.L.F.), and HL101274
(M.L.F.). The Kansas Lipidomics Research Center was supported by
National Science Foundation Grants MCB 0455318 and DBI 0521587; by
EPSCoR Grant EPS-0236913 with matching support from the State of Kansas
through Kansas Technology Enterprise Corporation and Kansas State
University; and by National Institutes of Health Grant P20 RR16475.
NR 42
TC 2
Z9 2
U1 0
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0022-2275
EI 1539-7262
J9 J LIPID RES
JI J. Lipid Res.
PD MAR
PY 2014
VL 55
IS 3
BP 493
EP 503
DI 10.1194/jlr.M044941
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AH8YX
UT WOS:000336425300013
PM 24293640
ER
PT J
AU Goodman, J
Chenausky, K
AF Goodman, Janice
Chenausky, Kerry
TI CALM Pregnancy: Results of a Pilot Study of Mindfulness-Based Cognitive
Therapy for Perinatal Anxiety
SO NURSING RESEARCH
LA English
DT Meeting Abstract
C1 [Goodman, Janice] Massachusetts Gen Hosp, Inst Hlth Profess, Sch Nursing, Boston, MA 02114 USA.
NR 0
TC 1
Z9 1
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-6562
EI 1538-9847
J9 NURS RES
JI Nurs. Res.
PD MAR-APR
PY 2014
VL 63
IS 2
BP E61
EP E61
PG 1
WC Nursing
SC Nursing
GA AE6JP
UT WOS:000334098000170
ER
PT J
AU Gray-Miceli, D
Ratcliffe, S
Thomasson, A
AF Gray-Miceli, Deanna
Ratcliffe, Sarah
Thomasson, Arwin
TI Patient Level Risk Factors to Assess in Older Adult Fallers with
Orthostatic Hypotension
SO NURSING RESEARCH
LA English
DT Meeting Abstract
C1 [Gray-Miceli, Deanna] Rutgers State Univ, Coll Nursing, Piscataway, NJ 08855 USA.
[Ratcliffe, Sarah] Univ Penn, Sch Med & Biostat, Philadelphia, PA 19104 USA.
[Thomasson, Arwin] Ctr Hlth Equ Res & Promot, Philadelphia VA Med Ctr, Philadelphia, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-6562
EI 1538-9847
J9 NURS RES
JI Nurs. Res.
PD MAR-APR
PY 2014
VL 63
IS 2
BP E7
EP E8
PG 2
WC Nursing
SC Nursing
GA AE6JP
UT WOS:000334098000019
ER
PT J
AU Kutney-Lee, A
Brennan, C
Meterko, M
Ersek, M
AF Kutney-Lee, Ann
Brennan, Caitlin
Meterko, Mark
Ersek, Mary
TI Organization of Nursing and Quality of Care for Veterans at the End of
Life
SO NURSING RESEARCH
LA English
DT Meeting Abstract
C1 [Kutney-Lee, Ann] Univ Penn, Philadelphia, PA 19104 USA.
[Brennan, Caitlin] NIH, Ctr Clin, Bethesda, MD USA.
[Meterko, Mark] VA Boston Healthcare Syst, Boston, MA USA.
[Ersek, Mary] Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-6562
EI 1538-9847
J9 NURS RES
JI Nurs. Res.
PD MAR-APR
PY 2014
VL 63
IS 2
BP E129
EP E129
PG 1
WC Nursing
SC Nursing
GA AE6JP
UT WOS:000334098000355
ER
PT J
AU Malley, A
Kenner, C
Kim, T
Blakeney, B
AF Malley, Ann
Kenner, Carole
Kim, Tiffany
Blakeney, Barbara
TI Nursing's Contribution To Transitions in Care
SO NURSING RESEARCH
LA English
DT Meeting Abstract
C1 [Malley, Ann; Blakeney, Barbara] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Kenner, Carole; Kim, Tiffany] Northeastern Univ, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-6562
EI 1538-9847
J9 NURS RES
JI Nurs. Res.
PD MAR-APR
PY 2014
VL 63
IS 2
BP E121
EP E121
PG 1
WC Nursing
SC Nursing
GA AE6JP
UT WOS:000334098000334
ER
PT J
AU Mataoui, FZ
Sheldon, LK
Cooley, M
AF Mataoui, Fatma Zohra
Sheldon, Lisa Kennedy
Cooley, Mary
TI What are the Barriers to BRCA1/2 Testing Among Women at High-risk for
Breast and Ovarian Cancer? A Systematic Review
SO NURSING RESEARCH
LA English
DT Meeting Abstract
C1 [Mataoui, Fatma Zohra] Univ Massachusetts, Amherst, MA 01003 USA.
[Sheldon, Lisa Kennedy] Univ Massachusetts Boston, Boston, MA USA.
[Cooley, Mary] Univ Massachusetts Boston, Dana Farber Canc Inst, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-6562
EI 1538-9847
J9 NURS RES
JI Nurs. Res.
PD MAR-APR
PY 2014
VL 63
IS 2
BP E112
EP E112
PG 1
WC Nursing
SC Nursing
GA AE6JP
UT WOS:000334098000309
ER
PT J
AU Moriarty, H
Winter, L
Robinson, K
Piersol, C
Vause-Earland, T
Iacavone, D
True, G
Hodgson, N
Holbert, L
Newhart, B
Fishman, D
AF Moriarty, Helene
Winter, Laraine
Robinson, Keith
Piersol, Catherine
Vause-Earland, Tracey
Iacavone, Dolores
True, Gala
Hodgson, Nancy
Holbert, Laura
Newhart, Brian
Fishman, Deborah
TI Challenges in Mental Health Predictors of Community Reintegration in
Military Veterans with Mild to Moderate Traumatic Brain Injury
SO NURSING RESEARCH
LA English
DT Meeting Abstract
C1 [Moriarty, Helene] Villanova Univ, Coll Nursing, Villanova, PA 19085 USA.
[Winter, Laraine; Robinson, Keith; Iacavone, Dolores; True, Gala; Holbert, Laura; Newhart, Brian; Fishman, Deborah] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Piersol, Catherine; Vause-Earland, Tracey] Thomas Jefferson Univ, Sch Hlth Profess, Philadelphia, PA USA.
[Hodgson, Nancy] Johns Hopkins Univ, Sch Nursing, Baltimore, MD 21218 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-6562
EI 1538-9847
J9 NURS RES
JI Nurs. Res.
PD MAR-APR
PY 2014
VL 63
IS 2
BP E71
EP E72
PG 2
WC Nursing
SC Nursing
GA AE6JP
UT WOS:000334098000199
ER
PT J
AU Moriarty, H
Winter, L
Piersol, C
Vause-Earland, T
Robinson, K
Lacavone, D
True, G
Holbert, L
Newhart, B
Hodgson, N
Fishman, D
AF Moriarty, Helene
Winter, Laraine
Piersol, Catherine
Vause-Earland, Tracey
Robinson, Keith
Lacavone, Dolores
True, Gala
Holbert, Laura
Newhart, Brian
Hodgson, Nancy
Fishman, Deborah
TI Using Dyadic Analyses with Veterans with Traumatic Brain Injury and
their Family Members: Implications for Family Relationships
SO NURSING RESEARCH
LA English
DT Meeting Abstract
C1 [Moriarty, Helene] Villanova Univ, Coll Nursing, Villanova, PA 19085 USA.
[Winter, Laraine; Robinson, Keith; Lacavone, Dolores; Holbert, Laura; Newhart, Brian; Fishman, Deborah] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Piersol, Catherine; Vause-Earland, Tracey] Thomas Jefferson Univ, Sch Hlth Profess, Philadelphia, PA USA.
[True, Gala] CHERP, Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Hodgson, Nancy] Johns Hopkins Univ, Sch Nursing, Baltimore, MD 21218 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-6562
EI 1538-9847
J9 NURS RES
JI Nurs. Res.
PD MAR-APR
PY 2014
VL 63
IS 2
BP E11
EP E12
PG 2
WC Nursing
SC Nursing
GA AE6JP
UT WOS:000334098000030
ER
PT J
AU Mosadegh, S
Farnum, K
Kline, N
AF Mosadegh, Sara
Farnum, Karen
Kline, Nancy
TI The Red Bag Review: A Medication Reconciliation Initiative
SO NURSING RESEARCH
LA English
DT Meeting Abstract
C1 [Mosadegh, Sara; Farnum, Karen] Northeastern Univ, Boston, MA USA.
[Kline, Nancy] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-6562
EI 1538-9847
J9 NURS RES
JI Nurs. Res.
PD MAR-APR
PY 2014
VL 63
IS 2
BP E38
EP E38
PG 1
WC Nursing
SC Nursing
GA AE6JP
UT WOS:000334098000107
ER
PT J
AU Poghosyan, H
Joseph, J
Bell, J
Cooley, M
AF Poghosyan, Hermine
Joseph, Jill
Bell, Janice
Cooley, Mary
TI The Association Between Having a First-degree Family History of Cancer
and Smoking Status
SO NURSING RESEARCH
LA English
DT Meeting Abstract
C1 [Poghosyan, Hermine] Univ Massachusetts Boston, Boston, MA USA.
[Joseph, Jill; Bell, Janice] Univ Calif Davis, Davis, CA USA.
[Cooley, Mary] Dana Farber Canc Inst, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-6562
EI 1538-9847
J9 NURS RES
JI Nurs. Res.
PD MAR-APR
PY 2014
VL 63
IS 2
BP E71
EP E71
PG 1
WC Nursing
SC Nursing
GA AE6JP
UT WOS:000334098000198
ER
PT J
AU Stetler, RA
Leak, RK
Gan, Y
Li, PY
Zhang, F
Hu, XM
Jing, Z
Chen, J
Zigmond, MJ
Gao, YQ
AF Stetler, R. Anne
Leak, Rehana K.
Gan, Yu
Li, Peiying
Zhang, Feng
Hu, Xiaoming
Jing, Zheng
Chen, Jun
Zigmond, Michael J.
Gao, Yanqin
TI Preconditioning provides neuroprotection in models of CNS disease:
Paradigms and clinical significance
SO PROGRESS IN NEUROBIOLOGY
LA English
DT Review
DE Preconditioning; Neuroprotection; Ischemia; Traumatic brain injury
ID FOCAL CEREBRAL-ISCHEMIA; TRAUMATIC BRAIN-INJURY; METHYL-D-ASPARTATE;
OXYGEN-GLUCOSE DEPRIVATION; MESENCHYMAL STEM-CELLS; K-ATP CHANNEL;
HYPOTHERMIC CIRCULATORY ARREST; SENSITIVE POTASSIUM CHANNELS; NEONATAL
HYPOXIA-ISCHEMIA; CEREBELLAR GRANULE CELLS
AB Preconditioning is a phenomenon in which brief episodes of a sublethal insult induce robust protection against subsequent lethal injuries. Preconditioning has been observed in multiple organisms and can occur in the brain as well as other tissues. Extensive animal studies suggest that the brain can be preconditioned to resist acute injuries, such as ischemic stroke, neonatal hypoxia/ischemia, surgical brain injury, trauma, and agents that are used in models of neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. Effective preconditioning stimuli are numerous and diverse, ranging from transient ischemia, hypoxia, hyperbaric oxygen, hypothermia and hyperthermia, to exposure to neurotoxins and pharmacological agents. The phenomenon of "cross-tolerance," in which a sublethal stress protects against a different type of injury, suggests that different preconditioning stimuli may confer protection against a wide range of injuries. Research conducted over the past few decades indicates that brain preconditioning is complex, involving multiple effectors such as metabolic inhibition, activation of extra- and intracellular defense mechanisms, a shift in the neuronal excitatory/inhibitory balance, and reduction in inflammatory sequelae. An improved understanding of brain preconditioning should help us identify innovative therapeutic strategies that prevent or at least reduce neuronal damage in susceptible patients. In this review, we focus on the experimental evidence of preconditioning in the brain and systematically survey the models used to develop paradigms for neuroprotection, and then discuss the clinical potential of brain preconditioning. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Stetler, R. Anne; Gan, Yu; Li, Peiying; Zhang, Feng; Chen, Jun; Zigmond, Michael J.; Gao, Yanqin] Fudan Univ, Shanghai Med Coll, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China.
[Stetler, R. Anne; Gan, Yu; Li, Peiying; Zhang, Feng; Chen, Jun; Zigmond, Michael J.; Gao, Yanqin] Fudan Univ, Shanghai Med Coll, Inst Brain Sci, Shanghai 200032, Peoples R China.
[Stetler, R. Anne; Gan, Yu; Li, Peiying; Zhang, Feng; Hu, Xiaoming; Jing, Zheng; Chen, Jun; Zigmond, Michael J.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA.
[Stetler, R. Anne; Gan, Yu; Li, Peiying; Zhang, Feng; Hu, Xiaoming; Jing, Zheng; Chen, Jun; Zigmond, Michael J.] Univ Pittsburgh, Sch Med, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA.
[Leak, Rehana K.] Duquesne Univ, Mylan Sch Pharm, Div Pharmaceut Sci, Pittsburgh, PA 15282 USA.
[Stetler, R. Anne; Zhang, Feng; Hu, Xiaoming; Jing, Zheng; Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Educ & Clin Ctr, Pittsburgh, PA 15261 USA.
RP Gao, YQ (reprint author), Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China.
EM yqgao@shmu.edu.cn
RI Gao, Yanqin/I-6790-2016;
OI Gao, Yanqin/0000-0002-4915-9819; Leak, Rehana/0000-0003-2817-7417
FU National Institutes of Health/NINDS [NS36736, NS43802, NS56118, NS45048,
NS070825]; VA Merit Review Grant; Chinese Natural Science Foundation
[81020108021, 81171149, 81371306, 30870794, 81228008, 81271276]; VA
Career Scientist Award; RK Mellon Endowed Chair from the University of
Pittsburgh Medical Center; Changjiang Chair Professorship from the
Chinese Ministry of Education; International Distinguished Professorship
from the Chinese Ministry of Education [MS2011FDDX025]
FX This work was supported by National Institutes of Health/NINDS Grants
NS36736, NS43802, NS56118, and NS45048 (to JC) and NS070825 (to MZ and
JC), the VA Merit Review Grant (to JC), and Chinese Natural Science
Foundation grants 81020108021, 81171149, 81371306 and 30870794 (to YG);
81228008 (to JC); 81271276 (to FZ). J.C. is a recipient of the VA Career
Scientist Award, the RK Mellon Endowed Chair from the University of
Pittsburgh Medical Center, and the Changjiang Chair Professorship from
the Chinese Ministry of Education. M.Z. is the recipient of the
International Distinguished Professorship from the Chinese Ministry of
Education (MS2011FDDX025). We thank Ms. Carol Culver for excellent
editorial assistance and Ms. Pat Strickler for secretarial support.
NR 415
TC 55
Z9 58
U1 4
U2 38
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0301-0082
J9 PROG NEUROBIOL
JI Prog. Neurobiol.
PD MAR
PY 2014
VL 114
BP 58
EP 83
DI 10.1016/j.pneurobio.2013.11.005
PG 26
WC Neurosciences
SC Neurosciences & Neurology
GA AH1JQ
UT WOS:000335876800004
PM 24389580
ER
PT J
AU Ellingson, LD
Koltyn, KF
Kim, JS
Cook, DB
AF Ellingson, Laura D.
Koltyn, Kelli F.
Kim, Jee-Seon
Cook, Dane B.
TI Does exercise induce hypoalgesia through conditioned pain modulation?
SO PSYCHOPHYSIOLOGY
LA English
DT Article
ID NOXIOUS INHIBITORY CONTROLS; BLOOD-PRESSURE; PHYSICAL-ACTIVITY;
FIBROMYALGIA SYNDROME; ISOMETRIC-EXERCISE; UNITED-STATES; MUSCLE PAIN;
ACCELEROMETER; ANALGESIA; MECHANISMS
C1 [Ellingson, Laura D.; Cook, Dane B.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
[Ellingson, Laura D.; Koltyn, Kelli F.; Cook, Dane B.] Univ Wisconsin, Dept Kinesiol, Madison, WI 53706 USA.
[Kim, Jee-Seon] Univ Wisconsin, Dept Educ Psychol, Madison, WI 53706 USA.
RP Cook, DB (reprint author), Univ Wisconsin, Dept Kinesiol, 2000 Observ Dr, Madison, WI 53706 USA.
EM dcook@education.wisc.edu
NR 48
TC 16
Z9 17
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0048-5772
EI 1469-8986
J9 PSYCHOPHYSIOLOGY
JI Psychophysiology
PD MAR
PY 2014
VL 51
IS 3
BP 267
EP 276
PG 10
WC Psychology, Biological; Neurosciences; Physiology; Psychology;
Psychology, Experimental
SC Psychology; Neurosciences & Neurology; Physiology
GA AA8OZ
UT WOS:000331356100006
PM 24354707
ER
PT J
AU Desai, NS
Saboo, SS
Khandelwal, A
Ricci, JA
AF Desai, Naman S.
Saboo, Sachin S.
Khandelwal, Ashish
Ricci, Joseph A.
TI Pneumosinus Dilatans: Is It More Than an Aesthetic Concern?
SO JOURNAL OF CRANIOFACIAL SURGERY
LA English
DT Article
DE Pneumosinus dilatans; paranasal sinuses; meningioma; arachnoid cyst;
orbital tumor
ID FRONTAL-SINUS; ETIOLOGY; MENINGIOMAS; PRESSURE; SIGN
AB Background Pneumosinus dilatans (PD) is a pathologic condition involving the hyperaeration of one or several of the paranasal sinuses that can lead to significant deformation of the overlying bone. Although the presenting complaint of patients with PD is most commonly aesthetic in nature, the condition has also been associated with intracranial tumors and several other serious conditions.
Materials and Methods A meta-analysis of all available clinical publications on the subject of PD was conducted. Patients were categorized on the basis of their sinus involvement. Associated conditions were also identified and categorized. The resulting data were used to further characterize the condition and describe previously unreported associations between PD and other conditions.
Results To date, a total of 123 cases of PD have been reported. The frontal sinus was the most commonly involved (63%), followed by the sphenoid sinus (24%), maxillary sinus (20%), and ethmoid sinus (19%). Of patients with symptomatic PD of the frontal sinus, 25% had intracranial pathology (meningioma or arachnoid cyst or orbital tumor). Patients with sphenoid PD had an 83% chance of having associated diagnosis of visual loss, meningioma, or arachnoid cyst, whereas patients with ethmoid PD had 83% chance of having associated diagnosis of exophthalmos, vision loss, or arachnoid cyst.
Conclusions Although the presenting complaint of patients with PD is most commonly aesthetic in nature, a significant percentage may have an associated diagnosis. Health care providers must be able to recognize the condition and carry out the appropriate clinical evaluation to avoid missing an associated diagnosis.
C1 [Desai, Naman S.; Saboo, Sachin S.; Khandelwal, Ashish] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
[Desai, Naman S.; Saboo, Sachin S.; Khandelwal, Ashish; Ricci, Joseph A.] Harvard Univ, Sch Med, Boston, MA USA.
[Ricci, Joseph A.] Massachusetts Gen Hosp, Dept Surg, Div Plast Surg, Boston, MA 02114 USA.
RP Ricci, JA (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Plast Surg, WACC 435,55 Fruit St, Boston, MA 02114 USA.
EM jaricci@partners.org
NR 23
TC 5
Z9 5
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1049-2275
EI 1536-3732
J9 J CRANIOFAC SURG
JI J. Craniofac. Surg.
PD MAR
PY 2014
VL 25
IS 2
BP 418
EP 421
DI 10.1097/SCS.0000000000000694
PG 4
WC Surgery
SC Surgery
GA AG4IB
UT WOS:000335381800067
PM 24561372
ER
PT J
AU Doumit, GD
Junewicz, A
Yaremchuk, M
AF Doumit, Gaby D.
Junewicz, Alexandra
Yaremchuk, Michael
TI The Temporoparietal Adipofascial Flap for the Correction of Recurrent
Idiopathic Enophthalmos
SO JOURNAL OF CRANIOFACIAL SURGERY
LA English
DT Article
DE Temporoparietal adipofascial flap; enophthalmos
ID ORBITAL RECONSTRUCTION
AB Enophthalmos, the posterior displacement of a normal-size ocular globe relative to the orbital cavity, is usually repaired using autogenous grafts or alloplastic materials. We present the case of a 40-year-old man with bilateral idiopathic enophthalmos whose symptoms recurred 8 years after initial successful surgical repair. We describe the successful and safe use of a bilateral temporoparietal adipofascial flap in the treatment of recurrent idiopathic enophthalmos.
C1 [Doumit, Gaby D.; Junewicz, Alexandra] Cleveland Clin, Dept Plast Surg, Inst Dermatol & Plast Surg, Cleveland, OH 44195 USA.
[Yaremchuk, Michael] Massachusetts Gen Hosp, Dept Surg, Div Plast & Reconstruct Surg, Boston, MA 02114 USA.
RP Doumit, GD (reprint author), Cleveland Clin, Dept Plast Surg, Inst Dermatol & Plast Surg, 9500 Euclid Ave,Suite A60, Cleveland, OH 44195 USA.
EM doumitg@ccf.org
NR 10
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1049-2275
EI 1536-3732
J9 J CRANIOFAC SURG
JI J. Craniofac. Surg.
PD MAR
PY 2014
VL 25
IS 2
BP 676
EP 678
DI 10.1097/SCS.0000000000000490
PG 3
WC Surgery
SC Surgery
GA AG4IB
UT WOS:000335381800142
PM 24621720
ER
PT J
AU Kadayifci, A
Atar, M
Parlar, S
Balkan, A
Koruk, I
Koruk, M
AF Kadayifci, Abdurrahman
Atar, Mustafa
Parlar, Serap
Balkan, Ayhan
Koruk, Irfan
Koruk, Mehmet
TI Transnasal Endoscopy is Preferred by Transoral Endoscopy Experienced
Patients
SO JOURNAL OF GASTROINTESTINAL AND LIVER DISEASES
LA English
DT Article
DE Transnasal endoscopy; ultrathin endoscope; unsedated endoscopy;
tolerability
ID UPPER GASTROINTESTINAL ENDOSCOPY; UNSEDATED TRANSNASAL;
RANDOMIZED-TRIAL; CONVENTIONAL EGD; OLDER PATIENTS;
ESOPHAGOGASTRODUODENOSCOPY; SEDATION; ACCEPTABILITY
AB Background & Aims: Both unsedated transoral endoscopy (TOE) and sedated TOE have some drawbacks in clinical practice. Unsedated transnasal endoscopy (TNE) has been suggested as an alternative to both methods. This study aimed to determine the advantages of TNE in patients who have previously undergone unsedated conventional TOE.
Methods: Patients who had received an unsedated TOE in the last 12 months and were scheduled for a second upper endoscopy were included. They were randomized to undergo either unsedated TOE, using a standard endoscope, or unsedated TNE, using an ultrathin endoscope. Post-procedure, patients were asked to complete a questionnaire to assess pain, discomfort and acceptability of the procedure, and to compare the current procedure with their previous unsedated TOE. Endoscope insertion rate, procedure duration, and side-effects were recorded.
Results: Each group included 50 patients. With the exception of nasal pain, the tolerability and acceptance were significantly greater in the unsedated TNE group. Significantly more TNE patients (82%) found the current endoscopic procedure to be better than their previous TOE when compared with patients who had received a second TOE (12%). A repeat procedure was significantly more acceptable for TNE patients when compared to the TOE group (68% vs.16%). The duration of endoscopy was significantly shorter in TOE than in TNE (p<0.05). Endoscope insertion failed in 4% and mild epistaxis was observed in 4% of TNE patients.
Conclusion: Unsedated TNE was better tolerated in endoscopy experienced patients when compared with unsedated TOE. The majority of patients found TNE more acceptable and preferable to TOE, suggesting that TNE should become a more common practice in clinics when applicable.
C1 [Kadayifci, Abdurrahman; Balkan, Ayhan; Koruk, Irfan; Koruk, Mehmet] Gaziantep Univ, Div Gastroenterol, Fac Med, Gaziantep, Turkey.
[Atar, Mustafa] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol, Boston, MA USA.
[Parlar, Serap] Gaziantep Univ, Dept Internal Med Nursing, Fac Hlth Sci, Gaziantep, Turkey.
RP Kadayifci, A (reprint author), Massachusetts Gen Hosp, 3-H GI Associates,Zero Emerson Pl,Blossom St, Boston, MA 02114 USA.
EM akadayifci@mgh.harvard.edu
NR 27
TC 3
Z9 3
U1 1
U2 3
PU MEDICAL UNIV PRESS
PI CLUJ-NAPOCA
PA 3RD MEDICAL CLINIC, STR CROITORILOR NO 19-21, CLUJ-NAPOCA, 400162,
ROMANIA
SN 1841-8724
EI 1842-1121
J9 J GASTROINTEST LIVER
JI J. Gastrointest. Liver Dis.
PD MAR
PY 2014
VL 23
IS 1
BP 27
EP 31
PG 5
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AH1JY
UT WOS:000335877600008
PM 24689093
ER
PT J
AU Peraino, JS
Zhang, HP
Rajasekera, PV
Wei, M
Madsen, JC
Sachs, DH
Huang, CA
Wang, ZR
AF Peraino, Jaclyn Stromp
Zhang, Huiping
Rajasekera, Priyani V.
Wei, Min
Madsen, Joren C.
Sachs, David H.
Huang, Christene A.
Wang, Zhirui
TI Diphtheria toxin-based bivalent human IL-2 fusion toxin with improved
efficacy for targeting human CD25(+) cells
SO JOURNAL OF IMMUNOLOGICAL METHODS
LA English
DT Article
DE Human IL-2; Diphtheria toxin; Fusion toxin; Regulatory T cell; Pichia
pastoris expression
ID REGULATORY T-CELLS; YEAST PICHIA-PASTORIS; DENILEUKIN DIFTITOX; PORCINE
CTLA-4; IMMUNOTOXIN; EXPRESSION; PURIFICATION; MELANOMA; DELIVERY;
CYTOSOL
AB Regulatory T cells (Treg) constitute a major inhibitory cell population which suppresses immune responses. Thus, Treg have proven to be key players in the induction of transplantation tolerance, protection from autoimmune disease and prevention of the development of effective anti-tumor immune reactions. Treg express high levels of the high affinity interleukin-2 receptor (IL-2R) consisting of IL-2R alpha. (CD25) together with IL-2R beta (CD122) and the common gamma-chain (CD132). An effective reagent capable of depleting Treg in vivo would facilitate better cancer treatment and allow mechanistic studies of the role of Treg in transplantation tolerance and the development of autoimmune disease. In this study, we have developed a novel bivalent human IL-2 fusion toxin along with an Ontak (R)-like monovalent human IL-2 fusion toxin and compared the functional ability of these reagents in vitro. Here we show that genetically linking two human IL-2 domains in tandem, thereby generating a bivalent fusion toxin, results in significantly improved capacity in targeting human CD25(+) cells in vitro. Binding analysis by flow cytometry showed that the bivalent human IL-2 fusion toxin has notably increased affinity for human CD25(+) cells. In vitro functional analysis demonstrated that the bivalent isoform has an increased potency of approximately 2 logs in inhibiting cellular proliferation and protein synthesis in human CD25(+) cells compared to the monovalent human IL-2 fusion toxin. Additionally, we performed two inhibition assays in order to verify that the fusion toxins target the cells specifically through binding of the human IL-2 domain of the fusion toxin to the human IL-2 receptor on the cell surface. These results demonstrated that 1) both monovalent and bivalent human IL-2 fusion toxins are capable of blocking the binding of biotinylated human IL-2 to human CD25 by flow cytometry; and 2) human IL-2 blocked the fusion toxins from inhibiting protein synthesis and cellular proliferation in vitro, thus confirming that the human IL-2 fusion toxins target the cells specifically through binding to the human IL-2 receptor. We believe that the bivalent human IL-2 fusion toxin will be a more potent, and therefore, more optimal agent than the current clinically-used monovalent fusion toxin (denileukin diftitox, Ontak (R)) for in vivo depletion of Treg. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Peraino, Jaclyn Stromp; Zhang, Huiping; Rajasekera, Priyani V.; Wei, Min; Madsen, Joren C.; Sachs, David H.; Huang, Christene A.; Wang, Zhirui] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA.
[Peraino, Jaclyn Stromp; Zhang, Huiping; Rajasekera, Priyani V.; Wei, Min; Madsen, Joren C.; Sachs, David H.; Huang, Christene A.; Wang, Zhirui] Harvard Univ, Sch Med, Boston, MA USA.
[Peraino, Jaclyn Stromp; Zhang, Huiping; Rajasekera, Priyani V.; Wei, Min; Sachs, David H.; Huang, Christene A.; Wang, Zhirui] MGH DF HCC Recombinant Prot Express & Purificat C, Boston, MA USA.
RP Wang, ZR (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bldg 149-6113,13th St, Boston, MA 02129 USA.
EM zhirui.wang@tbrc.mgh.harvard.edu
FU Dana Farber/Harvard Cancer Center
FX The work was supported in part by a Dana Farber/Harvard Cancer Center
Core development grant. We would like to thank Angimmune LLC for kindly
providing the diphtheria toxin resistant yeast Pichia pastoris strain
and the codon-optimized DT390 DNA. We would like to thank Dr. Robert
Harrison for generously providing the HUT 102/6TG cell line. We would
like to thank Edward Harrington for technical assistance, and Dr. Bob
Hawley and Sharon Germana for their intensive manuscript review.
NR 21
TC 2
Z9 2
U1 1
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-1759
EI 1872-7905
J9 J IMMUNOL METHODS
JI J. Immunol. Methods
PD MAR
PY 2014
VL 405
BP 57
EP 66
DI 10.1016/j.jim.2014.01.008
PG 10
WC Biochemical Research Methods; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA AG7PA
UT WOS:000335608900007
PM 24462799
ER
PT J
AU Wellinghoff, MA
Bunchman, AM
Dean, JC
AF Wellinghoff, Molly A.
Bunchman, Alison M.
Dean, Jesse C.
TI Gradual mechanics-dependent adaptation of medial gastrocnemius activity
during human walking
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
DE dual-task walking; locomotion; motor adaptation; muscle activity
ID MUSCLE-ACTIVITY; STEP FREQUENCY; PROLONGED WALKING; TENDON VIBRATION;
MOTOR ADAPTATION; DOWNHILL WALKING; ACHILLES-TENDON; UPHILL WALKING;
HUMAN MOVEMENT; SOLEUS MUSCLE
AB While performing a simple bouncing task, humans modify their preferred movement period and pattern of plantarflexor activity in response to changes in system mechanics. Over time, the preferred movement pattern gradually adapts toward the resonant frequency. The purpose of the present experiments was to determine whether humans undergo a similar process of gradually adapting their stride period and plantarflexor activity after a change in mechanical demand while walking. Participants walked on a treadmill while we measured stride period and plantarflexor activity (medial gastrocnemius and soleus). Plantarflexor activity during stance was divided into a storage phase (30-65% stance) and a return phase (65-100% stance) based on when the Achilles tendon has previously been shown to store and return mechanical energy. Participants walked either on constant inclines (0%, 1%, 5%, 9%) or on a variable incline (0-1%) for which they were unaware of the incline changes. For variable-incline trials, participants walked under both single-task and dual-task conditions in order to vary the cognitive load. Both stride period and plantarflexor activity increased at steeper inclines. During single-task walking, small changes in incline were followed by gradual adaptation of storage-phase medial gastrocnemius activity. However, this adaptation was not present during dual-task walking, indicating some level of cognitive involvement. The observed adaptation may be the result of using afferent feedback in order to optimize the contractile conditions of the plantarflexors during the stance phase. Such adaptation could serve to improve metabolic economy but may be limited in clinical populations with disrupted proprioception.
C1 [Wellinghoff, Molly A.; Bunchman, Alison M.; Dean, Jesse C.] Med Univ S Carolina, Div Phys Therapy, Coll Hlth Profess, Charleston, SC 29425 USA.
[Dean, Jesse C.] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA.
RP Dean, JC (reprint author), 77 President St,MSC700, Charleston, SC 29425 USA.
EM deaje@musc.edu
OI Dean, Jesse/0000-0003-2034-4217
FU Department of Veterans Affairs, Office of Research and Development,
Rehabilitation Research and Development Service [1IK2RX000750-01A1];
National Institute of Child Health and Human Development [1R21
HD-064964-01A1]
FX This study was partially supported by the Department of Veterans
Affairs, Office of Research and Development, Rehabilitation Research and
Development Service through Grant 1IK2RX000750-01A1. This study was also
partially supported by the National Institute of Child Health and Human
Development through Grant 1R21 HD-064964-01A1.
NR 62
TC 1
Z9 1
U1 1
U2 4
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
EI 1522-1598
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD MAR
PY 2014
VL 111
IS 5
BP 1120
EP 1131
DI 10.1152/jn.00251.2013
PG 12
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA AG8LM
UT WOS:000335669900022
PM 24335207
ER
PT J
AU Li, PY
Tsai, TY
Li, JS
Wang, SB
Zhang, Y
Kwon, YM
Rubash, HE
Li, GA
AF Li, Pingyue
Tsai, Tsung-Yuan
Li, Jing-Sheng
Wang, Shaobai
Zhang, Yu
Kwon, Young-Min
Rubash, Harry E.
Li, Guoan
TI Gender analysis of the anterior femoral condyle geometry of the knee
SO KNEE
LA English
DT Article
DE Anterior femoral condyle; TKA; Gender-specific knee
ID ANATOMIC VARIATIONS; FEMALE KNEE; ARTHROPLASTY; DESIGN; STIFFNESS
AB Background: No study has used 3-D anatomic knee models to investigate the gender differences in anterior femoral condyles. Therefore, this study aims to determine the morphologic differences between genders in anterior femoral condyles of the knees using 3-D anatomic knee models.
Methods: Ninety-six male and sixty-five female 3D anatomic knee models were used to measure lateral and medial anterior condyle heights, anterior trochlear groove heights, and anterior condyle width, which were normalized by the anterior-posterior and medial-lateral dimensions of the knee, respectively. The shape of anterior condyle groove was also analyzed.
Results: The mean lateral anterior condyle height, medial anterior condyle height and anterior condyle width of females were 6.6 +/- 1.8 mm, 2.0 +/- 2.3 mm, and 44.7 +/- 4.2 mm, respectively. These data were significantly smaller (p < 0.05) than those of males (7.7 +/- 1.8 mm, 2.9 +/- 2.0 mm and 50.0 +/- 3.4 mm). However, after normalizing by the femur size, the aspect ratios had no gender differences. Both the ranges of lateral and medial condyle of females were significantly smaller than those of males, and the geometry curve of anterior condyle was different between genders.
Conclusion: Although the gender differences in anterior femoral condyle sizes no longer existed after normalization with the femur size, the shape and the peak position of anterior condyle groove still have gender differences. The data may have important implications on the current debate of gender-specific TKAs. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Li, Pingyue; Tsai, Tsung-Yuan; Li, Jing-Sheng; Wang, Shaobai; Kwon, Young-Min; Rubash, Harry E.; Li, Guoan] Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA.
[Li, Pingyue; Tsai, Tsung-Yuan; Li, Jing-Sheng; Wang, Shaobai; Kwon, Young-Min; Rubash, Harry E.; Li, Guoan] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Li, Pingyue; Zhang, Yu] Guangzhou Mil Command, Guangzhou Gen Hosp, Dept Orthopaed Surg, Guangzhou 510010, Guangdong, Peoples R China.
RP Li, GA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Bioengn Lab, 55 Fruit St,GRJ-1215, Boston, MA 02114 USA.
EM gli1@partners.org
OI Tsai, Tsung-Yuan/0000-0003-1522-2987
NR 22
TC 3
Z9 4
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0968-0160
EI 1873-5800
J9 KNEE
JI Knee
PD MAR
PY 2014
VL 21
IS 2
BP 529
EP 533
DI 10.1016/j.knee.2013.12.001
PG 5
WC Orthopedics; Sport Sciences; Surgery
SC Orthopedics; Sport Sciences; Surgery
GA AG7SS
UT WOS:000335619500036
PM 24462107
ER
PT J
AU Wang, W
Tsai, TY
Yue, B
Kwon, YM
Li, G
AF Wang, Wei
Tsai, Tsung-Yuan
Yue, Bin
Kwon, Young-Min
Li, Guoan
TI Posterior femoral condylar offsets of a Chinese population
SO KNEE
LA English
DT Article
DE Knee; Knee replacement; Arthroplasty; Posterior condylar offset;
Posterior condylar offset ratio
ID TOTAL KNEE ARTHROPLASTY; FLEXION; RANGE; KINEMATICS; DESIGN; MOTION;
JOINTS; REPLACEMENT; PROSTHESES; PARAMETER
AB Background: The effect of posterior condylar offset (PCO) on maximal flexion of the knee after TKA is controversial. Another parameter, the posterior condylar offset ratio (PCOR), has been recently introduced to describe the posterior condylar geometry. This study measured the posterior femoral condyle geometry of a Chinese population and compared with those of a Western population published in the literature.
Methods: We measured the PCO and PCOR of 100 Chinese knees (50 males, 50 females). The distances from the anterior and posterior femoral shaft cortex line to the most posterior femoral condyle tangent line were defined as the anterior-posterior dimension (ACP) and posterior condylar offset (PCO). The PCOR was calculated as PCO/ACP. The measured PCO and PCOR were compared to those of a Western population reported in the literature.
Results: The PCOs were 25.80 +/- 2.71 and 2732 +/- 234 mm for the Chinese females and males, respectively, where the PCO of the females was significantly smaller than that of the males (p < 0.05). The PCORs were 0.47 +/- 0.04 and 0.46 +/- 0.03 for the Chinese females and males, respectively, where the PCORs were similar among the Chinese males and females (p > 0.05).
Conclusions: While the PCO of the Chinese females was smaller than that of the males, their PCORs were similar. Compared to the data of a Western population reported in literature, the PCO of the Chinese population is significantly smaller, but the PCOR is significantly larger. (c) 2013 Elsevier B.V. All rights reserved.
C1 [Wang, Wei; Tsai, Tsung-Yuan; Kwon, Young-Min; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02114 USA.
[Wang, Wei] Xi An Jiao Tong Univ, Dept Orthopaed Surg, Affiliated Hosp 2, Sch Med, Xian 710049, Shaanxi Provinc, Peoples R China.
[Yue, Bin] Shanghai Ninth Peoples Hosp, Dept Orthopaed Surg, Shanghai, Peoples R China.
RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA.
EM gli1@partners.org
OI Tsai, Tsung-Yuan/0000-0003-1522-2987
FU Department of Orthpaedic Surgery of Massachusetts General Hospital;
Interdisciplinary Research Fund of Xi'an Jiaotong University [8143027]
FX The support of the Department of Orthpaedic Surgery of Massachusetts
General Hospital and the Interdisciplinary Research Fund of Xi'an
Jiaotong University (no. 8143027) was greatly appreciated.
NR 30
TC 2
Z9 2
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0968-0160
EI 1873-5800
J9 KNEE
JI Knee
PD MAR
PY 2014
VL 21
IS 2
BP 553
EP 556
DI 10.1016/j.knee.2013.03.010
PG 4
WC Orthopedics; Sport Sciences; Surgery
SC Orthopedics; Sport Sciences; Surgery
GA AG7SS
UT WOS:000335619500041
PM 23587633
ER
PT J
AU Blashill, AJ
Safren, SA
AF Blashill, Aaron J.
Safren, Steven A.
TI Sexual Orientation and Anabolic-Androgenic Steroids in US Adolescent
Boys
SO PEDIATRICS
LA English
DT Article
DE sexual orientation; anabolic-androgenic steroids; adolescents; boys
ID PROBLEM BEHAVIORS; DOPING AGENTS; MENTAL-HEALTH; DRUG-USE; MINORITY;
ABUSE; GAY; VICTIMIZATION; METAANALYSIS; SUICIDALITY
AB OBJECTIVES:We compared the lifetime prevalence of anabolic-androgenic steroid (AAS) misuse among sexual minority versus heterosexual US adolescent boys, and secondarily, sought to explore possible intermediate variables that may explain prevalence differences.METHODS:Participants were 17250 adolescent boys taken from a pooled data set of the 14 jurisdictions from the 2005 and 2007 Youth Risk Behavior Surveys that assessed sexual orientation. Data were analyzed for overall prevalence of AAS misuse and possible intermediary risk factors.RESULTS:Sexual minority adolescent boys were at an increased odds of 5.8 (95% confidence interval 4.1-8.2) to report a lifetime prevalence of AAS (21% vs 4%) compared with their heterosexual counterparts, P < .001. Exploratory analyses suggested that increased depressive symptoms/suicidality, victimization, and substance use contributed to this disparity.CONCLUSIONS:This is the first known study to test and find substantial health disparities in the prevalence of AAS misuse as a function of sexual orientation. Prevention and intervention efforts are needed for sexual minority adolescent boys.
C1 [Blashill, Aaron J.; Safren, Steven A.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp,Fenway Inst, Boston, MA 02115 USA.
RP Blashill, AJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA.
EM ablashill@mgh.harvard.edu
FU Center for Population Research in LGBT Health at The Fenway Institute;
Eunice Kennedy Shriver National Institute of Child Health and Human
Development [R21HD051178]; National Institutes of Health (NIH)
FX Supported by The Center for Population Research in LGBT Health at The
Fenway Institute and by the Eunice Kennedy Shriver National Institute of
Child Health and Human Development under award R21HD051178. Investigator
time was supported by K23MH096647 (Dr Blashill) and K24MH094214 (Dr
Safren). Funded by the National Institutes of Health (NIH).
NR 42
TC 13
Z9 13
U1 3
U2 10
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD MAR
PY 2014
VL 133
IS 3
BP 469
EP 475
DI 10.1542/peds.2013-2768
PG 7
WC Pediatrics
SC Pediatrics
GA AG3PB
UT WOS:000335330700015
PM 24488735
ER
PT J
AU Lavelle, TA
Weinstein, MC
Newhouse, JP
Munir, K
Kuhlthau, KA
Prosser, LA
AF Lavelle, Tara A.
Weinstein, Milton C.
Newhouse, Joseph P.
Munir, Kerim
Kuhlthau, Karen A.
Prosser, Lisa A.
TI Economic Burden of Childhood Autism Spectrum Disorders
SO PEDIATRICS
LA English
DT Article
DE cost of illness; health economics; autism spectrum disorder
ID HEALTH-CARE EXPENDITURES; CHILDREN; COSTS; SERVICES; DIAGNOSIS;
MEDICAID; PROFILE; IMPACT; US
AB OBJECTIVE:To estimate the associations between autism spectrum disorder (ASD) diagnoses and service use, caregiver time, and cost outcomes.METHODS:We used national data from the Medical Expenditure Panel Survey linked to the National Health Interview Survey and a study-specific survey to estimate the annual utilization and costs for health care, school, ASD-related therapy, family-coordinated services, as well as caregiver time in children aged 3 to 17 years, with and without parent-reported ASD. Regression analyses estimated the association between ASD diagnosis and cost, controlling for child gender, age, race/ethnicity, insurance status, household income, country region and urban/rural classification, and non-ASD-related illnesses.RESULTS:Children with parent-reported ASD had higher levels of health care office visits and prescription drug use compared with children without ASD (P < .05). A greater proportion of children in the ASD group used special educational services (76% vs 7% in the control group, P < .05). After adjusting for child demographic characteristics and non-ASD-associated illnesses, ASD was associated with $3020 (95% confidence interval [CI]: $1017-$4259) higher health care costs and $14061 (95% CI: $4390-$24302) higher aggregate non-health care costs, including $8610 (95% CI: $6595-$10421) higher school costs. In adjusted analyses, parents who reported that their child had ASD did not have significantly higher out-of-pocket costs or spend more time on caregiving activities compared with control parents.CONCLUSIONS:The economic burden associated with ASD is substantial and can be measured across multiple sectors of our society. Previous analyses that focused on health care underestimated this economic burden, particularly for school systems.
C1 [Lavelle, Tara A.] Harvard Univ, PhD Program Hlth Policy, Cambridge, MA 02138 USA.
[Weinstein, Milton C.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
[Newhouse, Joseph P.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Munir, Kerim] Boston Childrens Hosp, Div Dev Med, Boston, MA USA.
[Kuhlthau, Karen A.] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA 02114 USA.
[Prosser, Lisa A.] Univ Michigan Hlth Syst, Div Gen Pediat, Child Hlth Evaluat & Res Unit, Ann Arbor, MI USA.
RP Lavelle, TA (reprint author), RAND Corp, 1200 South Hayes St, Arlington, VA 22202 USA.
EM tlavelle@rand.org
RI Munir, Kerim/D-6910-2015
OI Munir, Kerim/0000-0002-2404-1806
FU National Institute of Mental Health [5T32MH019733-18]; Harvard
University's Center for American Political Studies; National Institute
of Mental Health Research Training Program in Mental Health and
Developmental Disabilities at Boston Children's Hospital [R25 MH071286];
National Institute for Nursing Research [7-R01-NR-011880-03]; Harvard
University Graduate School of Arts and Sciences; Nancy Lurie Marks
Foundation
FX Funding for this study was provided by the National Institute of Mental
Health (5T32MH019733-18), Harvard University's Center for American
Political Studies, the National Institute of Mental Health Research
Training Program in Mental Health and Developmental Disabilities at
Boston Children's Hospital (R25 MH071286), National Institute for
Nursing Research (7-R01-NR-011880-03), Harvard University Graduate
School of Arts and Sciences, and the Nancy Lurie Marks Foundation.
NR 48
TC 34
Z9 34
U1 7
U2 26
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD MAR
PY 2014
VL 133
IS 3
BP E520
EP E529
DI 10.1542/peds.2013-0763
PG 10
WC Pediatrics
SC Pediatrics
GA AG3PB
UT WOS:000335330700025
PM 24515505
ER
PT J
AU Vacas-Jacques, P
Linnes, J
Young, A
Gerrard, V
Gomez-Marquez, J
AF Vacas-Jacques, Paulino
Linnes, Jacqueline
Young, Anna
Gerrard, Victoria
Gomez-Marquez, Jose
TI Portable digital lock-in instrument to determine chemical constituents
with single-color absorption measurements for Global Health Initiatives
SO REVIEW OF SCIENTIFIC INSTRUMENTS
LA English
DT Article
ID LOW-COST
AB Innovations in international health require the use of state-of-the-art technology to enable clinical chemistry for diagnostics of bodily fluids. We propose the implementation of a portable and affordable lock-in amplifier-based instrument that employs digital technology to perform biochemical diagnostics on blood, urine, and other fluids. The digital instrument is composed of light source and optoelectronic sensor, lock-in detection electronics, microcontroller unit, and user interface components working with either power supply or batteries. The instrument performs lock-in detection provided that three conditions are met. First, the optoelectronic signal of interest needs be encoded in the envelope of an amplitude-modulated waveform. Second, the reference signal required in the demodulation channel has to be frequency and phase locked with respect to the optoelectronic carrier signal. Third, the reference signal should be conditioned appropriately. We present three approaches to condition the signal appropriately: high-pass filtering the reference signal, precise offset tuning the reference level by low-pass filtering, and by using a voltage divider network. We assess the performance of the lock-in instrument by comparing it to a benchmark device and by determining protein concentration with single-color absorption measurements. We validate the concentration values obtained with the proposed instrument using chemical concentration measurements. Finally, we demonstrate that accurate retrieval of phase information can be achieved by using the same instrument. (C) 2014 AIP Publishing LLC.
C1 [Vacas-Jacques, Paulino; Linnes, Jacqueline; Young, Anna; Gerrard, Victoria; Gomez-Marquez, Jose] SUTD MIT Int Design Ctr, Little Devices Grp, Cambridge, MA 02139 USA.
[Vacas-Jacques, Paulino] Wellman Ctr Photomed, Boston, MA 02114 USA.
[Vacas-Jacques, Paulino] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
[Linnes, Jacqueline] Boston Univ, Biomed Engn Dept, Boston, MA 02215 USA.
[Gerrard, Victoria] Singapore Univ Technol & Design, Opportun Lab, Singapore 138682, Singapore.
RP Vacas-Jacques, P (reprint author), SUTD MIT Int Design Ctr, Little Devices Grp, Cambridge, MA 02139 USA.
RI Linnes, Jacqueline/D-3964-2016
OI Linnes, Jacqueline/0000-0003-4962-0908
NR 16
TC 1
Z9 1
U1 0
U2 10
PU AMER INST PHYSICS
PI MELVILLE
PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA
SN 0034-6748
EI 1089-7623
J9 REV SCI INSTRUM
JI Rev. Sci. Instrum.
PD MAR
PY 2014
VL 85
IS 3
AR 033103
DI 10.1063/1.4867097
PG 7
WC Instruments & Instrumentation; Physics, Applied
SC Instruments & Instrumentation; Physics
GA AH1ZL
UT WOS:000335920400004
PM 24689560
ER
PT J
AU Pessler, F
Ogdie, AR
Mayer, CT
Kretzschmar, WW
Dai, L
Elsaman, AM
Einhorn, E
Krenn, V
Schumacher, HR
AF Pessler, Frank
Ogdie, Alexis R.
Mayer, Christian T.
Kretzschmar, Warren W.
Dai, Lie
Elsaman, Ahmed M.
Einhorn, Eugene
Krenn, Veit
Schumacher, H. Ralph
TI Amyloid arthropathy associated with multiple myeloma: polyarthritis
without synovial infiltration of CD20+or CD38+cells
SO AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
LA English
DT Article
DE Amyloidosis; arthritis; B cells; multiple myeloma; plasma cells;
synovitis
ID WAR-VETERANS-ILLNESS; JOINT PAIN; DISEASE; ARTHRITIS
AB Objectives: To describe histological, immunohistochemical and ultrastructural features of synovial biopsies of amyloid arthropathy associated with multiple myeloma (MM). Methods: Synovial biopsies from affected joints of two patients with MM and amyloid arthropathy were examined with light and electron microscopy, and immunohistochemically for expression of CD3, CD8, CD20, CD38, CD68, Ki-67 and vWF.
Results were compared to values from osteoarthritis (OA, n=26), rheumatoid arthritis (RA, n=24) and normal (n=15) synovial membranes. Results: There was no or only mild lining hyperplasia. Vascular density was not elevated, and there were few Ki-67+ proliferating cells in the stroma. The Krenn synovitis score classified one specimen as "low-grade'' and one as "high-grade'' synovitis. CD68+ and CD3+ cells were the predominant mononuclear inflammatory cells, whereas CD20+ and CD38+ cells were absent from both synovial membrane and synovial fluid sediment. Electron microscopy demonstrated amyloid phagocytosis by synovial macrophages. In hierarchical clustering the two amyloid arthropathy specimens were more closely related to OA than to RA or normal synovium.
Conclusions: This first detailed immunohistological analysis of MM-associated amyloid arthropathy suggests that it is a chronic synovitis that evolves despite the loss of humoral immunity seen in advanced MM. Instead, amyloid phagocytosis by synovial macrophages likely triggers and perpetuates local disease.
C1 [Pessler, Frank; Mayer, Christian T.] TWINCORE Ctr Expt & Clin Infect Res, D-30625 Hannover, Germany.
[Pessler, Frank; Elsaman, Ahmed M.] Helmholtz Ctr Infect Res, Braunschweig, Germany.
[Ogdie, Alexis R.; Dai, Lie; Schumacher, H. Ralph] Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA.
[Kretzschmar, Warren W.] Wellcome Trust Ctr Human Genet, Oxford, England.
[Dai, Lie] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Rheumatol, Guangzhou 510275, Guangdong, Peoples R China.
[Elsaman, Ahmed M.] Sohag Univ, Dept Rheumatol & Rehabil, Sohag, Egypt.
[Einhorn, Eugene] Philadelphia VA Med Ctr, Dept Pathol, Philadelphia, PA USA.
[Krenn, Veit] Ctr Histol Cytol & Mol Diagnost, Trier, Germany.
[Schumacher, H. Ralph] Philadelphia VA Med Ctr, Div Rheumatol, Philadelphia, PA USA.
RP Pessler, F (reprint author), TWINCORE Ctr Expt & Clin Infect Res, Feodor Lynen Str 7-9, D-30625 Hannover, Germany.
EM frank.pessler@twincore.de
OI Kretzschmar, Warren/0000-0002-2575-0807; Ogdie,
Alexis/0000-0002-4639-0775
FU American College of Rheumatology/Research; Education Foundation Health
Professional Graduate Student Research Preceptorship award; Wellcome
Trust [09730/Z/11/Z]; German-Egyptian Scientific Projects (GESP) from
the German Academic Exchange Service (DAAD) [51309219]; Ministry of
Higher Education and Scientific Research of the Arab Republic of Egypt;
Helmholtz Association
FX C. T. Mayer was supported by an American College of
Rheumatology/Research and Education Foundation Health Professional
Graduate Student Research Preceptorship award. WWK is supported by a
Wellcome Trust studentship (09730/Z/11/Z). AME was supported by
German-Egyptian Scientific Projects (GESP) grant no. 51309219 from the
German Academic Exchange Service (DAAD) and the Ministry of Higher
Education and Scientific Research of the Arab Republic of Egypt. The
study was supported in part by funds from the Helmholtz Association
(Programs in Infection and Immunity and in Individualized Medicine,
iMed). The study was approved by the Institutional Review Board of the
Philadelphia VA Medical Center as part of a larger study of synovial
histopathology. The need to obtain informed consent was waived due to
the use of anonymized data.
NR 21
TC 1
Z9 2
U1 0
U2 1
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1350-6129
EI 1744-2818
J9 AMYLOID
JI Amyloid-J. Protein Fold. Disord.
PD MAR
PY 2014
VL 21
IS 1
BP 28
EP 34
DI 10.3109/13506129.2013.862229
PG 7
WC Biochemistry & Molecular Biology; Medicine, General & Internal;
Medicine, Research & Experimental
SC Biochemistry & Molecular Biology; General & Internal Medicine; Research
& Experimental Medicine
GA AG9UB
UT WOS:000335764200005
PM 24286442
ER
PT J
AU Tan, ASL
Gibson, L
Zafar, HM
Gray, SW
Hornik, RC
Armstrong, K
AF Tan, Andy S. L.
Gibson, Laura
Zafar, Hanna M.
Gray, Stacy W.
Hornik, Robert C.
Armstrong, Katrina
TI Associations between Cancer-Related Information Seeking and Receiving
PET Imaging for Routine Cancer Surveillance-An Analysis of Longitudinal
Survey Data
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; BREAST-CANCER; MAXIMUM-LIKELIHOOD;
COLORECTAL-CANCER; MISSING DATA; CLINICAL-ONCOLOGY; AMERICAN-SOCIETY;
FOLLOW-UP; FDG PET; CARE
AB Background: Routine cancer surveillance with positron emission tomography (PET) is not recommended for most patients who have completed curative treatment for cancer. Yet, recent trends suggest that PET is increasingly used for follow-up among patients with cancer. This study investigates whether informationseeking behaviors predicted self-reported utilization of PET for routine surveillance in patients with colorectal, breast, and prostate cancer.
Methods: We conducted annual surveys for 3 years in a cohort of Pennsylvania cancer survivors diagnosed with colorectal, breast, or prostate cancer in 2005. The outcome was self-reported PET receipt for routine surveillance among 944 patients diagnosed with nonmetastatic disease (stages 0-III). Predictors included cancer-related information seeking from nonmedical sources and providers. Weighted multiple logistic regression analyses were performed.
Results: In this population, 11% of patients reported receiving at least one PET scan for routine follow-up in a 12-month period several years after diagnosis. Seeking cancer-related information from nonmedical sources was associated with higher odds of subsequent reported PET use [OR, 3.7; 95% confidence interval (CI), 1.112.1; P 0.032], after adjusting for potential confounders. Patient engagement with physicians about cancerrelated information was not a significant predictor.
Conclusions: Overall reported PET utilization for routine surveillance of colorectal, breast, and prostate cancer is low. However, we found a significant association with information seeking from nonmedical sources but not from providers. Impact: Exposure to cancer-related information through mass media and lay interpersonal sources may be driving inappropriate utilization of high-cost advanced imaging procedures. These findings have important implications for cancer survivors, healthcare providers, and health policy.
C1 [Tan, Andy S. L.; Gibson, Laura; Hornik, Robert C.] Univ Penn, Annenberg Sch Commun, Ctr Excellence Canc Commun Res, Philadelphia, PA 19104 USA.
[Zafar, Hanna M.] Hosp Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA.
[Gray, Stacy W.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Ctr Community Based Res, Boston, MA 02115 USA.
[Armstrong, Katrina] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
RP Tan, ASL (reprint author), Univ Penn, Annenberg Sch Commun, 3620 Walnut St, Philadelphia, PA 19104 USA.
EM andytan@alumni.upenn.edu
OI Tan, Andy/0000-0001-6459-6171; Hornik, Robert/0000-0002-2148-8805
FU National Cancer Institute [P50CA095856, P20CA095856]; L.Gibson
[P20CA095856]
FX This work was supported by the National Cancer Institute grant nos.
P50CA095856 (to R.C.Hornik) and P20CA095856 (to R.C.Hornik and
K.Armstrong).A.S.L.Tan and L.Gibson were supported for this work by
P20CA095856.; The costs of publication of this article were defrayed in
part by the payment of page charges.This article must therefore be
hereby marked advertisement in accordance with 18 U.S.C.Section 1734
solely to indicate this fact.
NR 49
TC 1
Z9 1
U1 1
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD MAR
PY 2014
VL 23
IS 3
BP 481
EP 489
DI 10.1158/1055-9965.EPI-13-0999
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA AG0ZO
UT WOS:000335144700014
PM 24550351
ER
PT J
AU Buys, E
Sips, P
AF Buys, Emmanuel
Sips, Patrick
TI New insights into the role of soluble guanylate cyclase in blood
pressure regulation
SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION
LA English
DT Review
DE hypertension; soluble guanylate cyclase; nitric oxide; redox;
vasodilation
ID PULMONARY ARTERIAL-HYPERTENSION; CYCLIC GUANOSINE-MONOPHOSPHATE; H-NOX
DOMAIN; NITRIC-OXIDE; CARBON-MONOXIDE; ENDOTHELIAL DYSFUNCTION;
S-NITROSYLATION; TUBULOGLOMERULAR FEEDBACK; CARDIOVASCULAR-RESPONSES;
NITROSATIVE STRESS
AB Purpose of review
Nitric oxide (NO)-soluble guanylate cyclase (sGC)-dependent signaling mechanisms have a profound effect on the regulation of blood pressure (BP). In this review, we will discuss recent findings in the field that support the importance of sGC in the development of hypertension.
Recent findings
The importance of sGC in BP regulation was highlighted by studies using genetically modified animal models, chemical stimulators/activators and inhibitors of the NO/sGC signaling pathway, and genetic association studies in humans. Many studies further support the role of NO/sGC in vasodilation and vascular dysfunction, which is underscored by the early clinical success of synthetic sGC stimulators for the treatment of pulmonary hypertension. Recent work has uncovered more details about the structural basis of sGC activation, enabling the development of more potent and efficient modulators of sGC activity. Finally, the mechanisms involved in the modulation of sGC by signaling gases other than NO, as well as the influence of redox signaling on sGC, have been the subject of several interesting studies.
sGC is fast becoming an interesting therapeutic target for the treatment of vascular dysfunction and hypertension, with novel sGC stimulating/activating compounds as promising clinical treatment options.
C1 [Buys, Emmanuel] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA.
[Sips, Patrick] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med, Boston, MA 02115 USA.
RP Sips, P (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, 75 Francis St,Thorn 1123, Boston, MA 02115 USA.
EM psips@partners.org
OI Sips, Patrick/0000-0001-9241-5980
FU NIH [R01 EY022746-01, R01 HL113933-01A1, R01-HL110378-01A1, U54
NS079201-02]; American Heart Association [10SDG2610313]
FX E.B. was supported by NIH grants R01 EY022746-01, R01 HL113933-01A1, and
R01-HL110378-01A1, and by a Scientist Development Grant from the
American Heart Association 10SDG2610313. P. S. received support from NIH
grant U54 NS079201-02.
NR 73
TC 6
Z9 7
U1 1
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1062-4821
EI 1473-6543
J9 CURR OPIN NEPHROL HY
JI Curr. Opin. Nephrol. Hypertens.
PD MAR
PY 2014
VL 23
IS 2
BP 135
EP 142
DI 10.1097/01.mnh.0000441048.91041.3a
PG 8
WC Urology & Nephrology; Peripheral Vascular Disease
SC Urology & Nephrology; Cardiovascular System & Cardiology
GA AG1FF
UT WOS:000335159800007
PM 24419369
ER
PT J
AU Belayev, LY
Palevsky, PM
AF Belayev, Linda Y.
Palevsky, Paul M.
TI The link between acute kidney injury and chronic kidney disease
SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION
LA English
DT Review
DE chronic kidney disease; epidemiology; acute kidney injury
ID ACUTE-RENAL-FAILURE; ACUTE TUBULAR-NECROSIS; CHRONIC DIALYSIS;
FOLLOW-UP; RISK; PROGRESSION; DEATH; OUTCOMES; INCREASES; FIBROSIS
AB Purpose of review
It has been argued that the existing epidemiologic data are insufficient to establish a causal link between acute kidney injury (AKI) and subsequent development or progression of chronic kidney disease (CKD), especially given that risk factors for the development of AKI overlap with those for progressive CKD.
Recent findings
Multiple studies published over the past 5 years have demonstrated a strong epidemiologic association between episodes of AKI and subsequent development or progression of CKD, including evidence that severity of AKI and repeated episodes of AKI are associated with increased risk of CKD. In addition, animal models have provided evidence for a biological basis linking episodes of AKI with CKD.
The preponderance of data support a causal link between episodes of AKI and subsequent development or progression of CKD.
C1 [Belayev, Linda Y.; Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA USA.
[Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA.
RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Room 7E123 111F U,Univ Dr, Pittsburgh, PA 15240 USA.
EM Palevsky@pitt.edu
OI Palevsky, Paul/0000-0002-7334-5400
FU NIDDK NIH HHS [T32 DK061296]
NR 35
TC 17
Z9 18
U1 3
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1062-4821
EI 1473-6543
J9 CURR OPIN NEPHROL HY
JI Curr. Opin. Nephrol. Hypertens.
PD MAR
PY 2014
VL 23
IS 2
BP 149
EP 154
DI 10.1097/01.mnh.0000441051.36783.f3
PG 6
WC Urology & Nephrology; Peripheral Vascular Disease
SC Urology & Nephrology; Cardiovascular System & Cardiology
GA AG1FF
UT WOS:000335159800009
PM 24384553
ER
PT J
AU Bhan, I
AF Bhan, Ishir
TI Phosphate management in chronic kidney disease
SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION
LA English
DT Review
DE phosphate binders; hyperphosphatemia; mineral and bone disease; chronic
kidney disease
ID CALCIUM ACETATE/MAGNESIUM CARBONATE; INCIDENT HEMODIALYSIS-PATIENTS;
RANDOMIZED CLINICAL-TRIAL; STAGE RENAL-DISEASE; MAINTENANCE
HEMODIALYSIS; SEVELAMER-HYDROCHLORIDE; LANTHANUM CARBONATE; PHOSPHORUS
BINDERS; SERUM PHOSPHATE; HYPERPHOSPHATEMIA
AB Purpose of review
The review focuses on the rationale and evidence behind management strategies for hyperphosphatemia in patients with chronic kidney disease (CKD).
Recent findings
Optimal management of phosphate in CKD remains an area of uncertainty, but multiple studies now point to a clinical benefit from the use of phosphate binders. Evidence of improved survival is particularly strong with sevelamer, though it remains unclear whether the absence of calcium or other properties of sevelamer are responsible for this relationship. Newer agents, such as iron-based binders or niacin compounds to inhibit phosphorus absorption, may have additional benefits which will be better defined with additional experience. A reduced pill count may be a particularly beneficial characteristic of newer agents, and has been associated with improved response to therapy. Increased use of frequent, nocturnal hemodialysis is an additional tool to help ameliorate phosphate control. Data on the reduction of fibroblast growth factor 23 through use of phosphate binders remain weak.
An improved understanding of phosphate regulation and the development of new therapeutic agents have reinvigorated a once stagnant field, but significant changes to practice cannot yet be justified. There is increasing support for using sevelamer in place of calcium-based binders, though economic practicability remains challenging.
C1 [Bhan, Ishir] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA.
RP Bhan, I (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
NR 39
TC 2
Z9 2
U1 0
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1062-4821
EI 1473-6543
J9 CURR OPIN NEPHROL HY
JI Curr. Opin. Nephrol. Hypertens.
PD MAR
PY 2014
VL 23
IS 2
BP 174
EP 179
DI 10.1097/01.mnh.0000441155.47696.41
PG 6
WC Urology & Nephrology; Peripheral Vascular Disease
SC Urology & Nephrology; Cardiovascular System & Cardiology
GA AG1FF
UT WOS:000335159800013
PM 24445424
ER
PT J
AU Naylor, MG
Cardenas, VA
Tosun, D
Schuff, N
Weiner, M
Schwartzman, A
AF Naylor, Melissa G.
Cardenas, Valerie A.
Tosun, Duygu
Schuff, Norbert
Weiner, Michael
Schwartzman, Armin
TI Voxelwise multivariate analysis of multimodality magnetic resonance
imaging
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE multiple comparisons; diffusion tensor imaging; structural magnetic
resonance imaging; multivariate analysis; Alzheimer's disease; perfusion
weighted magnetic resonance imaging; multimodality imaging
ID CANONICAL CORRELATION-ANALYSIS; ALZHEIMERS-DISEASE; REGRESSION
AB Most brain magnetic resonance imaging (MRI) studies concentrate on a single MRI contrast or modality, frequently structural MRI. By performing an integrated analysis of several modalities, such as structural, perfusion-weighted, and diffusion-weighted MRI, new insights may be attained to better understand the underlying processes of brain diseases. We compare two voxelwise approaches: (1) fitting multiple univariate models, one for each outcome and then adjusting for multiple comparisons among the outcomes and (2) fitting a multivariate model. In both cases, adjustment for multiple comparisons is performed over all voxels jointly to account for the search over the brain. The multivariate model is able to account for the multiple comparisons over outcomes without assuming independence because the covariance structure between modalities is estimated. Simulations show that the multivariate approach is more powerful when the outcomes are correlated and, even when the outcomes are independent, the multivariate approach is just as powerful or more powerful when at least two outcomes are dependent on predictors in the model. However, multiple univariate regressions with Bonferroni correction remain a desirable alternative in some circumstances. To illustrate the power of each approach, we analyze a case control study of Alzheimer's disease, in which data from three MRI modalities are available. Hum Brain Mapp 35:831-846, 2014. (c) 2013 Wiley Periodicals, Inc.
C1 [Naylor, Melissa G.; Schwartzman, Armin] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Naylor, Melissa G.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA.
[Cardenas, Valerie A.; Tosun, Duygu; Schuff, Norbert; Weiner, Michael] Dept Vet Affairs Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA.
[Cardenas, Valerie A.; Tosun, Duygu; Schuff, Norbert; Weiner, Michael] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA.
[Schwartzman, Armin] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
RP Naylor, MG (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
EM mgn@uchicago.edu
OI Schwartzman, Armin/0000-0001-5335-1611
FU National Institute of Health [T32 MH017119, U01 HL089856, R01 MH081862,
R01 MH087590, R21EB013795, R01 CA157528]; NIH [R03EB008136, P41EB015904,
P50AG023501, P01AG19724]
FX Contract grant sponsor: National Institute of Health; Contract grant
numbers: T32 MH017119, U01 HL089856, R01 MH081862, R01 MH087590,
R21EB013795, and R01 CA157528; Contract grant sponsor: NIH, administered
by the Northern California Institute for Research and Education, with
resources of the Veterans Affairs Medical Center, San Francisco,
California; Contract grant numbers: R03EB008136, P41EB015904,
P50AG023501, and P01AG19724.
NR 25
TC 5
Z9 5
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1065-9471
EI 1097-0193
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD MAR
PY 2014
VL 35
IS 3
BP 831
EP 846
DI 10.1002/hbm.22217
PG 16
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA AF0IW
UT WOS:000334398500008
PM 23408378
ER
PT J
AU Ward, AM
Schultz, AP
Huijbers, W
Van Dijk, KRA
Hedden, T
Sperling, RA
AF Ward, Andrew M.
Schultz, Aaron P.
Huijbers, Willem
Van Dijk, Koene R. A.
Hedden, Trey
Sperling, Reisa A.
TI The parahippocampal gyrus links the default-mode cortical network with
the medial temporal lobe memory system
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE brain networks; functional connectivity; human; Magnetic Resonance
Imaging; young adult; brain mapping; resting state; physiology; MTL;
Mediation
ID INTRINSIC FUNCTIONAL CONNECTIVITY; RESTING-STATE NETWORKS; INDEPENDENT
COMPONENT ANALYSIS; MILD COGNITIVE IMPAIRMENT; FALSE DISCOVERY RATE;
ALZHEIMERS-DISEASE; HUMAN BRAIN; RECOGNITION MEMORY;
HIPPOCAMPAL-FORMATION; SENSORY STIMULATION
AB The default-mode network (DMN) is a distributed functional-anatomic network implicated in supporting memory. Current resting-state functional connectivity studies in humans remain divided on the exact involvement of medial temporal lobe (MTL) in this network at rest. Notably, it is unclear to what extent the MTL regions involved in successful memory encoding are connected to the cortical nodes of the DMN during resting state. Our findings using functional connectivity MRI analyses of resting-state data indicate that the parahippocampal gyrus (PHG) is the primary hub of the DMN in the MTL during resting state. Also, connectivity of the PHG is distinct from connectivity of hippocampal regions identified by an associative memory-encoding task. We confirmed that several hippocampal encoding regions lack significant functional connectivity with cortical DMN nodes during resting state. Additionally, a mediation analysis showed that resting-state connectivity between the hippocampus and posterior cingulate cortex-a major hub of the DMN-is indirect and mediated by the PHG. Our findings support the hypothesis that the MTL memory system represents a functional subnetwork that relates to the cortical nodes of the DMN through parahippocampal functional connections. Hum Brain Mapp 35:1061-1073, 2014. (c) 2013 Wiley Periodicals, Inc.
C1 [Ward, Andrew M.; Huijbers, Willem; Sperling, Reisa A.] Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Ward, Andrew M.; Schultz, Aaron P.; Huijbers, Willem; Sperling, Reisa A.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Ward, Andrew M.; Schultz, Aaron P.; Huijbers, Willem; Van Dijk, Koene R. A.; Hedden, Trey; Sperling, Reisa A.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Van Dijk, Koene R. A.; Hedden, Trey] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Van Dijk, Koene R. A.] Harvard Univ, Dept Psychol, Ctr Brain Sci, Cambridge, MA 02138 USA.
[Sperling, Reisa A.] Ctr Alzheimer Res & Treatment, Boston, MA USA.
RP Sperling, RA (reprint author), Sperling, 221 Longwood Ave, Boston, MA 02115 USA.
EM rsperling@rics.bwh.harvard.edu
RI Van Dijk, Koene/G-3317-2012;
OI Van Dijk, Koene/0000-0001-6137-4282; Ward, Andrew/0000-0001-6948-4814
FU NIA [AG027435, P01AG036694, P50 AG005134, K24 AG035007, NS002189, K01
AG040197]; European Molecular Biology Organization [ALTF 318-2011];
Fidelity Medical Foundation; Harvard NeuroDiscovery Center; American
Health Assistance Foundation
FX Contract grant sponsor: NIA; Contract grant numbers: AG027435,
P01AG036694, P50 AG005134, K24 AG035007, NS002189, K01 AG040197;
Contract grant sponsor: the European Molecular Biology Organization;
Contract grant number: ALTF 318-2011 ( W. H.); Contract grant sponsor:
the Fidelity Medical Foundation; the Harvard NeuroDiscovery Center; and
the American Health Assistance Foundation.
NR 104
TC 49
Z9 49
U1 1
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1065-9471
EI 1097-0193
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD MAR
PY 2014
VL 35
IS 3
BP 1061
EP 1073
DI 10.1002/hbm.22234
PG 13
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA AF0IW
UT WOS:000334398500025
PM 23404748
ER
PT J
AU Leritz, EC
Shepel, J
Williams, VJ
Lipsitz, LA
McGlinchey, RE
Milberg, WP
Salat, DH
AF Leritz, Elizabeth C.
Shepel, Juli
Williams, Victoria J.
Lipsitz, Lewis A.
McGlinchey, Regina E.
Milberg, William P.
Salat, David H.
TI Associations between T-1 white matter lesion volume and regional white
matter microstructure in aging
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE white matter lesions; diffusion tensor imaging; aging; white matter
microstructure
ID HUMAN CEREBRAL-CORTEX; MAGNETIC-RESONANCE IMAGES; SURFACE-BASED
ANALYSIS; DIFFUSION TENSOR MRI; HEALTHY OLDER-ADULTS;
MULTIPLE-SCLEROSIS; ALZHEIMERS-DISEASE; BLOOD-PRESSURE;
NEUROPSYCHOLOGICAL IMPAIRMENT; COGNITIVE IMPAIRMENT
AB White matter lesions, typically manifesting as regions of signal intensity abnormality (WMSA) on MRI, increase in frequency with age. However, the role of this damage in cognitive decline and disease is still not clear, as lesion volume has only loosely been associated with clinical status. Diffusion tensor imaging (DTI) has been used to examine the quantitative microstructural integrity of white matter, and has applications in the examination of subtle changes to tissue that appear visually normal on conventional imaging. The primary goal of this study was to determine whether major macrostructural white matter damage, (total WMSA volume), is associated with microstructural integrity of normal appearing white matter, and if these macrostructural changes fully account for microstructural changes. Imaging was performed in 126 nondemented individuals, ages 43-85 years, with no history of cerebrovascular disease. Controlling for age, greater WMSA volume was associated with decreased fractional anisotropy (FA) in widespread brain regions. Patterns were similar for FA and radial diffusivity but in contrast, WMSA was associated with axial diffusivity in fewer areas. Age was associated with FA in several regions, and many of these effects remained even when controlling for WMSA volume, suggesting the etiology of WMSAs does not fully account for all age-associated white matter deterioration. These results provide evidence that WMSA volume is associated with the integrity of normal-appearing white matter. In addition, our results suggest that overt lesions may not account for the association of increasing age with decreased white matter tissue integrity. Hum Brain Mapp 35:1085-1100, 2014. (c) 2013 Wiley Periodicals, Inc.
C1 [Leritz, Elizabeth C.; Shepel, Juli; Williams, Victoria J.; McGlinchey, Regina E.; Milberg, William P.; Salat, David H.] VA Boston Healthcare Syst, GRECC, Boston, MA USA.
[Leritz, Elizabeth C.; Shepel, Juli; Williams, Victoria J.; McGlinchey, Regina E.; Milberg, William P.; Salat, David H.] VA Boston Healthcare Syst, Neuroimaging Res Vet Ctr NeRVe, Boston, MA USA.
[Leritz, Elizabeth C.; Shepel, Juli; Williams, Victoria J.; McGlinchey, Regina E.; Milberg, William P.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA.
[Leritz, Elizabeth C.; McGlinchey, Regina E.; Milberg, William P.; Salat, David H.] Harvard Univ, Sch Med, Boston, MA USA.
[Leritz, Elizabeth C.; Shepel, Juli; Williams, Victoria J.; Salat, David H.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
[Lipsitz, Lewis A.] Beth Israel Deaconness Med Ctr, Boston, MA USA.
RP Leritz, EC (reprint author), 150 South Huntington Ave,GRECC 182 JP, Boston, MA 02130 USA.
EM bleritz@nmr.mgh.harvard.edu
RI McGlinchey, Regina/R-1971-2016
FU National Institute of Neurologic Disorders and Stroke [K23NS062148];
National Institute of Nursing Research [R01NR010827]; National Institute
on Aging [P60AG08812, P01AG004390]; Medical Research Service VA
FX Contract grant sponsor: National Institute of Neurologic Disorders and
Stroke; Contract grant number: K23NS062148; Contract grant sponsor:
National Institute of Nursing Research; Contract grant number:
R01NR010827; Contract grant sponsor: National Institute on Aging;
Contract grant number: P60AG08812 and P01AG004390; Contract grant
sponsor: Medical Research Service VA (Merit Review Awards to W.M. and
R.McG.).
NR 93
TC 15
Z9 16
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1065-9471
EI 1097-0193
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD MAR
PY 2014
VL 35
IS 3
BP 1085
EP 1100
DI 10.1002/hbm.22236
PG 16
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA AF0IW
UT WOS:000334398500027
PM 23362153
ER
PT J
AU Chan, NK
Abdullah, KG
Lubelski, D
Steinmetz, MP
Benzel, EC
Shin, JH
Mroz, TE
AF Chan, N. K.
Abdullah, K. G.
Lubelski, D.
Steinmetz, M. P.
Benzel, E. C.
Shin, J. H.
Mroz, T. E.
TI Stereotactic radiosurgery for metastatic spine tumors
SO JOURNAL OF NEUROSURGICAL SCIENCES
LA English
DT Review
DE Spinal cord neoplasms, radiotherapy; Radiosurgery; Spinal neoplasms,
secondary; Spinal neoplasms, surgery
ID INTENSITY-MODULATED RADIOTHERAPY; ONCOLOGY STUDY-GROUP; CORD
COMPRESSION; BODY RADIOTHERAPY; CYBERKNIFE RADIOSURGERY;
CLINICAL-EXPERIENCE; RADIATION-THERAPY; PARASPINAL TUMORS;
SINGLE-SESSION; PAIN-CONTROL
AB Spinal metastases invariably affect the majority of patients with cancer. Many will develop symptoms related to pain and disability from epidural spinal cord compression as well as pathologic fracture of the vertebrae. With the emergence of targeted systemic therapies and a better understanding of cancer biology, patients are living longer with bony metastases. This poses particular challenges, as palliation of pain and maintenance of local tumor control are paramount to quality of life and overall functional independence for these patients. Stereotactic radiosurgery (SRS) has emerged as a potent primary standalone and adjuvant treatment option for spinal metastases. To date, the primary indications for SRS include 1) upfront standalone treatment for painful bony metastases in the oligometastatic patient, 2) standalone or post-operative treatment following progression or recurrence of local disease despite previous conventional external beam radiation therapy (cEBRT), and 3) following surgery during which epidural disease is decompressed and the spine stabilized when indicated. SRS has demonstrated a significant advantage over cEBRT for tumors traditionally regarded as relatively radioresistant such as sarcoma, melanoma, renal cell carcinoma, non-small cell lung cancer and colon carcinoma.9 The radiobiological advantage of increased tumoricidal dose delivery and spinal cord dose sparing in SRS have made this a powerful treatment alternative to cEBRT particularly within the context of re-irradiation. Given the limitations of spinal cord dose constraints, surgery is still the first-line therapy in patients with high-grade epidural spinal cord compression (ESCC). Epidural compression can be treated with SRS, however this risks radiation-induced myelopathy and challenges the safety of effective dose delivery at the du-ral margin.(11) With increasing dose, radiation-induced vertebral fracture is the most serious and prevalent side effect of SRS.(53) An overview of SRS, including the most common indications, complications, and outcomes for spinal metastases are presented here.
C1 [Chan, N. K.; Abdullah, K. G.; Lubelski, D.; Benzel, E. C.; Mroz, T. E.] Cleveland Clin, Ctr Spine Hlth, Cleveland, OH 44195 USA.
[Chan, N. K.; Abdullah, K. G.; Lubelski, D.; Benzel, E. C.; Mroz, T. E.] Cleveland Clin, Dept Neurol Surg, Cleveland, OH 44195 USA.
[Chan, N. K.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA.
[Abdullah, K. G.; Lubelski, D.; Benzel, E. C.; Mroz, T. E.] Cleveland Clin, Lerner Coll Med, Cleveland, OH 44195 USA.
[Abdullah, K. G.] MetroHlth Med Ctr, Dept Neurosurg, Cleveland, OH USA.
[Steinmetz, M. P.] Hosp Univ Penn, Dept Neurosurg, Philadelphia, PA 19104 USA.
[Shin, J. H.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
RP Mroz, TE (reprint author), Cleveland Clin, Dept Orthoped, Ctr Spine Hlth, 9500 Euclid Ave,S-40, Cleveland, OH 44195 USA.
EM mrozt@ccf.org
NR 53
TC 4
Z9 4
U1 1
U2 2
PU EDIZIONI MINERVA MEDICA
PI TURIN
PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY
SN 0390-5616
EI 1827-1855
J9 J NEUROSURG SCI
JI J. Neurosurg. Sci.
PD MAR
PY 2014
VL 58
IS 1
BP 37
EP 44
PG 8
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA AG4CK
UT WOS:000335366600006
PM 24614791
ER
PT J
AU Pagoto, SL
Schneider, KL
Oleski, J
Smith, B
Bauman, M
AF Pagoto, Sherry L.
Schneider, Kristin L.
Oleski, Jessica
Smith, Brian
Bauman, Michael
TI The Adoption and Spread of a Core-Strengthening Exercise Through an
Online Social Network
SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH
LA English
DT Article
DE Twitter; exercise; social networks
ID PHYSICAL-ACTIVITY; CONTROLLED-TRIAL; UNITED-STATES; PREVALENCE; SUPPORT;
ADULTS
AB Background: The present feasibility study describes engagement and spread of a Twitter-based core-strengthening challenge. Methods: A challenge that entailed completing a core-strengthening exercise using a hashtag (#PlankADay) was circulated via Twitter. This study surveyed users who joined during the first 2 months of the challenge to describe their characteristics, including social support for exercise and to what extent they invited others to join. The study continued to track total users for 10 months. Results: Of 407 individuals who joined in the first 2 months, 105 completed surveys. Among these, 81% were female and 86% white and mean age was 35.8. 72% participated for at least 1 month and 47% participated for at least 2 months. Survey participants reported that the challenge increased their enjoyment of abdominal exercise. Of the 68% of participants who invited others to participate, 28% recruited none, 66% recruited 1-5 users, and 6% recruited 10 or more users. Participants reported that online friends provided as much positive social support for exercise as family and in-person friends. In 14 months, 4941 users produced 76,746 tweets and mean total tweets per user was 15.86 (SD = 75.34; range = 1-2888). Conclusion: Online social networks may be a promising mechanism to spread brief exercise behaviors.
C1 [Pagoto, Sherry L.; Schneider, Kristin L.; Oleski, Jessica] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01655 USA.
[Smith, Brian] Boston Univ, Sch Med, Dept Med, VA Boston Healthcare Syst, Boston, MA 02118 USA.
[Bauman, Michael] MB Financial Grp, Macomb, MI USA.
RP Pagoto, SL (reprint author), Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01655 USA.
NR 14
TC 8
Z9 8
U1 1
U2 10
PU HUMAN KINETICS PUBL INC
PI CHAMPAIGN
PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA
SN 1543-3080
EI 1543-5474
J9 J PHYS ACT HEALTH
JI J. Phys. Act. Health
PD MAR
PY 2014
VL 11
IS 3
BP 648
EP 653
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AF8RQ
UT WOS:000334983700024
PM 23416874
ER
PT J
AU Rosen, AK
Chen, Q
Shin, MH
O'Brien, W
Shwartz, M
Mull, HJ
Cevasco, M
Borzecki, AM
AF Rosen, Amy K.
Chen, Qi
Shin, Marlena H.
O'Brien, William
Shwartz, Michael
Mull, Hillary J.
Cevasco, Marisa
Borzecki, Ann M.
TI Medical and Surgical Readmissions in the Veterans Health Administration
What Proportion are Related to the Index Hospitalization?
SO MEDICAL CARE
LA English
DT Article
DE readmission; quality of care; unplanned readmission; clinically related
readmission; quality improvement
ID QUALITY-OF-CARE; FEE-FOR-SERVICE; COLORECTAL SURGERY; PATIENT SAFETY;
HEART-FAILURE; RISK-FACTORS; RATES; PROGRAM; ASSOCIATION; MORTALITY
AB Background:
Readmissions are an attractive quality measure because they offer a broad view of quality beyond the index hospitalization. However, the extent to which medical or surgical readmissions reflect quality of care is largely unknown, because of the complexity of factors related to readmission. Identifying those readmissions that are clinically related to the index hospitalization is an important first step in closing this knowledge gap.
Objectives:
The aims of this study were to examine unplanned readmissions in the Veterans Health Administration, identify clinically related versus unrelated unplanned readmissions, and compare the leading reasons for unplanned readmission between medical and surgical discharges.
Methods:
We classified 2,069,804 Veterans Health Administration hospital discharges (Fiscal Years 2003-2007) into medical/surgical index discharges with/without readmissions per their diagnosis-related groups. Our outcome variable was "all-cause" 30-day unplanned readmission. We compared medical and surgical unplanned readmissions (n=217,767) on demographics, clinical characteristics, and readmission reasons using descriptive statistics.
Results:
Among all unplanned readmissions, 41.5% were identified as clinically related. Not surprisingly, heart failure (10.2%) and chronic obstructive pulmonary disease (6.5%) were the top 2 reasons for clinically related readmissions among medical discharges; postoperative complications (ie, complications of surgical procedures and medical care or complications of devices) accounted for 70.5% of clinically related readmissions among surgical discharges.
Conclusions:
Although almost 42% of unplanned readmissions were identified as clinically related, the majority of unplanned readmissions were unrelated to the index hospitalization. Quality improvement interventions targeted at processes of care associated with the index hospitalization are likely to be most effective in reducing clinically related readmissions. It is less clear how to reduce nonclinically related readmissions; these may involve broader factors than inpatient care.
C1 [Rosen, Amy K.; Chen, Qi; Shin, Marlena H.; O'Brien, William; Shwartz, Michael; Mull, Hillary J.; Borzecki, Ann M.] Boston Univ, Sch Med, Ctr Healthcare Org & Implementat Res CHOIR, Boston, MA 02118 USA.
[Rosen, Amy K.; Mull, Hillary J.] Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA.
[Shwartz, Michael] Boston Univ, Sch Management, Dept Operat & Technol Management, Boston, MA 02215 USA.
[Cevasco, Marisa] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
[Borzecki, Ann M.] Ctr Healthcare Org & Implementat Res CHOIR, Bedford, MA USA.
[Borzecki, Ann M.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA.
[Borzecki, Ann M.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02215 USA.
RP Rosen, AK (reprint author), VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, 150 S Huntington Ave 152 M, Boston, MA 02130 USA.
EM akrosen@bu.edu
FU Department of Veterans Affairs, Veterans Health Administration, Health
Services Research and Development, SDR [07-002]
FX Supported by the Department of Veterans Affairs, Veterans Health
Administration, Health Services Research and Development, SDR #07-002.
NR 42
TC 7
Z9 7
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0025-7079
EI 1537-1948
J9 MED CARE
JI Med. Care
PD MAR
PY 2014
VL 52
IS 3
BP 243
EP 249
DI 10.1097/MLR.0000000000000081
PG 7
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA AG3NW
UT WOS:000335327400010
PM 24374424
ER
PT J
AU Lamont, EB
Lan, L
AF Lamont, Elizabeth B.
Lan, Lan
TI Sensitivity of Medicare Claims Data for Measuring Use of Standard
Multiagent Chemotherapy Regimens
SO MEDICAL CARE
LA English
DT Article
DE comparative effectiveness research; elderly; chemotherapy; Medicare;
cancer
ID LEUKEMIA GROUP-B; CELL LUNG-CANCER; RADIATION-THERAPY; BREAST-CANCER;
TRIALS; COMBINATION; PACLITAXEL; CISPLATIN; ETOPOSIDE; OLDER
AB Purpose:
We sought to determine the accuracy with which Medicare billing data documents elderly Medicare cancer patients' receipt of common multiagent chemotherapy regimens.
Methods:
We merged gold-standard clinical trial data from 406 elderly cancer patients known to be treated on 1 of 6 Cancer and Leukemia Group B (CALGB) breast, colorectal, and lung cancer trials (trial numbers; 9344, 9730, 9235,9732, 80203, 89803) with their Medicare claims data from Centers for Medicare and Medicaid Services (CMS). Comparing CMS chemotherapy codes to gold-standard CALGB treatment data, we estimated Medicare data's sensitivity at measuring the correct drugs and schedule for each of the multiagent chemotherapy regimens.
Results:
Overall 92% (375/406) of CALGB patients had contemporaneous CMS claims indicating receipt of chemotherapy. The overall sensitivity of CMS ambulatory claims for documenting treatment with the correct drugs and on the correct schedule (ie, all drugs had to be billed on the same day) for the 5 common multiagent chemotherapy regimens was 78% (275/354) for those potentially treated in the ambulatory setting. The sensitivity was similar for all treatment regimens: carboplatin and paclitaxel 83%, 5-fluorouracil and leucovorin 80%, fluorouracil, leucovorin, and irinotecan (FOLFIRI) 76%, doxorubicin and cyclophosphamide 75%, and cisplatin and etoposide 75%.
Conclusions:
We correctly identified at least 3-quarters of elderly Medicare cancer patients treated on a clinical trial with standard first-line multiagent chemotherapy regimens in the ambulatory setting by applying coding algorithms to their CMS claims. The algorithms may be useful in identifying cohorts of elderly Medicare patients for observational studies of the comparative effectiveness of standard multiagent chemotherapy regimens.
C1 [Lamont, Elizabeth B.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Canc Ctr, Boston, MA 02115 USA.
[Lamont, Elizabeth B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Massachusetts Gen Hosp,Canc Ctr, Boston, MA 02115 USA.
[Lan, Lan] Duke Univ, Dept Biostat, Durham, NC USA.
RP Lamont, EB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180A Longwood Ave, Boston, MA 02115 USA.
EM lamont@hcp.med.harvard.edu
FU National Cancer Institute [CA132900, CA33601]
FX Supported by grants from the National Cancer Institute: CA132900
(Lamont) and CA33601 (CALGB Statistics Center).
NR 18
TC 6
Z9 6
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0025-7079
EI 1537-1948
J9 MED CARE
JI Med. Care
PD MAR
PY 2014
VL 52
IS 3
BP E15
EP E20
DI 10.1097/MLR.0b013e31824e342f
PG 6
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA AG3NW
UT WOS:000335327400001
PM 22410411
ER
PT J
AU DeSalvo, MN
Douw, L
Tanaka, N
Reinsberger, C
Stufflebeam, SM
AF DeSalvo, Matthew N.
Douw, Linda
Tanaka, Naoaki
Reinsberger, Claus
Stufflebeam, Steven M.
TI Altered Structural Connectome in Temporal Lobe Epilepsy
SO RADIOLOGY
LA English
DT Article
ID GRAPH-THEORETICAL ANALYSIS; SURFACE-BASED ANALYSIS; NETWORKS; BRAIN;
CONNECTIVITY; SYSTEM
AB Purpose: To study differences in the whole-brain structural connectomes of patients with left temporal lobe epilepsy (TLE) and healthy control subjects.
Materials and Methods: This study was approved by the institutional review board, and all individuals gave signed informed consent. Sixty-direction diffusion-tensor imaging and magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) magnetic resonance imaging volumes were analyzed in 24 patients with left TLE and in 24 healthy control subjects. MP-RAGE volumes were segmented into 1015 regions of interest (ROIs) spanning the entire brain. Deterministic white matter tractography was performed after voxelwise tensor calculation. Weighted structural connectivity matrices were generated by using the pairwise density of connecting fibers between ROIs. Graph theoretical measures of connectivity networks were compared between groups by using linear models with permutation testing.
Results: Patients with TLE had 22%-45% reduced (P <.01) distant connectivity in the medial orbitofrontal cortex, temporal cortex, posterior cingulate cortex, and precuneus, compared with that in healthy subjects. However, local connectivity, as measured by means of network efficiency, was increased by 85%-270% (P <.01) in the medial and lateral frontal cortices, insular cortex, posterior cingulate cortex, precuneus, and occipital cortex in patients with TLE as compared with healthy subjects.
Conclusion: This study suggests that TLE involves altered structural connectivity in a network that reaches beyond the temporal lobe, especially in the default mode network. (C) RSNA, 2013
C1 [DeSalvo, Matthew N.; Douw, Linda; Tanaka, Naoaki; Stufflebeam, Steven M.] Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[DeSalvo, Matthew N.; Douw, Linda; Tanaka, Naoaki; Stufflebeam, Steven M.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA.
[Reinsberger, Claus] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA.
RP Stufflebeam, SM (reprint author), Athinoula Martinos Ctr Biomed Imaging, 149 Thirteenth St,Suite 2301, Charlestown, MA 02129 USA.
EM sms@nmr.mgh.harvard.edu
FU National Institutes of Health [P41-RR14075, R01-NS037462, R0-1NS069696,
5R01-NS060918]
FX This research was supported by the National Institutes of Health (grants
P41-RR14075, R01-NS037462, R0-1NS069696, and 5R01-NS060918).
NR 25
TC 24
Z9 24
U1 2
U2 5
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD MAR
PY 2014
VL 270
IS 3
BP 842
EP 848
DI 10.1148/radiol.13131044
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AG0WQ
UT WOS:000335136800022
PM 24475828
ER
PT J
AU Growdon, WB
Byron, V
DiGloria, C
Borger, DR
Foster, R
Winslow, J
Chenna, A
Sperinde, J
Rueda, BR
AF Growdon, Whitfield B.
Byron, Virginia
DiGloria, Celeste
Borger, Darrell R.
Foster, Rosemary
Winslow, John
Chenna, Ahmed
Sperinde, Jeffrey
Rueda, Bo R.
TI HER2 Over-Expressing High Grade Endometrial Cancer Expresses High Levels
of p95HER2 Variant
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Growdon, Whitfield B.; Byron, Virginia; DiGloria, Celeste; Borger, Darrell R.; Foster, Rosemary; Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA.
[Winslow, John; Chenna, Ahmed; Sperinde, Jeffrey] Monogram Biosci, LabCorps Specialty Testing Grp, San Francisco, CA USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2014
VL 21
IS 3
SU S
BP 94A
EP 95A
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AE2OO
UT WOS:000333813001056
ER
PT J
AU Tanwar, PS
Kaneko-Tarui, T
Teixeira, JM
AF Tanwar, Pradeep S.
Kaneko-Tarui, Tomoko
Teixeira, Jose M.
TI Constitutive Wnt/B-Catenin Signaling in Mice in the Absence of Mullerian
Inhibiting Substance/AntiMulleiran Hormone Signaling Leads to the
Development of a Polycystic Ovary Phenotype
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Tanwar, Pradeep S.; Kaneko-Tarui, Tomoko] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA USA.
[Teixeira, Jose M.] Michigan State Univ, Coll Human Med, Grand Rapids, MI USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2014
VL 21
IS 3
SU S
BP 125A
EP 126A
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AE2OO
UT WOS:000333813001144
ER
PT J
AU Guseh, S
Ecker, J
Kaimal, A
AF Guseh, Stephanie
Ecker, Jeffrey
Kaimal, Anjali
TI Appropriate and Timely Betamethasone Administration: Can We Do Better?
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Guseh, Stephanie; Kaimal, Anjali] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02115 USA.
[Ecker, Jeffrey] Massachusetts Gen Hosp, Vincent Obstet & Gynecol Dept, Div Maternal Fetal Med, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2014
VL 21
IS 3
SU S
BP 159A
EP 160A
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AE2OO
UT WOS:000333813001246
ER
PT J
AU Pastore, L
Silverman, L
Manichaikhul, A
Wang, X
Finkelstein, J
AF Pastore, L.
Silverman, L.
Manichaikhul, A.
Wang, X.
Finkelstein, J.
TI FMR1 CGG Repeat Length Variation by Race-Ethnicity in Females with
Normal Fertility
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Pastore, L.; Silverman, L.; Manichaikhul, A.; Wang, X.] Univ Virginia, Charlottesville, VA 22903 USA.
[Finkelstein, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
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 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2014
VL 21
IS 3
SU S
BP 202A
EP 202A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AE2OO
UT WOS:000333813002055
ER
PT J
AU Styer, AK
Karmon, A
Guo, L
Foster, R
DiGloria, C
Rueda, BR
AF Styer, Aaron K.
Karmon, Anatte
Guo, Lankai
Foster, Rosemary
DiGloria, Celeste
Rueda, Bo R.
TI Defining Ethnic Specific MicroRNA Expression Signatures and Clinical
Characteristics of Uterine Fibroids
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Styer, Aaron K.; Karmon, Anatte; Guo, Lankai; Foster, Rosemary; DiGloria, Celeste; Rueda, Bo R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Dept Obstet & Gynecol,Vincent Ctr Reprod, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2014
VL 21
IS 3
SU S
BP 317A
EP 317A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AE2OO
UT WOS:000333813003063
ER
PT J
AU Phillippe, M
Oppenheimer, K
Sweet, LM
AF Phillippe, Mark
Oppenheimer, Karen
Sweet, Leigh M.
TI The Synergistic Innate Immune Response to Bacterial and Viral PAMPs by
the Pregnant Mouse Uterus
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Phillippe, Mark] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Dept Obstet & Gynecol, Boston, MA 02114 USA.
[Oppenheimer, Karen; Sweet, Leigh M.] Univ Vermont, Burlington, VT USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2014
VL 21
IS 3
SU S
BP 336A
EP 337A
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AE2OO
UT WOS:000333813003121
ER
PT J
AU Veal, CT
Berk, T
Phillippe, M
AF Veal, Christopher T.
Berk, Tucker
Phillippe, Mark
TI Expression of Functional TLRs in Human Uterine Myocytes
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Veal, Christopher T.; Berk, Tucker; Phillippe, Mark] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA.
[Veal, Christopher T.] Univ Vermont, Coll Med, Burlington, VT USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2014
VL 21
IS 3
SU S
BP 381A
EP 381A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AE2OO
UT WOS:000333813003249
ER
PT J
AU Rana, S
Rajakumar, A
Geahchan, C
Cerdeira, ASA
Salahuddin, S
Burke, S
George, E
Granger, JP
Karumanchi, SA
AF Rana, Sarosh
Rajakumar, Augustine
Geahchan, Carl
Cerdeira, Ana Sofi A.
Salahuddin, Saira
Burke, Suzanne
George, Eric
Granger, Joey P.
Karumanchi, S. Ananth
TI Ouabain Downregulates sFlt1 Production by Inhibiting HSP27 Dependent
HIF1 Expression
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Rana, Sarosh; Rajakumar, Augustine; Geahchan, Carl; Cerdeira, Ana Sofi A.; Salahuddin, Saira; Burke, Suzanne; Karumanchi, S. Ananth] BIDMC, Boston, MA USA.
[George, Eric; Granger, Joey P.] Univ Mississippi, Med Ctr, Jackson, MS USA.
NR 0
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 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2014
VL 21
IS 3
SU S
BP 396A
EP 396A
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AE2OO
UT WOS:000333813003294
ER
PT J
AU Wang, N
Satirapod, C
Ohguchi, Y
Tilly, JL
AF Wang, Ning
Satirapod, Chonthicha
Ohguchi, Yasuyo
Tilly, Jonathan L.
TI Oocytes Generated during Adulthood Contribute to Natural Fertility in
Mice
SO REPRODUCTIVE SCIENCES
LA English
DT Meeting Abstract
C1 [Wang, Ning; Satirapod, Chonthicha; Ohguchi, Yasuyo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept OB GYN, Boston, MA USA.
[Tilly, Jonathan L.] Northeastern Univ, Dept Biol, Boston, MA 02115 USA.
NR 0
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 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAR
PY 2014
VL 21
IS 3
SU S
BP 416A
EP 417A
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AE2OO
UT WOS:000333813003353
ER
PT J
AU Safren, SA
Gonzalez, JS
Wexler, DJ
Psaros, C
Delahanty, LM
Blashill, AJ
Margolina, AI
Cagliero, E
AF Safren, Steven A.
Gonzalez, Jeffrey S.
Wexler, Deborah J.
Psaros, Christina
Delahanty, Linda M.
Blashill, Aaron J.
Margolina, Aleksandra I.
Cagliero, Enrico
TI A Randomized Controlled Trial of Cognitive Behavioral Therapy for
Adherence and Depression (CBT-AD) in Patients With Uncontrolled Type 2
Diabetes
SO DIABETES CARE
LA English
DT Article
ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; MEDICATION ADHERENCE;
COLLABORATIVE CARE; GLYCEMIC CONTROL; SELF-CARE; DSM-IV; MELLITUS;
METAANALYSIS; MANAGEMENT; MORTALITY
AB OBJECTIVETo test cognitive behavioral therapy for adherence and depression (CBT-AD) in type 2 diabetes. We hypothesized that CBT-AD would improve adherence; depression; and, secondarily, hemoglobin A(1c) (A1C).RESEARCH DESIGN AND METHODSEighty-seven adults with unipolar depression and uncontrolled type 2 diabetes received enhanced treatment as usual (ETAU), including medication adherence, self-monitoring of blood glucose (SMBG), and lifestyle counseling; a provider letter documented psychiatric diagnoses. Those randomized to the intervention arm also received 9-11 sessions of CBT-AD.RESULTSImmediately after acute treatment (4 months), adjusting for baseline, CBT-AD had 20.7 percentage points greater oral medication adherence on electronic pill cap (95% CI -31.14 to -10.22, P = 0.000); 30.2 percentage points greater SMBG adherence through glucometer downloads (95% CI -42.95 to -17.37, P = 0.000); 6.44 points lower depression scores on the Montgomery-Asberg Depression Rating Scale (95% CI 2.33-10.56, P = 0.002); 0.74 points lower on the Clinical Global Impression (95% CI 0.16-1.32, P = 0.01); and 0.72 units lower A1C (95% CI 0.29-1.15, P = 0.001) relative to ETAU. Analyses of 4-, 8-, and 12-month follow-up time points indicated that CBT-AD maintained 24.3 percentage points higher medication adherence (95% CI -38.2 to -10.3, P = 0.001); 16.9 percentage points greater SMBG adherence (95% CI -33.3 to -0.5, P = 0.043); and 0.63 units lower A1C (95% CI 0.06-1.2, P = 0.03) after acute treatment ended. For depression, there was some evidence of continued improvement posttreatment, but no between-group differences.CONCLUSIONSCBT-AD is an effective intervention for adherence, depression, and glycemic control, with enduring and clinically meaningful benefits for diabetes self-management and glycemic control in adults with type 2 diabetes and depression.
C1 [Safren, Steven A.; Psaros, Christina; Blashill, Aaron J.; Margolina, Aleksandra I.] Massachusetts Gen Hosp, Dept Psychiat, Behav Med Serv, Boston, MA 02114 USA.
[Safren, Steven A.; Wexler, Deborah J.; Psaros, Christina; Delahanty, Linda M.; Blashill, Aaron J.; Margolina, Aleksandra I.; Cagliero, Enrico] Harvard Univ, Sch Med, Boston, MA USA.
[Gonzalez, Jeffrey S.] Yeshiva Univ, Ferkauf Grad Sch Psychol, Bronx, NY USA.
[Gonzalez, Jeffrey S.] Yeshiva Univ, Albert Einstein Coll Med, Diabet Res Ctr, Bronx, NY USA.
[Wexler, Deborah J.; Delahanty, Linda M.; Cagliero, Enrico] Massachusetts Gen Hosp, Dept Med, MGH Diabet Ctr, Boston, MA 02114 USA.
RP Safren, SA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Behav Med Serv, Boston, MA 02114 USA.
EM ssafren@partners.org
FU National Institute of Mental Health [R01-MH-078571]; Harvard Catalyst,
Harvard Clinical and Translational Science Center; National Institutes
of Health [1UL1-RR-025758-03]; National Institute of Diabetes and
Digestive and Kidney Diseases Career Development Award [K23-DK-080228];
[DK-020541]; [1K23-MH-096647]
FX This project was supported by National Institute of Mental Health grant
R01-MH-078571 (principal investigator: S. A. S.). Additional support
came from the Harvard Catalyst, Harvard Clinical and Translational
Science Center, by National Institutes of Health grant 1UL1-RR-025758-03
for a portion of the nurse and dietitian study visits. J.S.G. is
partially supported by grant DK-020541. D.J.W. was supported by a
National Institute of Diabetes and Digestive and Kidney Diseases Career
Development Award (K23-DK-080228). A.J.B. is supported by grant
1K23-MH-096647.
NR 39
TC 43
Z9 44
U1 6
U2 33
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD MAR
PY 2014
VL 37
IS 3
BP 625
EP 633
DI 10.2337/dc13-0816
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AB3RT
UT WOS:000331708600015
PM 24170758
ER
PT J
AU Kim, C
Cleary, PA
Cowie, CC
Braffett, BH
Dunn, RL
Larkin, ME
Gatcomb, PM
Wessells, HB
Nathan, DM
Sarma, AV
AF Kim, Catherine
Cleary, Patricia A.
Cowie, Catherine C.
Braffett, Barbara H.
Dunn, Rodney L.
Larkin, Mary E.
Gatcomb, Patricia M.
Wessells, Hunter B.
Nathan, David M.
Sarma, Aruna V.
CA DCCT EDIC Res Grp
TI Effect of Glycemic Treatment and Microvascular Complications on
Menopause in Women With Type 1 Diabetes in the Diabetes Control and
Complications Trial/Epidemiology of Diabetes Interventions and
Complications (DCCT/EDIC) Cohort
SO DIABETES CARE
LA English
DT Article
ID PREMATURE OVARIAN FAILURE; ANTI-MULLERIAN HORMONE; INHIBIN B LEVELS;
MELLITUS; TRIAL; EPIDEMIOLOGY; AUTOIMMUNITY; DYSFUNCTION; THERAPY;
HISTORY
AB OBJECTIVEWe examined the impact of intensive versus conventional diabetes treatment upon menopause among women with type 1 diabetes in the Diabetes Control and Complications Trial (DCCT), a randomized controlled trial of intensive diabetes treatment, and its observational follow-up, the Epidemiology of Diabetes Interventions and Complications (EDIC) study.RESEARCH DESIGN AND METHODSIn a secondary analysis of women in the DCCT/EDIC (n = 657), outcomes were the cumulative incidences of natural menopause and surgical menopause. Cox regression analyses were used to examine associations with treatment group, time-varying estimates of hemoglobin A(1c) (HbA(1c)), insulin dosage, BMI, and microvascular complications (retinopathy, nephropathy, and neuropathy).RESULTSBy EDIC year 18, after an average of 28 years of follow-up, 240 (38%) women had experienced natural menopause and 115 (18%) women had experienced surgical menopause. Age at natural menopause was similar in the intensive versus conventional groups (49.9 vs. 49.0 years; P = 0.28), and age at surgical menopause was similar in the intensive versus conventional groups (40.8 vs. 42.0 years; P = 0.31). In multivariable models, treatment group, HbA(1c), and microvascular complications were not associated with risk of natural or surgical menopause. Each 10 unit/day increase in insulin dosage decreased risk of natural menopause (hazard ratio [HR] 0.91, 95% CI 0.75-0.98) and each kg/m(2) increase in BMI increased risk of surgical menopause (HR 1.08, 95% CI 1.00-1.16).CONCLUSIONSIn the DCCT/EDIC, intensive versus conventional treatment group and HbA(1c) level were not associated with menopause risk. Greater insulin dose was associated with lower menopause risk.
C1 [Kim, Catherine] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA.
[Kim, Catherine] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.
[Cleary, Patricia A.; Braffett, Barbara H.] George Washington Univ, Biostat Ctr, Rockville, MD USA.
[Cowie, Catherine C.] Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD USA.
[Dunn, Rodney L.; Sarma, Aruna V.] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA.
[Larkin, Mary E.; Nathan, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Diabet, Boston, MA USA.
[Gatcomb, Patricia M.] Yale Univ, Dept Med, New Haven, CT 06520 USA.
[Wessells, Hunter B.] Univ Washington, Dept Urol, Seattle, WA 98195 USA.
RP Kim, C (reprint author), Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA.
EM cathkim@umich.edu
FU Division of Diabetes Endocrinology and Metabolic Diseases of the
National Institute of Diabetes and Digestive and Kidney Diseases
[U01-DK-094176, U01-DK-094157]; National Eye Institute; National
Institute of Neurological Disorders and Stroke; Genetic Clinical
Research Centers Program; Clinical and Translational Science Center
Program, Bethesda, MD; U01 Cooperative Agreement; [R01-DK-083297]
FX The DCCT/EDIC has been supported by U01 Cooperative Agreement grants
(1982-93, 2011-2016) and contracts (1982-2011) with the Division of
Diabetes Endocrinology and Metabolic Diseases of the National Institute
of Diabetes and Digestive and Kidney Diseases (current grant numbers
U01-DK-094176 and U01-DK-094157) and through support by the National Eye
Institute, the National Institute of Neurological Disorders and Stroke,
the Genetic Clinical Research Centers Program (1993-2007), and the
Clinical and Translational Science Center Program (2006-present),
Bethesda, MD. Additional support for C. K. was provided by
R01-DK-083297.
NR 20
TC 8
Z9 8
U1 0
U2 1
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD MAR
PY 2014
VL 37
IS 3
BP 701
EP 708
DI 10.2337/dc13-1746
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AB3RT
UT WOS:000331708600025
PM 24170751
ER
PT J
AU Novak, V
Milberg, W
Hao, Y
Munshi, M
Novak, P
Galica, A
Manor, B
Roberson, P
Craft, S
Abduljalil, A
AF Novak, Vera
Milberg, William
Hao, Ying
Munshi, Medha
Novak, Peter
Galica, Andrew
Manor, Bradley
Roberson, Paula
Craft, Suzanne
Abduljalil, Amir
TI Enhancement of Vasoreactivity and Cognition by Intranasal Insulin in
Type 2 Diabetes
SO DIABETES CARE
LA English
DT Article
ID CEREBRAL-BLOOD-FLOW; IMPAIRED OLDER-ADULTS; BRAIN; MEMORY;
HYPERINTENSITIES; PRESSURE; MELLITUS; DELIVERY; DISEASE; ATROPHY
AB OBJECTIVETo determine acute effects of intranasal insulin on regional cerebral perfusion and cognition in older adults with type 2 diabetes mellitus (DM).RESEARCH DESIGN AND METHODSThis was a proof-of-concept, randomized, double-blind, placebo-controlled intervention evaluating the effects of a single 40-IU dose of insulin or saline on vasoreactivity and cognition in 15 DM and 14 control subjects. Measurements included regional perfusion, vasodilatation to hypercapnia with 3-Tesla MRI, and neuropsychological evaluation.RESULTSIntranasal insulin administration was well tolerated and did not affect systemic glucose levels. No serious adverse events were reported. Across all subjects, intranasal insulin improved visuospatial memory (P 0.05). In the DM group, an increase of perfusion after insulin administration was greater in the insular cortex compared with the control group (P = 0.0003). Cognitive performance after insulin administration was related to regional vasoreactivity. Improvements of visuospatial memory after insulin administration in the DM group (R-adjusted(2) = 0.44, P = 0.0098) and in the verbal fluency test in the control group (R-adjusted(2) = 0.64, P = 0.0087) were correlated with vasodilatation in the middle cerebral artery territory.CONCLUSIONSIntranasal insulin administration appears safe, does not affect systemic glucose control, and may provide acute improvements of cognitive function in patients with type 2 DM, potentially through vasoreactivity mechanisms. Intranasal insulin-induced changes in cognitive function may be related to vasodilatation in the anterior brain regions, such as insular cortex that regulates attention-related task performance. Larger studies are warranted to identify long-term effects and predictors of positive cognitive response to intranasal insulin therapy.
C1 [Novak, Vera; Hao, Ying; Munshi, Medha; Galica, Andrew; Manor, Bradley] Harvard Univ, Sch Med, Dept Neurol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
[Milberg, William] VA Boston Healthcare, Boston Div, New England Geriatr Res Educ & Clin Ctr, Boston, MA USA.
[Milberg, William] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Hao, Ying] Peking Univ, Acad Adv Interdisciplinary Studies, Beijing 100871, Peoples R China.
[Munshi, Medha] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Novak, Peter] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA.
[Roberson, Paula] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA.
[Craft, Suzanne] Wake Forest Univ, Bowman Gray Sch Med, Div Gerontol & Geriatr Med, Winston Salem, NC USA.
[Abduljalil, Amir] Ohio State Univ, Dept Radiol, Columbus, OH 43210 USA.
RP Novak, V (reprint author), Harvard Univ, Sch Med, Dept Neurol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
EM vnovak@bidmc.harvard.edu
FU National Institutes of Health (NIH)-National Institute of Diabetes and
Digestive and Kidney Diseases [5R21-DK-084463-02]; NIH-National
Institute on Aging (NIA) [1R01-AG-0287601-A2]; China Scholarship Council
[201206010220]; NIH-NIA [R01-AG-027415]; Harvard Clinical and
Translational Science Center (National Center for Research Resources and
the National Center for Advancing Translational Sciences, NIH)
[1KL2RR025757-04, 8KL2TR000168-05, 8UL1TR000170-05]; Translational
Research Center for Traumatic Brain Injury (TBI) and Stress Disorders
(TRACTS); VA Rehabilitation Research and Development Traumatic Brain
Injury Center of Excellence [B6796-C]; VA Merit Review Award; Harvard
Catalyst; Harvard University
FX V.N. has received grants from the National Institutes of Health
(NIH)-National Institute of Diabetes and Digestive and Kidney Diseases
(5R21-DK-084463-02) and the NIH-National Institute on Aging (NIA)
(1R01-AG-0287601-A2) related to this study, and V.N., M.M., P.N., A.G.,
B.M., P.R., and S.C. received salaries from these grants. Y.H. received
grant support from the China Scholarship Council (201206010220). S.C.
has received a grant from the NIH-NIA (R01-AG-027415). B.M. received a
KL2 Medical Research Investigator Training (MeRIT) award
(1KL2RR025757-04) from the Harvard Clinical and Translational Science
Center (National Center for Research Resources and the National Center
for Advancing Translational Sciences, NIH award 8KL2TR000168-05). W.M.
was also supported by the Translational Research Center for Traumatic
Brain Injury (TBI) and Stress Disorders (TRACTS), a VA Rehabilitation
Research and Development Traumatic Brain Injury Center of Excellence
(B6796-C), and VA Merit Review Award to Regina McGlinchey. This work was
conducted with support from Harvard Catalyst, the Harvard Clinical and
Translational Science Center (National Center for Research Resources and
the National Center for Advancing Translational Sciences, NIH award
8UL1TR000170-05 and financial contributions from Harvard University and
its affiliated academic health care centers).
NR 36
TC 29
Z9 35
U1 0
U2 7
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD MAR
PY 2014
VL 37
IS 3
BP 751
EP 759
DI 10.2337/dc13-1672
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AB3RT
UT WOS:000331708600031
PM 24101698
ER
PT J
AU Nadeau, KJ
Mather, KJ
Arslanian, SA
Buchanan, TA
Caprio, S
Edelstein, SL
Ehrmann, DA
Savage, PJ
Kahn, SE
Mokhlesi, B
Van Cauter, E
Montgomery, BK
Palmer, J
Utzschneider, K
Mather, KJ
Chisholm, R
Hannon, T
Nadeau, KJ
Zeitler, P
Arslanian, SA
Caprio, S
Buchanan, TA
Xiang, A
Edelstein, SL
Lachin, JM
Savage, PJ
AF Nadeau, Kristen J.
Mather, Kieren J.
Arslanian, Silva A.
Buchanan, Thomas A.
Caprio, Sonia
Edelstein, Sharon L.
Ehrmann, David A.
Savage, Peter J.
Kahn, Steven E.
Mokhlesi, Babak
Van Cauter, Eve
Montgomery, Brenda K.
Palmer, Jerry
Utzschneider, Kristina
Mather, Kieren J.
Chisholm, Robin
Hannon, Tamara
Nadeau, Kristen J.
Zeitler, Phil
Arslanian, Silva A.
Caprio, Sonia
Buchanan, Thomas A.
Xiang, Anny
Edelstein, Sharon L.
Lachin, John M.
Savage, Peter J.
CA RISE Consortium
TI Restoring Insulin Secretion (RISE): Design of Studies of beta-Cell
Preservation in Prediabetes and Early Type 2 Diabetes Across the Life
Span
SO DIABETES CARE
LA English
DT Article
ID IMPAIRED GLUCOSE-TOLERANCE; STYLE INTERVENTION; GLYCEMIC CONTROL;
POSTPRANDIAL HYPERGLYCEMIA; PREVENTION PROGRAM; BARIATRIC SURGERY;
CONTROLLED-TRIAL; HISPANIC WOMEN; FOLLOW-UP; METFORMIN
AB OBJECTIVEThe Restoring Insulin Secretion (RISE) Consortium is testing interventions designed to preserve or improve -cell function in prediabetes or early type 2 diabetes.RESEARCH DESIGN AND METHODS-Cell function is measured using hyperglycemic clamps and oral glucose tolerance tests (OGTTs). The adult medication protocol randomizes participants to 12 months of placebo, metformin alone, liraglutide plus metformin, or insulin (3 months) followed by metformin (9 months). The pediatric medication protocol randomizes participants to metformin or insulin followed by metformin. The adult surgical protocol randomizes participants to gastric banding or metformin (24 months). Adult medication protocol inclusion criteria include fasting plasma glucose 95-125 mg/dL (5.3-6.9 mmol/L), OGTT 2-h glucose 140 mg/dL (7.8 mmol/L), HbA(1c) 5.8-7.0% (40-53 mmol/mol), and BMI 25-40 kg/m(2). Adult surgical protocol criteria are similar, except for fasting plasma glucose 90 mg/dL (5.0 mmol/L), BMI 30-40 kg/m(2), HbA(1c) <7.0% (<53 mmol/mol), and diabetes duration <12 months. Pediatric inclusion criteria include fasting plasma glucose 90 mg/dL (5.0 mmol/L), 2-h glucose 140 mg/dL (7.8 mmol/L), HbA(1c) 8.0% (64 mmol/mol), BMI >85th percentile and 50 kg/m(2), 10-19 years of age, and diabetes <6 months.RESULTSPrimary outcomes are clamp-derived glucose-stimulated C-peptide secretion and maximal C-peptide response to arginine during hyperglycemia. Measurements are made at baseline, after 12 months on treatment, and 3 months after treatment withdrawal (medication protocols) or 24 months postintervention (surgery protocol). OGTT-derived measures are also obtained at these time points.CONCLUSIONSRISE is determining whether medication or surgical intervention strategies can mitigate progressive -cell dysfunction in adults and youth with prediabetes or early type 2 diabetes.
C1 [Nadeau, Kristen J.; Mather, Kieren J.; Chisholm, Robin; Hannon, Tamara] Univ Colorado Denver, Denver, CO 80202 USA.
[Nadeau, Kristen J.; Mather, Kieren J.; Chisholm, Robin; Hannon, Tamara] Childrens Hosp Colorado, Colorado Springs, CO USA.
[Mather, Kieren J.; Montgomery, Brenda K.; Palmer, Jerry; Utzschneider, Kristina] Indiana Univ, Sch Med, Bloomington, IN 47405 USA.
[Arslanian, Silva A.; Nadeau, Kristen J.; Zeitler, Phil] Univ Pittsburgh, Med Ctr, Childrens Hosp Pittsburgh, Pittsburgh, PA 15260 USA.
[Buchanan, Thomas A.; Caprio, Sonia] Univ So Calif, Keck Sch Med, Los Angeles, CA 90089 USA.
[Caprio, Sonia; Arslanian, Silva A.] Yale Univ, Dept Pediat, New Haven, CT 06520 USA.
[Edelstein, Sharon L.; Buchanan, Thomas A.; Xiang, Anny; Edelstein, Sharon L.; Lachin, John M.; Savage, Peter J.] George Washington Univ, Ctr Biostat, Washington, DC 20052 USA.
[Ehrmann, David A.] Univ Chicago, Clin Res Ctr, Chicago, IL 60637 USA.
[Savage, Peter J.; Kahn, Steven E.; Mokhlesi, Babak; Van Cauter, Eve] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA.
[Savage, Peter J.; Kahn, Steven E.; Mokhlesi, Babak; Van Cauter, Eve] Univ Washington, Seattle, WA 98195 USA.
[Caprio, Sonia] Kaiser Permanente So Calif, Los Angeles, CA USA.
RP Edelstein, SL (reprint author), Univ Colorado Denver, Denver, CO 80202 USA.
EM rise@bsc.gwu.edu
FU NIDDK [Chicago DK-094431, Denver DK-094467, Indiana DK-094438, Los
Angeles DK-094430, Seattle DK-09440]; Department of Veterans Affairs
FX RISE is supported by grants from the NIDDK (Chicago DK-094431, Denver
DK-094467, Indiana DK-094438, Los Angeles DK-094430, and Seattle
DK-09440) and the Department of Veterans Affairs.
NR 41
TC 8
Z9 8
U1 0
U2 3
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD MAR
PY 2014
VL 37
IS 3
BP 780
EP 788
DI 10.2337/dc13-1879
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AB3RT
UT WOS:000331708600035
ER
PT J
AU Alkire, BC
Juliano, AF
Hartnick, CJ
AF Alkire, Blake C.
Juliano, Amy F.
Hartnick, Christopher J.
TI Neck Mass in an Adolescent Male
SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY
LA English
DT Editorial Material
ID PYRIFORM SINUS FISTULA; BRANCHIAL ANOMALIES; IMAGING FINDINGS;
MANAGEMENT; INFECTION
C1 [Alkire, Blake C.; Juliano, Amy F.; Hartnick, Christopher J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA.
RP Hartnick, CJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA.
EM christopher_hartnick@meei.harvard.edu
NR 10
TC 0
Z9 0
U1 0
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6181
EI 2168-619X
J9 JAMA OTOLARYNGOL
JI JAMA Otolaryngol-Head Neck Surg.
PD MAR
PY 2014
VL 140
IS 3
BP 275
EP 276
DI 10.1001/jamaoto.2013.6230
PG 2
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA AF4HQ
UT WOS:000334673000019
PM 24408774
ER
PT J
AU Balentine, CJ
Naik, AD
Robinson, CN
Petersen, NJ
Chen, GJ
Berger, DH
Anaya, DA
AF Balentine, Courtney J.
Naik, Aanand D.
Robinson, Celia N.
Petersen, Nancy J.
Chen, G. John
Berger, David H.
Anaya, Daniel A.
TI Association of High-Volume Hospitals With Greater Likelihood of
Discharge to Home Following Colorectal Surgery
SO JAMA SURGERY
LA English
DT Article
ID QUALITY-OF-CARE; INPATIENT SURGERY; UNITED-STATES; MORTALITY;
COMPLICATIONS; OUTCOMES; CANCER; IMPACT; COLECTOMY; SURVIVAL
AB IMPORTANCE Discharge disposition is a patient-centered quality metric that reflects differences in quality of life and recovery following surgery. The effect of hospital volume on quality of recovery measured by rates of successful discharge to home remains unclear.
OBJECTIVE To test the hypothesis that patients having colorectal surgery at high-volume hospitals would more likely be discharged to home rather than discharged to skilled rehabilitation facilities to complete recovery.
DESIGN, SETTING, AND PARTICIPANTS Longitudinal analysis of 2008 hospital inpatient data to identify patients undergoing colorectal surgery who survived to discharge. The setting was the Nationwide Inpatient Sample, the largest all-payer inpatient care database, containing data from more than 1000 hospitals. Participants were 280 644 patients (>= 18 years) who underwent colorectal resections for benign or malignant disease and survived to discharge.
MAIN OUTCOMES AND MEASURES The primary end point was discharge to home (with or without home health care) vs discharge to skilled facilities (skilled nursing, short-term recovery, or rehabilitation hospitals or other institutions). The secondary end point was discharge to home with home health care rather than to a skilled facility for patients with postdischarge care needs. Multiple logistic regression using robust standard errors was used to compute the odds ratios of each outcome based on hospital volume, while adjusting for other important variables.
RESULTS The odds of discharge to home vs discharge to skilled facilities were significantly greater in high-volume hospitals compared with low-volume hospitals (odds ratio, 2.09; 95% CI, 1.70-2.56), with an absolute increase of 9%. For patients with postdischarge care needs, high-volume hospitals were less likely than low-volume hospitals to use skilled facilities rather than home health care (odds ratio, 0.35; 95% CI, 0.27-0.45), with an absolute difference of 10%.
CONCLUSIONS AND RELEVANCE Patients having colorectal surgery at high-volume hospitals are significantly more likely to recover and return home after surgery than individuals having operations at low-volume hospitals. This study is the first step in a process of identifying which features of high-volume hospitals contribute toward desirable outcomes. Efforts to identify the reasons for improved recovery at high-volume hospitals can help lower-volume hospitals adopt beneficial practices.
C1 [Balentine, Courtney J.; Naik, Aanand D.; Petersen, Nancy J.; Chen, G. John; Berger, David H.; Anaya, Daniel A.] Michael E DeBakey VA Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Houston, TX 77030 USA.
[Balentine, Courtney J.; Robinson, Celia N.; Berger, David H.; Anaya, Daniel A.] DeBakey Vet Affairs Med Ctr, Houston, TX USA.
[Balentine, Courtney J.; Berger, David H.; Anaya, Daniel A.] Baylor Coll Med, Michael E DeBakey Dept Surg, Houston, TX 77030 USA.
[Naik, Aanand D.; Chen, G. John] Baylor Coll Med, Dept Med, Div Geriatr, Houston, TX 77030 USA.
[Naik, Aanand D.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
RP Anaya, DA (reprint author), Michael E DeBakey VA Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Room 152,2002 Holcombe Blvd, Houston, TX 77030 USA.
EM danaya@bcm.edu
FU National Institute on Aging [K23AG027144]; Doris Duke Charitable
Foundation Clinical Scientist Development Award; Baylor College of
Medicine Comprehensive Cancer Training Program Grant Cancer Prevention &
Research Institute of Texas [101499]
FX Dr Naik is supported by grant K23AG027144 from the National Institute on
Aging and by a Doris Duke Charitable Foundation Clinical Scientist
Development Award. Dr Robinson has received support from Baylor College
of Medicine Comprehensive Cancer Training Program Grant Cancer
Prevention & Research Institute of Texas, Research Project 101499. No
other disclosures were reported.
NR 26
TC 15
Z9 15
U1 1
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6254
EI 2168-6262
J9 JAMA SURG
JI JAMA Surg.
PD MAR
PY 2014
VL 149
IS 3
BP 244
EP 251
DI 10.1001/jamasurg.2013.3838
PG 8
WC Surgery
SC Surgery
GA AF3JX
UT WOS:000334609400007
PM 24430092
ER
PT J
AU Brinton, LA
Cook, MB
McCormack, V
Johnson, KC
Olsson, H
Casagrande, JT
Cooke, R
Falk, RT
Gapstur, SM
Gaudet, MM
Gaziano, JM
Gkiokas, G
Guenel, P
Henderson, BE
Hollenbeck, A
Hsing, AW
Kolonel, LN
Isaacs, C
Lubin, JH
Michels, KB
Negri, E
Parisi, D
Petridou, ET
Pike, MC
Riboli, E
Sesso, HD
Snyder, K
Swerdlow, AJ
Trichopoulos, D
Ursin, G
van den Brandt, PA
Van Den Eeden, SK
Weiderpass, E
Willett, WC
Ewertz, M
Thomas, DB
AF Brinton, Louise A.
Cook, Michael B.
McCormack, Valerie
Johnson, Kenneth C.
Olsson, Hakan
Casagrande, John T.
Cooke, Rosie
Falk, Roni T.
Gapstur, Susan M.
Gaudet, Mia M.
Gaziano, J. Michael
Gkiokas, Georgios
Guenel, Pascal
Henderson, Brian E.
Hollenbeck, Albert
Hsing, Ann W.
Kolonel, Laurence N.
Isaacs, Claudine
Lubin, Jay H.
Michels, Karin B.
Negri, Eva
Parisi, Dominick
Petridou, Eleni Th.
Pike, Malcolm C.
Riboli, Elio
Sesso, Howard D.
Snyder, Kirk
Swerdlow, Anthony J.
Trichopoulos, Dimitrios
Ursin, Giske
van den Brandt, Piet A.
Van Den Eeden, Stephen K.
Weiderpass, Elisabete
Willett, Walter C.
Ewertz, Marianne
Thomas, David B.
CA European Rare Canc Study Grp
TI Anthropometric and Hormonal Risk Factors for Male Breast Cancer: Male
Breast Cancer Pooling Project Results
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID BASE-LINE CHARACTERISTICS; KLINEFELTER-SYNDROME; PROSTATE-CANCER; MEN;
COHORT; EPIDEMIOLOGY; NUTRITION; HEALTH; TESTOSTERONE; MORTALITY
AB The etiology of male breast cancer is poorly understood, partly because of its relative rarity. Although genetic factors are involved, less is known regarding the role of anthropometric and hormonally related risk factors.
In the Male Breast Cancer Pooling Project, a consortium of 11 casecontrol and 10 cohort investigations involving 2405 case patients (n 1190 from casecontrol and n 1215 from cohort studies) and 52013 control subjects, individual participant data were harmonized and pooled. Unconditional logistic regression generated study designspecific (casecontrol/cohort) odds ratios (ORs) and 95% confidence intervals (CIs), with exposure estimates combined using fixed effects meta-analysis. All statistical tests were two-sided.
Risk was statistically significantly associated with weight (highest/lowest tertile: OR 1.36; 95% CI 1.18 to 1.57), height (OR 1.18; 95% CI 1.01 to 1.38), and body mass index (BMI; OR 1.30; 95% CI 1.12 to 1.51), with evidence that recent rather than distant BMI was the strongest predictor. Klinefelter syndrome (OR 24.7; 95% CI 8.94 to 68.4) and gynecomastia (OR 9.78; 95% CI 7.52 to 12.7) were also statistically significantly associated with risk, relations that were independent of BMI. Diabetes also emerged as an independent risk factor (OR 1.19; 95% CI 1.04 to 1.37). There were also suggestive relations with cryptorchidism (OR 2.18; 95% CI 0.96 to 4.94) and orchitis (OR 1.43; 95% CI 1.02 to 1.99). Although age at onset of puberty and histories of infertility were unrelated to risk, never having had children was statistically significantly related (OR 1.29; 95% CI 1.01 to 1.66). Among individuals diagnosed at older ages, a history of fractures was statistically significantly related (OR 1.41; 95% CI 1.07 to 1.86).
Consistent findings across casecontrol and cohort investigations, complemented by pooled analyses, indicated important roles for anthropometric and hormonal risk factors in the etiology of male breast cancer. Further investigation should focus on potential roles of endogenous hormones.
C1 [Brinton, Louise A.; Cook, Michael B.; Falk, Roni T.; Lubin, Jay H.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[McCormack, Valerie] Int Agcy Res Canc, Sect Environm & Radiat, F-69372 Lyon, France.
[Johnson, Kenneth C.] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON, Canada.
[Olsson, Hakan] Lund Univ, Dept Oncol, Lund, Sweden.
[Casagrande, John T.; Henderson, Brian E.; Pike, Malcolm C.; Ursin, Giske] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA.
[Cooke, Rosie; Swerdlow, Anthony J.] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England.
[Gapstur, Susan M.; Gaudet, Mia M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Michels, Karin B.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA.
[Sesso, Howard D.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Sesso, Howard D.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA.
[Gaziano, J. Michael] VA Boston Healthcare Syst, MAVERIC, Boston, MA USA.
[Gkiokas, Georgios] Aretaie Univ Hosp, Dept Surg, Athens, Greece.
[Guenel, Pascal] Univ Paris Sud, INSERM, Ctr Res Epidemiol & Populat Hlth, U1018, Villejuif, France.
[Hollenbeck, Albert] AARP, AARP Res, Washington, DC USA.
[Hsing, Ann W.] Canc Prevent Inst Calif, Fremont, CA USA.
[Hsing, Ann W.] Stanford Univ, Div Epidemiol, Dept Hlth Res & Policy, Palo Alto, CA 94304 USA.
[Hsing, Ann W.] Stanford Univ, Stanford Canc Inst, Stanford Sch Med, Stanford, CA USA.
[Kolonel, Laurence N.] Univ Hawaii, Ctr Canc, Canc Epidemiol Program, Honolulu, HI 96822 USA.
[Isaacs, Claudine] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
[Michels, Karin B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Michels, Karin B.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Negri, Eva; Trichopoulos, Dimitrios] Ist Richerche Farmacol, Milan, Italy.
[Parisi, Dominick; Snyder, Kirk] IMS Inc, Rockville, MD USA.
[Petridou, Eleni Th.] Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, GR-11527 Athens, Greece.
[Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England.
[Sesso, Howard D.] Inst Canc Res, Div Prevent Med, London SW3 6JB, England.
[Sesso, Howard D.] Inst Canc Res, Div Aging, London SW3 6JB, England.
[Swerdlow, Anthony J.] Inst Canc Res, Div Breast Canc Res, London SW3 6JB, England.
[Ursin, Giske; Weiderpass, Elisabete] Canc Registry Norway, Oslo, Norway.
[Ursin, Giske] Univ Oslo, Inst Basic Med Sci, Dept Nutr, Oslo, Norway.
[van den Brandt, Piet A.] Maastricht Univ, Dept Epidemiol, Maastricht, Netherlands.
[Van Den Eeden, Stephen K.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Weiderpass, Elisabete] Arct Univ Norway, Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway.
[Weiderpass, Elisabete] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Weiderpass, Elisabete] Samfundet Folkhalsan, Helsinki, Finland.
[Ewertz, Marianne] Univ Southern Denmark, Inst Clin Res, Odense Univ Hosp, Dept Oncol, Odense, Denmark.
[Thomas, David B.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA.
RP Brinton, LA (reprint author), NCI, NIH, Hormonal & Reprod Epidemiol Branch, 9609 Med Ctr Dr,Rm 7-E102,MSC 9774, Bethesda, MD 20892 USA.
EM brinton@nih.gov
RI Brinton, Louise/G-7486-2015; Cook, Michael/A-5641-2009; Weiderpass,
Elisabete/M-4029-2016
OI Brinton, Louise/0000-0003-3853-8562; Cook, Michael/0000-0002-0533-7302;
Weiderpass, Elisabete/0000-0003-2237-0128
FU European Research Council [ERC-2011-294576]; National Institutes of
Health, Bethesda, Maryland; Institute of Cancer Research acknowledges
National Health Service; Deutsche Krebshilfe; Deutsches
Krebsforschungszentrum; Federal Ministry of Education and Research
Germany; Swedish Cancer Society; Swedish Scientific Council; Regional
Government of Skane and Vasterbotten; Cancer Research UK; UK Medical
Research Council; Danish Cancer Society; Italian Association for
Research on Cancer; National Research Council Italy; HuGeF Foundation,
Torino, Italy; ISCIII RT ICC Red Tematica de Investigacion Cooperativa
en Cancer, Spain [R06/0020]; Hellenic Health Foundation; Stavros
Niarchos Foundation; Hellenic Ministry of Health and Social Solidarity
FX This research was funded in part by intramural funds from the National
Institutes of Health, Bethesda, Maryland. The Swedish Case-Control Study
acknowledges the support of the European Research Council Advanced Grant
ERC-2011-294576. The Institute of Cancer Research acknowledges National
Health Service funding to the National Institute for Health Research
Biomedical Research Centre. The principle investigators and funders
corresponding to each of the EPIC centers that contributed cases were
Heiner Boeing, Rudolph Kaaks (Germany); Goran Hallmans, Jonas Manjer
(Sweden); Timothy Key, Nick Wareham (UK); Kim Overvad, Anne Tjonneland
(Denmark); Domenico Palli, Paolo Vineis, Rosario Tumino (Italy); Maria
Jose Sanchez (Spain); Antonia Trichopoulou (Greece); from the Deutsche
Krebshilfe, Deutsches Krebsforschungszentrum and the Federal Ministry of
Education and Research Germany; the Swedish Cancer Society, Swedish
Scientific Council and the Regional Government of Skane and
Vasterbotten; Cancer Research UK and the UK Medical Research Council;
Danish Cancer Society; Italian Association for Research on Cancer,
National Research Council Italy, and HuGeF Foundation, Torino, Italy;
ISCIII RT ICC Red Tematica de Investigacion Cooperativa en Cancer
(R06/0020) Spain; Hellenic Health Foundation, the Stavros Niarchos
Foundation and the Hellenic Ministry of Health and Social Solidarity.
NR 53
TC 28
Z9 28
U1 1
U2 14
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD MAR
PY 2014
VL 106
IS 3
AR djt465
DI 10.1093/jnci/djt465
PG 11
WC Oncology
SC Oncology
GA AF4NY
UT WOS:000334691200012
PM 24552677
ER
PT J
AU Borges, S
Chen, YF
Laughren, TP
Temple, R
Patel, HD
David, PA
Mathis, M
Unger, E
Yang, PL
Khin, NA
AF Borges, Silvana
Chen, Yeh-Fong
Laughren, Thomas P.
Temple, Robert
Patel, Hiren D.
David, Paul A.
Mathis, Mitchell
Unger, Ellis
Yang, Peiling
Khin, Ni A.
TI Review of Maintenance Trials for Major Depressive Disorder: A 25-Year
Perspective From the US Food and Drug Administration
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Review
ID RELAPSE PREVENTION; RESIDUAL SYMPTOMS; METAANALYSIS; ANTIDEPRESSANTS;
RECURRENCE; REMISSION; RECOVERY
AB Objective: The maintenance efficacy of antidepressants is usually assessed in postmarketing studies with a randomized withdrawal design. This report explores differences in relapse rates, trial characteristics, and success rates in maintenance efficacy studies submitted to the US Food and Drug Administration (FDA) over a 25-year period.
Data Sources: Clinical data from all maintenance trials with antidepressants submitted to FDA between 1987 and 2012.
Study Selection: Efficacy data were compiled from 15 maintenance clinical trials in adults diagnosed with major depressive disorder according to DSM-III or DSM-IV criteria. Data Extraction: Trial characteristics, relapse rates, and time to relapse in each study were examined.
Results: Relapse rates were significantly lower (P <.05) in the drug arm than in the placebo arm in every study, with a mean relapse rate difference of 18% and an average percent reduction in relapse rate of 52% compared to placebo. Only 6% of the relapse events occurred in the first 2 weeks of the doubleblind phase. The separation between treatment arms continued to increase throughout the double-blind phase only in the trial with longest response stabilization period.
Conclusions: Antidepressant maintenance trials have a high rate of success, indicating a benefit of continuing drug treatment after initial response to an antidepressant. This benefit appears to result mainly from a decreased rate of recurrent depression rather than from an effect of drug withdrawal in the placebo groups.
C1 [Borges, Silvana; Patel, Hiren D.; David, Paul A.; Mathis, Mitchell] Food & Drug Adm 1, Div Psychiat Prod, Off New Drugs, Silver Spring, MD 20993 USA.
[Temple, Robert] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Laughren, Thomas P.] Massachusetts Gen Hosp, Clin Trials Network & Inst, Boston, MA USA.
[Laughren, Thomas P.] NIMH, Bethesda, MD 20892 USA.
RP Borges, S (reprint author), Food & Drug Adm, Div Psychiat Prod, 10903 New Hampshire Ave,Bldg 22,Rm 4159, Silver Spring, MD 20993 USA.
EM silvana.borges@fda.hhs.gov
NR 24
TC 17
Z9 17
U1 4
U2 11
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA
SN 0160-6689
EI 1555-2101
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD MAR
PY 2014
VL 75
IS 3
BP 205
EP 214
DI 10.4088/JCP.13r08722
PG 10
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA AF0RP
UT WOS:000334422000005
PM 24717376
ER
PT J
AU Yucel, MA
Selb, J
Cooper, RJ
Boas, DA
AF Yuecel, Meryem A.
Selb, Juliette
Cooper, Robert J.
Boas, David A.
TI Targeted principle component analysis: A new motion artifact correction
approach for near-infrared spectroscopy
SO JOURNAL OF INNOVATIVE OPTICAL HEALTH SCIENCES
LA English
DT Article
DE Wavelet; spline; collodion-fixed fiber
ID CEREBRAL OXYGENATION; BRAIN; TOPOGRAPHY; ACTIVATION
AB As near-infrared spectroscopy (NIRS) broadens its application area to different age and disease groups, motion artifacts in the NIRS signal due to subject movement is becoming an important challenge. Motion artifacts generally produce signal fluctuations that are larger than physiological NIRS signals, thus it is crucial to correct for them before obtaining an estimate of stimulus evoked hemodynamic responses. There are various methods for correction such as principle component analysis (PCA), wavelet-based filtering and spline interpolation. Here, we introduce a new approach to motion artifact correction, targeted principle component analysis (tPCA), which incorporates a PCA filter only on the segments of data identified as motion artifacts. It is expected that this will overcome the issues of filtering desired signals that plagues standard PCA filtering of entire data sets. We compared the new approach with the most effective motion artifact correction algorithms on a set of data acquired simultaneously with a collodion-fixed probe (low motion artifact content) and a standard Velcro probe (high motion artifact content). Our results show that tPCA gives statistically better results in recovering hemodynamic response function (HRF) as compared to wavelet-based filtering and spline interpolation for the Velcro probe. It results in a significant reduction in mean-squared error (MSE) and significant enhancement in Pearson's correlation coefficient to the true HRF. The collodion-fixed fiber probe with no motion correction performed better than the Velcro probe corrected for motion artifacts in terms of MSE and Pearson's correlation coefficient. Thus, if the experimental study permits, the use of a collodion-fixed fiber probe may be desirable. If the use of a collodion-fixed probe is not feasible, then we suggest the use of tPCA in the processing of motion artifact contaminated data.
C1 [Yuecel, Meryem A.; Selb, Juliette; Boas, David A.] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp,Dept Radiol, Charlestown, MA USA.
[Cooper, Robert J.] UCL, Dept Med Phys & Bioengn, London, England.
RP Yucel, MA (reprint author), Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp,Dept Radiol, Charlestown, MA USA.
EM mayucel@nmr.mgh.harvard.edu
OI Cooper, Robert/0000-0001-6696-8020
FU NIH [P41-RR14075]
FX This work was supported by NIH grant P41-RR14075.
NR 24
TC 8
Z9 8
U1 2
U2 11
PU WORLD SCIENTIFIC PUBL CO PTE LTD
PI SINGAPORE
PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE
SN 1793-5458
EI 1793-7205
J9 J INNOV OPT HEAL SCI
JI J. Innov. Opt. Health Sci.
PD MAR
PY 2014
VL 7
IS 2
SI SI
AR 1350066
DI 10.1142/S1793545813500661
PG 8
WC Optics; Radiology, Nuclear Medicine & Medical Imaging
SC Optics; Radiology, Nuclear Medicine & Medical Imaging
GA AF3HW
UT WOS:000334603700011
ER
PT J
AU Mar, BG
Bullinger, LB
McLean, KM
Grauman, PV
Harris, MH
Stevenson, K
Neuberg, DS
Sinha, AU
Sallan, SE
Silverman, LB
Kung, AL
Lo Nigro, L
Ebert, BL
Armstrong, SA
AF Mar, Brenton G.
Bullinger, Lars B.
McLean, Kathleen M.
Grauman, Peter V.
Harris, Marian H.
Stevenson, Kristen
Neuberg, Donna S.
Sinha, Amit U.
Sallan, Stephen E.
Silverman, Lewis B.
Kung, Andrew L.
Lo Nigro, Luca
Ebert, Benjamin L.
Armstrong, Scott A.
TI Mutations in epigenetic regulators including SETD2 are gained during
relapse in paediatric acute lymphoblastic leukaemia
SO NATURE COMMUNICATIONS
LA English
DT Article
ID DNA MISMATCH REPAIR; GENES; RESISTANCE; NT5C2; CELLS
AB Relapsed paediatric acute lymphoblastic leukaemia (ALL) has high rates of treatment failure. Epigenetic regulators have been proposed as modulators of chemoresistance, here, we sequence genes encoding epigenetic regulators in matched diagnosis-remission-relapse ALL samples. We find significant enrichment of mutations in epigenetic regulators at relapse with recurrent somatic mutations in SETD2, CREBBP, MSH6, KDM6A and MLL2, mutations in signalling factors are not enriched. Somatic alterations in SETD2, including frameshift and nonsense mutations, are present at 12% in a large de novo ALL patient cohort. We conclude that the enrichment of mutations in epigenetic regulators at relapse is consistent with a role in mediating therapy resistance.
C1 [Mar, Brenton G.; McLean, Kathleen M.; Sallan, Stephen E.; Silverman, Lewis B.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA.
[Mar, Brenton G.; Sallan, Stephen E.; Silverman, Lewis B.] Boston Childrens Hosp, Dept Hematol Oncol, Boston, MA 02115 USA.
[Bullinger, Lars B.] Univ Ulm, Dept Internal Med 3, D-89081 Ulm, Germany.
[Grauman, Peter V.; Ebert, Benjamin L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol,Dept Med, Boston, MA 02115 USA.
[Harris, Marian H.] Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Stevenson, Kristen; Neuberg, Donna S.] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Sinha, Amit U.; Armstrong, Scott A.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
[Sinha, Amit U.; Armstrong, Scott A.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10065 USA.
[Kung, Andrew L.] Columbia Univ, Med Ctr, Dept Pediat, New York, NY 10032 USA.
[Lo Nigro, Luca] Azienda Policlin OVE, I-95125 Catania, Italy.
RP Armstrong, SA (reprint author), Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
EM armstros@mskcc.org
OI Kung, Andrew/0000-0002-9091-488X; Mar, Brenton/0000-0002-3857-9324
FU National Institutes of Health [5T32CA136432-03, CA140575, CA068484];
Lady Tata Memorial Trust; William Lawrence and Blanche Hughes
Foundation; Abraham Fellowship Fund; Friends of Dana Farber; Charles H.
Hood Foundation; Leukemia and Lymphoma Society
FX We are grateful to C. Lindsley, S. Jaiswal, A. Krivtsov, M. Correll, R.
Rubio, F. Abderazzaq and Y. Wang for technical advice and valuable
discussions. We would also like to thank S. Hunt, E. Swaim, J. Allen, H.
Wang and A. Lack for assistance in obtaining clinical specimens. B. G.
M. was supported by the National Institutes of Health (5T32CA136432-03),
the Lady Tata Memorial Trust, the William Lawrence and Blanche Hughes
Foundation, the Abraham Fellowship Fund and the Friends of Dana Farber.
Additional research support was provided by the National Institutes of
Health (CA140575 and CA068484), the Charles H. Hood Foundation and the
Leukemia and Lymphoma Society.
NR 17
TC 42
Z9 43
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD MAR
PY 2014
VL 5
AR 3469
DI 10.1038/ncomms4469
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE9CA
UT WOS:000334300400052
PM 24662245
ER
PT J
AU Lehavot, K
Stappenbeck, CA
Luterek, JA
Kaysen, D
Simpson, TL
AF Lehavot, Keren
Stappenbeck, Cynthia A.
Luterek, Jane A.
Kaysen, Debra
Simpson, Tracy L.
TI Gender Differences in Relationships Among PTSD Severity, Drinking
Motives, and Alcohol Use in a Comorbid Alcohol Dependence and PTSD
Sample
SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS
LA English
DT Article
DE alcohol dependence; posttraumatic stress disorder; dual diagnosis;
drinking motives; gender differences
ID POSTTRAUMATIC-STRESS-DISORDER; NATIONALLY REPRESENTATIVE SAMPLE; SEXUAL
ASSAULT SURVIVORS; DSM-IV ALCOHOL; PSYCHIATRIC-DISORDERS; UNITED-STATES;
SUBSTANCE USE; PSYCHOMETRIC PROPERTIES; VULNERABILITY MODEL; ANXIETY
DISORDERS
AB Alcohol dependence (AD) and posttraumatic stress disorder (PTSD) are highly prevalent and comorbid conditions associated with a significant level of impairment. Little systematic study has focused on gender differences specific to individuals with both AD and PTSD. The current study examined gender-specific associations between PTSD symptom severity, drinking to cope (i.e., reduce negative affect), drinking for enhancement (i.e., increase positive affect), and average alcohol use in a clinical sample of men (n = 46) and women (n = 46) with comorbid AD and PTSD. Results indicated that PTSD symptoms were highly associated with drinking-to-cope motives for both men and women, but with greater drinking for enhancement motives for men only. Enhancement motives were positively associated with average alcohol quantity for both men and women, but coping motives were significantly associated with average alcohol quantity for women only. These findings suggest that for individuals with comorbid AD and PTSD, interventions that focus on reducing PTSD symptoms are likely to lower coping motives for both genders, and targeting coping motives is likely to result in decreased drinking for women but not for men, whereas targeting enhancement motives is likely to lead to reduced drinking for both genders.
C1 [Lehavot, Keren] VA Puget Sound Hlth Care Syst, Adv Fellowship Program Mental Illness Res & Treat, Seattle, WA USA.
[Lehavot, Keren; Stappenbeck, Cynthia A.; Luterek, Jane A.; Kaysen, Debra; Simpson, Tracy L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Luterek, Jane A.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, Ctr Excellence Subs Abuse Treatment & Educ, Seattle, WA USA.
RP Lehavot, K (reprint author), 1660 S Columbian Way, Seattle, WA 98108 USA.
EM klehavot@uw.edu
FU NIAAA NIH HHS [R21 AA017130]
NR 78
TC 15
Z9 15
U1 5
U2 8
PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA
SN 0893-164X
EI 1939-1501
J9 PSYCHOL ADDICT BEHAV
JI Psychol. Addict. Behav.
PD MAR
PY 2014
VL 28
IS 1
BP 42
EP 52
DI 10.1037/a0032266
PG 11
WC Substance Abuse; Psychology, Multidisciplinary
SC Substance Abuse; Psychology
GA AF4OR
UT WOS:000334693600005
PM 23647151
ER
PT J
AU Kaysen, D
Atkins, DC
Simpson, TL
Stappenbeck, CA
Blayney, JA
Lee, CM
Larimer, ME
AF Kaysen, Debra
Atkins, David C.
Simpson, Tracy L.
Stappenbeck, Cynthia A.
Blayney, Jessica A.
Lee, Christine M.
Larimer, Mary E.
TI Proximal Relationships Between PTSD Symptoms and Drinking Among Female
College Students: Results From a Daily Monitoring Study
SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS
LA English
DT Article
DE posttraumatic stress disorder; PTSD; college students; victimization;
alcohol use
ID POSTTRAUMATIC-STRESS-DISORDER; ALCOHOL-USE DISORDERS; SEXUAL EXPERIENCES
SURVEY; SUBSTANCE USE; SELF-MEDICATION; BINGE DRINKING; YOUNG-ADULTS;
ATTENDING PEERS; NEGATIVE AFFECT; WITHIN-PERSON
AB Self-medication has been theorized to explain comorbidity between posttraumatic stress disorder (PTSD) and drinking, whereupon problem drinking develops in order to modulate negative affect and ameliorate PTSD symptoms. Daily monitoring methodologies may help refine our understanding of proximal relations between PTSD, affect, and alcohol use. One hundred thirty-six female college drinkers with a past history of sexual victimization and 38 female college drinkers with no past trauma history completed electronic monitoring of PTSD symptoms, affect, alcohol use, and alcohol cravings, daily for 4 weeks. A two-part mixed hurdle model was used to examine likelihood of drinking and amount of alcohol consumed on drinking days. We found significant relationships between daily PTSD symptoms, affect, and drinking. On days women experienced more intrusive and behavioral avoidance symptoms of PTSD, they experienced stronger urges to drink and were more likely to drink on that day. On days in which women experienced more negative affect than their average, they experienced stronger urges to drink, whereas on days in which women experienced more of the dysphoric symptoms associated with PTSD than their average, they drank less. On days with higher positive affect, women reported stronger urges to drink and were more likely to drink. Results suggest the need to examine both aspects of affect and specific PTSD symptoms as they may differentially predict drinking behavior. Differences in the ways in which PTSD symptoms and affect influence drinking suggest that interventions more specifically address the function of drinking behaviors in reducing alcohol use among college women.
C1 [Kaysen, Debra; Atkins, David C.; Stappenbeck, Cynthia A.; Blayney, Jessica A.; Lee, Christine M.; Larimer, Mary E.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Kaysen, Debra; Larimer, Mary E.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA.
[Kaysen, Debra] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
[Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
RP Kaysen, D (reprint author), Dept Psychiat & Behav Sci, 1100 NE 45th St,Suite 300,UW Box 354944, Seattle, WA 98195 USA.
EM dkaysen@u.washington.edu
OI Atkins, David/0000-0002-5781-9880
FU NIAAA NIH HHS [R01 AA020252, R01AA020252, R21 AA016211, R21AA016211, T32
AA007455, T32AA007455]
NR 89
TC 21
Z9 21
U1 5
U2 12
PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA
SN 0893-164X
EI 1939-1501
J9 PSYCHOL ADDICT BEHAV
JI Psychol. Addict. Behav.
PD MAR
PY 2014
VL 28
IS 1
BP 62
EP 73
DI 10.1037/a0033588
PG 12
WC Substance Abuse; Psychology, Multidisciplinary
SC Substance Abuse; Psychology
GA AF4OR
UT WOS:000334693600007
PM 23915369
ER
PT J
AU Tsai, AG
Hosokawa, P
Schoen, J
Prochazka, AV
AF Tsai, Adam G.
Hosokawa, Patrick
Schoen, Jonathan
Prochazka, Allan V.
TI Frequency of laboratory testing among gastric bypass patients
SO SURGERY FOR OBESITY AND RELATED DISEASES
LA English
DT Article
DE Bariatric surgery; Obesity surgery; Quality of care; Nutrition
assessment; Clinical care
ID NUTRITIONAL DEFICIENCIES; VITAMIN DEFICIENCY; BARIATRIC SURGERY
AB Background: Long-term laboratory monitoring is recommended. after gastric bypass surgery to prevent the development of micronutrient deficiencies. The objective of this study was to characterize patterns of laboratory monitoring after surgery.
Methods: We used a large insurance claims database to assess the frequency of laboratory testing after gastric bypass surgery. We assessed the tests recommended by an expert panel on bariatric surgery, including tests recommended routinely as well as second-line tests for specific clinical scenarios (e.g., tests for anemia when iron deficiency is not present).
Results: With the exception of testing for diabetes, most gastric bypass patients did not undergo routine laboratory testing in the first year after their surgery, ranging from 54% (electrolytes) to 95% (zinc). However, for first-line tests, significantly more gastric bypass patients underwent testing in the first year,compared with gastric banding patients. Differences in testing frequency between gastric bypass and gastric banding patients were larger for tests of micronutrient deficiency than for common metabolic panels and complete blood counts. For second-line tests, much smaller percentages of both groups of patients underwent testing, either in the first year or after year 1.
Conclusion: Patients undergoing gastric bypass do not routinely undergo recommended laboratory tests, although they are undergoing more monitoring than gastric banding patients. Efforts must be made by patients, surgeons, and primary care providers to ensure that routine testing is done to lower the risk of adverse health outcomes. (Surg Obes Relat Dis 2014;10:340-347.) (C) 2014 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.
C1 [Tsai, Adam G.; Prochazka, Allan V.] Univ Colorado, Div Gen Internal Med, Aurora, CO 80045 USA.
[Tsai, Adam G.] Univ Colorado, Anschutz Ctr Hlth & Wellness, Aurora, CO 80045 USA.
[Hosokawa, Patrick] Univ Colorado, Colorado Hlth Outcomes Program, Aurora, CO 80045 USA.
[Schoen, Jonathan] Univ Colorado, Dept Surg, Aurora, CO 80045 USA.
[Prochazka, Allan V.] Denver VA Med Ctr, Denver, CO USA.
RP Tsai, AG (reprint author), Univ Colorado, Sch Med, Anschutz Hlth & Wellness Bldg, Aurora, CO 80045 USA.
EM adam.tsai@ucdenver.edu
NR 17
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 1550-7289
EI 1878-7533
J9 SURG OBES RELAT DIS
JI Surg. Obes. Relat. Dis.
PD MAR-APR
PY 2014
VL 10
IS 2
BP 340
EP 345
DI 10.1016/j.soard.2013.09.005
PG 6
WC Surgery
SC Surgery
GA AF3XW
UT WOS:000334647000029
PM 24355327
ER
PT J
AU Gunel, C
Feldman, RE
Bleier, BS
AF Gunel, Ceren
Feldman, Rachel E.
Bleier, Benjamin S.
TI Osteitis is associated with P-glycoprotein overexpression in patients
with chronic sinusitis without nasal polyps
SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY
LA English
DT Article
ID COMPUTED TOMOGRAPHIC FINDINGS; CHRONIC RHINOSINUSITIS; EOSINOPHILIA;
INFLAMMATION; MARKER; EXPRESSION; SURGERY; ASTHMA; BONE
AB Background: P-glycoprotein (P-gp) is a membrane-bound efflux pump that is up-regulated in eosinophilic chronic rhinosinusitis and participates in epithelial cytokine secretion. Osteitis is associated with eosinophilic inflammation and may represent a method to predict patients with P-gp overexpression. The purpose of this article was to determine whether P-gp overexpression and increased osteitis scores are associated in patients with chronic rhinosinusitis (CRS).
Methods: An Institutional Review Board-approved study was performed using sinus tissue in 38 patients with CRS. P-gp expression was calculated using quantitative fluorescent immunohistochemistry to generate an epithelial-to-background staining ratio. Patients were stratified into low and high P-gp expression groups. Osteitis was scored radiologically using the Kennedy Osteitis Score (KOS) and Global Osteitis Score (GOS). Serum eosinophilia was assessed. KOS and GOS were compared using a Pearson's correlation coefficient. Osteitis scores and serum eosinophil concentrations between P-gp expression groups were compared using a nonparametric Mann-Whitney U test (two tailed).
Results: Among the 38 patients, 7(18.42%) had high P-gp expression (mean +/- SD, 4.86 +/- 1.33) whereas 31(81.57%) had low expression ratios (1.93 +/- 0.45). No patients in the high P-gp expression group had undergone prior surgery. Median serum eosinophil values were significantly greater in the high versus low P-gp expression group (6.98 +/- 2.17 versus 2.36 +/- 1.38, p < 0.001). GOS and KOS values were significantly greater in the high versus low P-gp expression group (15.86 +/- 4.91 versus 6.29 +/- 1.25 and 4.55 +/- 4.33 verus 2.23 +/- 1.71; p < 0.001). KOS and GOS values were significantly correlated (r = 0.835; p < 0.001).
Conclusion: Increased osteitis burden as measured by either the KOS or the GOS is associated with increased P-gp membranous expression in CRS. Radiographic quantification of osteitis may therefore be used to identify patients with P-gp overexpression thereby providing a novel potential therapeutic target.
C1 [Gunel, Ceren] Adnan Menderes Univ, Med Sch Hosp, Dept Otolaryngol Head & Neck Surg, TR-09100 Aytepe Mevkii, Aydin, Turkey.
[Feldman, Rachel E.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA USA.
[Bleier, Benjamin S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol Head & Neck Surg, Boston, MA USA.
RP Gunel, C (reprint author), Adnan Menderes Univ, Tip Fak, Hastanesi KBB AD, TR-09100 Aytepe Mevkii, Aydin, Turkey.
EM drgunel@hotmail.com
FU ARS
FX B Bleier was the recipient of the ARS Investigator Grant. The remaining
authors have no conflicts of interest pertaining to this article
NR 17
TC 8
Z9 8
U1 0
U2 2
PU OCEAN SIDE PUBLICATIONS INC
PI PROVIDENCE
PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA
SN 1945-8924
EI 1945-8932
J9 AM J RHINOL ALLERGY
JI Am. J. Rhinol. Allergy
PD MAR-APR
PY 2014
VL 28
IS 2
BP 99
EP 102
DI 10.2500/ajra.2014.28.4011
PG 4
WC Otorhinolaryngology
SC Otorhinolaryngology
GA AE5TL
UT WOS:000334052100009
PM 24717943
ER
PT J
AU DeYoung, K
Wentzel, JL
Schlosser, RJ
Nguyen, SA
Soler, ZM
AF DeYoung, Kristen
Wentzel, Jennifer L.
Schlosser, Rodney J.
Nguyen, Shaun A.
Soler, Zachary M.
TI Systematic review of immunotherapy for chronic rhinosinusitis
SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY
LA English
DT Review
ID ALLERGIC FUNGAL SINUSITIS; GRASS-POLLEN IMMUNOTHERAPY; SUBCUTANEOUS
IMMUNOTHERAPY; FOLLOW-UP; RHINITIS; DISEASE; ASTHMA
AB Background: Immunotherapy (IT) has been well established as an effective treatment for allergic rhinitis (AR), but little is known about the benefits of IT on clinical outcomes of comorbid chronic rhinosinusitis (CRS). The goal of this publication is to systematically review the literature regarding outcomes of IT in patients with atopic CRS.
Methods: A systematic review of the literature was conducted including studies that assessed the efficacy of IT on clinical outcome measures in CRS including without polyp, with polyp, and allergic fungal rhinosinusitis subgroups. Excluded articles were those only reporting outcomes specific to asthma or AR.
Results: Seven studies met the inclusion and exclusion criteria for this review, none of which were randomized controlled trials. Generally, symptom scores improved in patients treated with IT when compared with baseline data and control patients. Objective endoscopic exam measures improved with IT treatment in short-term studies. Significant improvements were observed in radiographic assessments, and there was a decreased necessity for revision surgery, interventional office visits, and intranasal and oral steroid use.
Conclusion: Conclusions are limited by the paucity of available data on the efficacy of IT for treating CRS-specific outcome measures. There is weak evidence to support the use of IT as an adjunctive treatment in CRS patients, particularly in the postoperative period.
C1 [DeYoung, Kristen; Wentzel, Jennifer L.; Schlosser, Rodney J.; Nguyen, Shaun A.; Soler, Zachary M.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA.
[Schlosser, Rodney J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
RP Soler, ZM (reprint author), Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, 135 Rutledge Ave,MSC 550, Charleston, SC 29425 USA.
EM solerz@musc.edu
NR 24
TC 9
Z9 10
U1 1
U2 5
PU OCEAN SIDE PUBLICATIONS INC
PI PROVIDENCE
PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA
SN 1945-8924
EI 1945-8932
J9 AM J RHINOL ALLERGY
JI Am. J. Rhinol. Allergy
PD MAR-APR
PY 2014
VL 28
IS 2
BP 145
EP 150
DI 10.2500/ajra.2014.28.4019
PG 6
WC Otorhinolaryngology
SC Otorhinolaryngology
GA AE5TL
UT WOS:000334052100017
PM 24717953
ER
PT J
AU Mainwaring, P
Yu, EY
Londhe, A
Van Poppel, H
Rathkopf, DE
Smith, MR
Souza, P
Griffin, TW
Ryan, CJ
AF Mainwaring, P.
Yu, E. Y.
Londhe, A.
Van Poppel, H.
Rathkopf, D. E.
Smith, M. R.
Souza, P.
Griffin, T. W.
Ryan, C. J.
CA Study COU-AA-302 Investigators
TI Association of alkaline phosphatase with clinical outcomes in
chemotherapy-naive metastatic castration-resistant prostate cancer
(mCRPC): results from COU-AA-302
SO BJU INTERNATIONAL
LA English
DT Meeting Abstract
CT 67th Annual Scientific Meeting of the
Urological-Society-of-Australia-and-New-Zealand
CY MAR 16-19, 2014
CL Brisbane, AUSTRALIA
SP Urol Soc Australia & New Zealand
C1 [Mainwaring, P.] Hematol & Oncol Clin Australia, Brisbane, Qld, Australia.
[Yu, E. Y.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Londhe, A.] Janssen Res & Dev LLC, Raritan, NJ USA.
[Van Poppel, H.] Katholieke Univ Leuven Hosp, Louvain, Belgium.
[Rathkopf, D. E.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Rathkopf, D. E.] Weill Cornell Med Coll, New York, NY USA.
[Smith, M. R.] Harvard Univ, Sch Med, Boston, MA USA.
[Smith, M. R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Souza, P.] Univ Western Sydney, Sch Med, Sydney, NSW, Australia.
[Griffin, T. W.] Janssen Res & Dev, Los Angeles, CA USA.
[Ryan, C. J.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 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 1464-4096
EI 1464-410X
J9 BJU INT
JI BJU Int.
PD MAR
PY 2014
VL 113
SU 4
MA 41
BP 21
EP 21
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA AB2DB
UT WOS:000331602100042
ER
PT J
AU Pittman, K
Smith, M
Coleman, R
Klotz, L
Milecki, P
Wei, R
Balakumaran, A
Fizazi, K
AF Pittman, K.
Smith, M.
Coleman, R.
Klotz, L.
Milecki, P.
Wei, R.
Balakumaran, A.
Fizazi, K.
TI Denosumab for the prevention of symptomatic skeletal events in patients
with castration-resistant advanced prostate cancer: a comparison with
skeletal-related events
SO BJU INTERNATIONAL
LA English
DT Meeting Abstract
CT 67th Annual Scientific Meeting of the
Urological-Society-of-Australia-and-New-Zealand
CY MAR 16-19, 2014
CL Brisbane, AUSTRALIA
SP Urol Soc Australia & New Zealand
C1 [Pittman, K.] Queen Elizabeth Hosp, Woodville, SA 5011, Australia.
[Smith, M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Coleman, R.] Weston Pk Hosp, Acad Unit Clin Oncol, Sheffield, S Yorkshire, England.
[Klotz, L.] Sunnybrook & Womens Coll, Hlth Sci Ctr, Toronto, ON, Canada.
[Milecki, P.] Wielkopolskie Ctr Onkol, Poznan, Poland.
[Wei, R.; Balakumaran, A.] Amgen Inc, Thousand Oaks, CA 91320 USA.
[Fizazi, K.] Univ Paris Sud, Inst Gustave Roussy, Paris, France.
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 1464-4096
EI 1464-410X
J9 BJU INT
JI BJU Int.
PD MAR
PY 2014
VL 113
SU 4
MA 46
BP 23
EP 23
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA AB2DB
UT WOS:000331602100047
ER
PT J
AU Marx, G
Patrick, D
Cleeland, C
Fallowfield, L
Smith, M
Klotz, L
Oudard, S
Wei, R
Ohrling, K
Qian, Y
AF Marx, G.
Patrick, D.
Cleeland, C.
Fallowfield, L.
Smith, M.
Klotz, L.
Oudard, S.
Wei, R.
Ohrling, K.
Qian, Y.
TI Denosumab or zoledronic acid therapy on pain interference and
cancer-specific quality of life in patients with castrate-resistant
prostate cancer and bone metastases
SO BJU INTERNATIONAL
LA English
DT Meeting Abstract
CT 67th Annual Scientific Meeting of the
Urological-Society-of-Australia-and-New-Zealand
CY MAR 16-19, 2014
CL Brisbane, AUSTRALIA
SP Urol Soc Australia & New Zealand
C1 [Marx, G.] Sydney Adventist Hosp, Integrated Canc Ctr, Wahroonga, Australia.
[Patrick, D.] Univ Washington, Seattle, WA 98195 USA.
[Cleeland, C.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Fallowfield, L.] Univ Sussex, Sussex Hlth Outcomes Res & Educ Canc SHORE C, Brighton, E Sussex, England.
[Smith, M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Klotz, L.] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada.
[Oudard, S.] European Georges Popidou Hosp, Paris, France.
[Wei, R.; Ohrling, K.; Qian, Y.] Amgen Inc, Thousand Oaks, CA 91320 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1464-4096
EI 1464-410X
J9 BJU INT
JI BJU Int.
PD MAR
PY 2014
VL 113
SU 4
MA 47
BP 24
EP 24
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA AB2DB
UT WOS:000331602100048
ER
PT J
AU Wirth, LJ
AF Wirth, Lori J.
TI Chemoprevention of Squamous Cell Carcinoma of the Head and Neck: No Time
to Lose Momentum
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID ORAL PREMALIGNANT LESIONS; PHASE IIB TRIAL; CYCLIN D1;
HUMAN-PAPILLOMAVIRUS; RANDOMIZED-TRIAL; PRIMARY TUMORS; UNITED-STATES;
HPV INFECTION; CANCER; LEUKOPLAKIA
AB The prospects for chemoprevention to reduce the incidence of squamous cell carcinoma of the head and neck (SCCHN) are great. The tissue at risk for harboring disease is relatively accessible for examination and biopsy. Patients appropriate for study can be easily identified by their risk factors and the presence of premalignant lesions. Our understanding of the pathogenesis of SCCHN is ever increasing, and offers new opportunities to explore strategies for prevention therapies. In this issue of Cancer Prevention Research, Saba and colleagues report on a phase Ib trial of celecoxib plus erlotinib to prevent progression to higher-grade dysplasia or invasive carcinoma in patients with oral premalignant lesions. The overall response rate was 57%, though by the time of last analysis, 85% of patients relapsed. In this commentary, challenges to the success of chemoprevention clinical trials for SCCHN, such as pitfalls in using surrogate biomarkers and reversal of histologic premalignant changes as study endpoints, are discussed. In addition, strategies to help ensure further development in the field of head and neck cancer prevention are reviewed. These include focusing efforts on tobacco cessation and human papillomavirus vaccination, targeting key molecular drivers of head and neck carcinogenesis, and focusing on combination strategies that have the potential to eradicate premalignant clones, even if some toxicity is encountered. (C) 2014 AACR.
C1 [Wirth, Lori J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
RP Wirth, LJ (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA.
EM lwirth@partners.org
NR 37
TC 2
Z9 2
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
EI 1940-6215
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD MAR
PY 2014
VL 7
IS 3
BP 279
EP 282
DI 10.1158/1940-6207.CAPR-13-0437
PG 4
WC Oncology
SC Oncology
GA AE5UW
UT WOS:000334055800001
PM 24441671
ER
PT J
AU Choi, SE
Perzan, KE
Tramontano, AC
Kong, CY
Hur, C
AF Choi, Sung Eun
Perzan, Katherine E.
Tramontano, Angela C.
Kong, Chung Yin
Hur, Chin
TI Statins and Aspirin for Chemoprevention in Barrett's Esophagus: Results
of a Cost-Effectiveness Analysis
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID HIGH-GRADE DYSPLASIA; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; EXTENDED
TRANSTHORACIC RESECTION; GASTROESOPHAGEAL-REFLUX DISEASE;
CORONARY-HEART-DISEASE; PRIMARY PREVENTION; RADIOFREQUENCY ABLATION;
RANDOMIZED-TRIALS; CANCER-RISK; ADENOCARCINOMA
AB Data suggest that aspirin, statins, or a combination of the two drugs may lower the progression of Barrett's esophagus to esophageal adenocarcinoma. However, aspirin is associated with potential complications such as gastrointestinal bleeding and hemorrhagic stroke, and statins are associated with myopathy. We developed a simulation disease model to study the effectiveness and cost effectiveness of aspirin and statin chemoprevention against esophageal adenocarcinoma. A decision analytic Markov model was constructed to compare four strategies for Barrett's esophagus management; all regimens included standard endoscopic surveillance regimens: (i) endoscopic surveillance alone, (ii) aspirin therapy, (iii) statin therapy, and (iv) combination therapy of aspirin and statin. Endpoints evaluated were life expectancy, quality-adjusted life years (QALY), costs, and incremental cost-effectiveness ratios (ICER). Sensitivity analysis was performed to determine the impact of model input uncertainty on results. Assuming an annual progression rate of 0.33% per year from Barrett's esophagus to esophageal adenocarcinoma, aspirin therapy was more effective and cost less than (dominated) endoscopic surveillance alone. When combination therapy was compared with aspirin therapy, the ICER was $ 158,000/QALY, which was above our willingness-to-pay threshold of $ 100,000/QALY. Statin therapy was dominated by combination therapy. When higher annual cancer progression rates were assumed in the model (0.5% per year), combination therapy was cost-effective compared with aspirin therapy, producing an ICER of $ 96,000/QALY. In conclusion, aspirin chemoprevention was both more effective and cost less than endoscopic surveillance alone. Combination therapy using both aspirin and statin is expensive but could be cost-effective in patients at higher risk of progression to esophageal adenocarcinoma. (C) 2013 AACR.
C1 [Choi, Sung Eun; Perzan, Katherine E.; Tramontano, Angela C.; Kong, Chung Yin; Hur, Chin] Inst Technol Assessment, Boston, MA USA.
[Perzan, Katherine E.; Hur, Chin] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Kong, Chung Yin; Hur, Chin] Harvard Univ, Sch Med, Boston, MA USA.
RP Hur, C (reprint author), Massachusetts Gen Hosp, 101 Merrimac St,10th Floor, Boston, MA 02114 USA.
EM chur@partners.org
OI Hur, Chin/0000-0002-2819-7576
FU NIH [R01-CA140574, U01-CA152926, K25-CA133141]
FX This study was supported by NIH grants R01-CA140574 and U01-CA152926 (to
C. Hur) and K25-CA133141 (to C.Y. Kong)
NR 58
TC 8
Z9 8
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
EI 1940-6215
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD MAR
PY 2014
VL 7
IS 3
BP 341
EP 350
DI 10.1158/1940-6207.CAPR-13-0191-T
PG 10
WC Oncology
SC Oncology
GA AE5UW
UT WOS:000334055800008
PM 24380852
ER
PT J
AU Scaglia, N
Tyekucheva, S
Zadra, G
Photopoulos, C
Loda, M
AF Scaglia, Natalia
Tyekucheva, Svitlana
Zadra, Giorgia
Photopoulos, Cornelia
Loda, Massimo
TI De novo fatty acid synthesis at the mitotic exit is required to complete
cellular division
SO CELL CYCLE
LA English
DT Article
DE de novo lipogenesis; phospholipid; fatty acid; cell cycle; cell cycle
arrest; AMPK; metabolome; lysophospholipid; C75
ID CTP-PHOSPHOCHOLINE CYTIDYLYLTRANSFERASE; ACETYL-COA CARBOXYLASE;
CTPPHOSPHOCHOLINE CYTIDYLYLTRANSFERASE; PHOSPHOLIPID-METABOLISM;
ENDOPLASMIC-RETICULUM; CYCLE REGULATION; CANCER-THERAPY; LIFE-CYCLE;
MAST CELLS; S-PHASE
AB Although the regulation of the cell cycle has been extensively studied, much less is known about its coordination with the cellular metabolism. Using mass spectrometry we found that lysophospholipid levels decreased drastically from G(2)/M to G(1) phase, while de novo phosphatidylcholine synthesis, the main phospholipid in mammalian cells, increased, suggesting that enhanced membrane production was concomitant to a decrease in its turnover. In addition, fatty acid synthesis and incorporation into membranes was increased upon cell division. The rate-limiting reaction for de novo fatty acid synthesis is catalyzed by acetyl-CoA carboxylase. As expected, its inhibiting phosphorylation decreased prior to cytokinesis initiation. Importantly, the inhibition of fatty acid synthesis arrested the cells at G(2)/M despite the presence of abundant fatty acids in the media. Our results suggest that de novo lipogenesis is essential for cell cycle completion. This "lipogenic checkpoint" at G(2)/M may be therapeutically exploited for hyperproliferative diseases such as cancer.
C1 [Scaglia, Natalia; Zadra, Giorgia; Photopoulos, Cornelia; Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Tyekucheva, Svitlana] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Tyekucheva, Svitlana] Harvard Univ, Sch Med, Dept Biostat, Boston, MA 02115 USA.
[Zadra, Giorgia; Loda, Massimo] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA.
[Loda, Massimo] Broad Inst, Cambridge, MA USA.
[Loda, Massimo] Kings Coll London, Div Canc Studies, London WC2R 2LS, England.
RP Loda, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
EM massimo_loda@dfci.harvard.edu
FU Prostate Cancer Foundation; DF/HCC SPORE in Prostate Cancer [NIH/NCI P50
CA90381]; NIH [RO1CA131945]; Nuclea Biomarkers (Pittsfield, MA)
FX We are in debt to Dr Lesley Wassef for critical review of the manuscript
and Maria Elina Scaglia for her help with the figures. This work was
supported by the Prostate Cancer Foundation, the DF/HCC SPORE in
Prostate Cancer (NIH/NCI P50 CA90381), NIH grant RO1CA131945, and
philanthropic funds from Nuclea Biomarkers (Pittsfield, MA) to M.L.
NR 57
TC 12
Z9 12
U1 2
U2 11
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
EI 1551-4005
J9 CELL CYCLE
JI Cell Cycle
PD MAR 1
PY 2014
VL 13
IS 5
BP 859
EP 868
DI 10.4161/cc.27767
PG 10
WC Cell Biology
SC Cell Biology
GA AE3UQ
UT WOS:000333904200027
PM 24418822
ER
PT J
AU Oliva, E
Young, R
AF Oliva, Esther
Young, Robert H.
TI Endocrine Pathology of the Ovary
SO ENDOCRINE PATHOLOGY
LA English
DT Article
DE Ovary; Function; Endocrine; Pathology
ID SERTOLI-LEYDIG-CELL; CORD-STROMAL TUMORS; ADULT-GRANULOSA-CELL;
OF-THE-LITERATURE; ALPHA-FETOPROTEIN PRODUCTION; LUTEINIZED FOLLICLE
CYST; MCCUNE-ALBRIGHT-SYNDROME; PEUTZ-JEGHERS SYNDROME; FEMALE
GENITAL-TRACT; CLINICOPATHOLOGICAL ANALYSIS
C1 [Oliva, Esther; Young, Robert H.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp,James Homer Wright Pathol, Boston, MA 02115 USA.
[Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Oliva, E (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 219, Boston, MA 02114 USA.
EM eoliva@partners.org
NR 151
TC 1
Z9 1
U1 1
U2 1
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1046-3976
EI 1559-0097
J9 ENDOCR PATHOL
JI Endocr. Pathol.
PD MAR
PY 2014
VL 25
IS 1
BP 102
EP 119
DI 10.1007/s12022-013-9285-4
PG 18
WC Endocrinology & Metabolism; Pathology
SC Endocrinology & Metabolism; Pathology
GA AF0PH
UT WOS:000334416000014
PM 24420639
ER
PT J
AU Haun, JN
Lind, JD
Shimada, SL
Martin, TL
Gosline, RM
Antinori, N
Stewart, M
Simon, SR
AF Haun, Jolie N.
Lind, Jason D.
Shimada, Stephanie L.
Martin, Tracey L.
Gosline, Robert M.
Antinori, Nicole
Stewart, Max
Simon, Steven R.
TI Evaluating User Experiences of the Secure Messaging Tool on the Veterans
Affairs' Patient Portal System
SO JOURNAL OF MEDICAL INTERNET RESEARCH
LA English
DT Article
DE veterans; secure messaging; patient-provider communication; Department
of Veterans Affairs; usability testing; mixed methods; patient-centered
care
ID HEALTH-CARE; E-MAIL; COMMUNICATION; LITERACY; RECORDS; PERSPECTIVES;
VALIDATION; PHYSICIANS; ATTITUDES; SETTINGS
AB Background: The United States Department of Veterans Affairs has implemented an electronic asynchronous "Secure Messaging" tool within a Web-based patient portal (ie, My HealtheVet) to support patient-provider communication. This electronic resource promotes continuous and coordinated patient-centered care, but to date little research has evaluated patients' experiences and preferences for using Secure Messaging.
Objective: The objectives of this mixed-methods study were to (1) characterize veterans' experiences using Secure Messaging in the My HealtheVet portal over a 3-month period, including system usability, (2) identify barriers to and facilitators of use, and (3) describe strategies to support veterans' use of Secure Messaging.
Methods: We recruited 33 veterans who had access to and had previously used the portal's Secure Messaging tool. We used a combination of in-depth interviews, face-to-face user-testing, review of transmitted secure messages between veterans and staff, and telephone interviews three months following initial contact. We assessed participants' computer and health literacy during initial and follow-up interviews. We used a content-analysis approach to identify dominant themes in the qualitative data. We compared inferences from each of the data sources (interviews, user-testing, and message review) to identify convergent and divergent data trends.
Results: The majority of veterans (27/33, 82%) reported being satisfied with Secure Messaging at initial interview; satisfaction ratings increased to 97% (31/32, 1 missing) during follow-up interviews. Veterans noted Secure Messaging to be useful for communicating with their primary care team to manage health care needs (eg, health-related questions, test requests and results, medication refills and questions, managing appointments). Four domains emerged from interviews: (1) perceived benefits of using Secure Messaging, (2) barriers to using Secure Messaging, (3) facilitators for using Secure Messaging, and (4) suggestions for improving Secure Messaging. Veterans identified and demonstrated impediments to successful system usage that can be addressed with education, skill building, and system modifications. Analysis of secure message content data provided insights to reasons for use that were not disclosed by participants during interviews, specifically sensitive health topics such as erectile dysfunction and sexually transmitted disease inquiries.
Conclusions: Veterans perceive Secure Messaging in the My HealtheVet patient portal as a useful tool for communicating with health care teams. However, to maximize sustained utilization of Secure Messaging, marketing, education, skill building, and system modifications are needed. Data from this study can inform a large-scale quantitative assessment of Secure Messaging users' experiences in a representative sample to validate qualitative findings.
C1 [Haun, Jolie N.; Lind, Jason D.; Antinori, Nicole] James A Haley VA Med Ctr, HSR&D RR&D Ctr Innovat Disabil & Rehabil Res, Dept Vet Affairs, Tampa, FL 33637 USA.
[Haun, Jolie N.] Univ S Florida, Coll Publ Hlth, Dept Community & Family Med, Tampa, FL USA.
[Lind, Jason D.] Univ S Florida, Dept Anthropol, Tampa, FL 33620 USA.
[Shimada, Stephanie L.] Edith Nourse Rogers Mem VA Hosp, CHOIR, Dept Vet Affairs, Bedford, MA USA.
[Shimada, Stephanie L.] Edith Nourse Rogers Mem VA Hosp, Natl Ehlth Qual Enhancement Res Initiat QUERI Coo, Bedford, MA USA.
[Shimada, Stephanie L.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA.
[Shimada, Stephanie L.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Div Hlth Informat & Implementat Sci, Worcester, MA USA.
[Martin, Tracey L.] VA New England Hlth Care Syst, Dept Vet Affairs, Bedford, MA USA.
[Gosline, Robert M.] James A Haley VA Med Ctr, Dept Vet Affairs, Tampa, FL USA.
[Stewart, Max; Simon, Steven R.] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Gen Internal Med Sect, Dept Vet Affairs, Boston, MA USA.
RP Haun, JN (reprint author), James A Haley VA Med Ctr, HSR&D RR&D Ctr Innovat Disabil & Rehabil Res, Dept Vet Affairs, 8900 Grand Oak Cir 151R, Tampa, FL 33637 USA.
EM Jolie.Haun@va.gov
OI Lind, Jason/0000-0002-1610-0431
FU Department of Veterans Affairs; Veterans Health Administration; Office
of Research and Development; Health Services Research and Development
Service; National eHealth Quality Enhancement Research Initiative
(QUERI) Coordinating Center [RRP 11-397]; Center of Innovation for
Disability and Rehabilitation Research at the James A. Haley Veterans
Hospital; Center for Healthcare Organization and Implementation Research
(CHOIR)
FX The development of this manuscript was supported by the Department of
Veterans Affairs, Veterans Health Administration, Office of Research and
Development, Health Services Research and Development Service, and
National eHealth Quality Enhancement Research Initiative (QUERI)
Coordinating Center (RRP 11-397). This manuscript was also supported in
part by the Center of Innovation for Disability and Rehabilitation
Research at the James A. Haley Veterans Hospital, and the Center for
Healthcare Organization and Implementation Research (CHOIR).
NR 35
TC 16
Z9 16
U1 5
U2 16
PU JMIR PUBLICATIONS, INC
PI TORONTO
PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA
SN 1438-8871
J9 J MED INTERNET RES
JI J. Med. Internet Res.
PD MAR
PY 2014
VL 16
IS 3
BP 266
EP 281
AR e75
DI 10.2196/jmir.2976
PG 16
WC Health Care Sciences & Services; Medical Informatics
SC Health Care Sciences & Services; Medical Informatics
GA AE5IN
UT WOS:000334021200022
PM 24610454
ER
PT J
AU Kaittanis, C
Shaffer, TM
Ogirala, A
Santra, S
Perez, JM
Chiosis, G
Li, YM
Josephson, L
Grimm, J
AF Kaittanis, Charalambos
Shaffer, Travis M.
Ogirala, Anuja
Santra, Santimukul
Perez, J. Manuel
Chiosis, Gabriela
Li, Yueming
Josephson, Lee
Grimm, Jan
TI Environment-responsive nanophores for therapy and treatment monitoring
via molecular MRI quenching
SO NATURE COMMUNICATIONS
LA English
DT Article
ID DRUG-DELIVERY; MAGNETIC-RELAXATION; CANCER-THERAPY; PROSTATE-CANCER;
NANOPARTICLES; NANOSENSORS; TELOMERASE; INHIBITOR; EFFICACY; TUMORS
AB The effective delivery of therapeutics to disease sites significantly contributes to drug efficacy, toxicity and clearance. Here we demonstrate that clinically approved iron oxide nanoparticles (Ferumoxytol) can be utilized to carry one or multiple drugs. These so called 'nanophores' retain their cargo within their polymeric coating through weak electrostatic interactions and release it in slightly acidic conditions (pH 6.8 and below). The loading of drugs increases the nanophores' transverse T2 and longitudinal T1 nuclear magnetic resonance (NMR) proton relaxation times, which is proportional to amount of carried cargo. Chemotherapy with translational nanophores is more effective than the free drug in vitro and in vivo, without subjecting the drugs or the carrier nanoparticle to any chemical modification. Evaluation of cargo incorporation and payload levels in vitro and in vivo can be assessed via benchtop magnetic relaxometers, common NMR instruments or magnetic resonance imaging scanners.
C1 [Kaittanis, Charalambos; Shaffer, Travis M.; Ogirala, Anuja; Chiosis, Gabriela; Li, Yueming; Grimm, Jan] Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Chem Program, New York, NY 10065 USA.
[Shaffer, Travis M.] CUNY Hunter Coll, Grad Ctr, Dept Chem, New York, NY 10065 USA.
[Santra, Santimukul] Pittsburg State Univ, Dept Chem, Pittsburg, KS 66762 USA.
[Perez, J. Manuel] Univ Cent Florida, NanoSci Technol Ctr, Orlando, FL 32826 USA.
[Josephson, Lee] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Charlestown, MA 02129 USA.
RP Grimm, J (reprint author), Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Chem Program, 1275 York Ave, New York, NY 10065 USA.
EM grimmj@mskcc.org
RI Shaffer, Travis/I-6956-2015
FU Department of Defense Prostate Cancer Research Program of the
Congressionally Directed Medical Research Programs [W81XWH-12-1-0509];
Louis V. Gerstner Young Investigator Award; Starr Cancer Consortium
[I4-A427]; MSKCC Experimental Therapeutics Center; Alex's Lemonade Stand
Foundation; NIH [P30 CA008748-44 S5]; National Science Foundation [IGERT
0965983]
FX We thank Professor Lewis Cantley (Weill Cornell Medical College, Cornell
University), Professor Charles Sawyers (MSKCC) and Dr Horst Kessler
(Technische Universitat Munchen) for providing chemotherapeutics; Dr
Jason S. Lewis for providing animals; Dr Naga Vara Kishore Pillarsetty,
Dr Carl Le, Dr Simone Alidori, Dr Stefan Harmsen, Kuntalkumar Sevak, Dr
Priyanka Shukla and Florian Rechenmacher for expert technical
assistance. This study was supported by the Department of Defense
Prostate Cancer Research Program of the Congressionally Directed Medical
Research Programs under Award No. W81XWH-12-1-0509 to J.G. (opinions,
interpretations, conclusions and recommendations are those of the author
and are not necessarily endorsed by the funding agency), Louis V.
Gerstner Young Investigator Award (to J.G.), Starr Cancer Consortium
(I4-A427 to J.G.), the MSKCC Experimental Therapeutics Center (to J.G.),
Mr William H. and Mrs Alice Goodwin (to J.G.), the Alex's Lemonade Stand
Foundation (to C. K.) and the NIH (P30 CA008748-44 S5). T. M. S. is
funded by a National Science Foundation Integrative Graduate Education
and Research Traineeship (MAD, IGERT 0965983).
NR 43
TC 20
Z9 20
U1 7
U2 88
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD MAR
PY 2014
VL 5
AR 3384
DI 10.1038/ncomms4384
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE9BB
UT WOS:000334297600001
PM 24594970
ER
PT J
AU Lamoureux, F
Baud'huin, M
Calleja, LR
Jacques, C
Berreur, M
Redini, F
Lecanda, F
Bradner, JE
Heymann, D
Ory, B
AF Lamoureux, Francois
Baud'huin, Marc
Calleja, Lidia Rodriguez
Jacques, Camille
Berreur, Martine
Redini, Francoise
Lecanda, Fernando
Bradner, James E.
Heymann, Dominique
Ory, Benjamin
TI Selective inhibition of BET bromodomain epigenetic signalling interferes
with the bone-associated tumour vicious cycle
SO NATURE COMMUNICATIONS
LA English
DT Article
ID TRANSCRIPTION FACTOR RUNX2; OSTEOSARCOMA CELL-LINES; C-MYC;
SUPER-ENHANCERS; NUCLEAR-FACTOR; ONCOSTATIN-M; IN-VIVO; PROTEIN; CANCER;
EXPRESSION
AB The vicious cycle established between bone-associated tumours and bone resorption is the central problem with therapeutic strategies against primary bone tumours and bone metastasis. Here we report data to support inhibition of BET bromodomain proteins as a promising therapeutic strategy that target simultaneously the three partners of the vicious cycle. Treatment with JQ1, a BET bromodomain inhibitor, reduces cell viability of osteosarcoma cells and inhibits osteoblastic differentiation both in vitro and in vivo. These effects are associated with transcriptional silencing of MYC and RUNX2, resulting from the depletion of BRD4 from their respective loci. Moreover, JQ1 also inhibits osteoclast differentiation by interfering with BRD4-dependent RANKL activation of NFATC1 transcription. Collectively, our data indicate that JQ1 is a potent inhibitor of osteoblast and osteoclast differentiation as well as bone tumour development.
C1 [Lamoureux, Francois; Baud'huin, Marc; Calleja, Lidia Rodriguez; Jacques, Camille; Berreur, Martine; Redini, Francoise; Heymann, Dominique; Ory, Benjamin] INSERM, UMR 957, Equipe Labellise Ligue 2012, F-44035 Nantes, France.
[Lamoureux, Francois; Baud'huin, Marc; Calleja, Lidia Rodriguez; Jacques, Camille; Berreur, Martine; Redini, Francoise; Heymann, Dominique; Ory, Benjamin] Univ Nantes, Nantes Atlantique Univ, F-44035 Nantes, France.
[Baud'huin, Marc] Nantes Univ Hosp, F-44035 Nantes, France.
[Lecanda, Fernando] Univ Navarra, Ctr Appl Med Res CIMA, Div Oncol, Adhes & Metastasis Lab, Navarra 31008, Spain.
[Bradner, James E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Bradner, James E.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
RP Ory, B (reprint author), INSERM, UMR 957, Equipe Labellise Ligue 2012, 1 Rue Gaston Veil, F-44035 Nantes, France.
EM Benjamin.ory@univ-nantes.fr
RI Lamoureux, Francois/K-8021-2015; REDINI, Francoise/K-7981-2015; ory,
benjamin/K-8231-2015; Baud'huin, Marc/K-8519-2015
FU Seventh Framework Programme [264817-BONE-NET]; INSERM; Region Pays de la
loire; Fondation ARC
FX This paper was written as a part of research project that received
funding from the Seventh Framework Programme ([FP7/2007-2013]) under
Grant agreement number 264817-BONE-NET. C.J. is funded by INSERM and
Region Pays de la loire. F. La. is funded by INSERM and Fondation ARC.
We thank Douangsone Vadysirisack for critical review of the manuscript.
NR 44
TC 44
Z9 44
U1 4
U2 29
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD MAR
PY 2014
VL 5
AR 3511
DI 10.1038/ncomms4511
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AE9CQ
UT WOS:000334302200002
PM 24646477
ER
PT J
AU Estevez, AO
Morgan, KL
Szewczyk, NJ
Gems, D
Estevez, M
AF Estevez, Annette O.
Morgan, Kathleen L.
Szewczyk, Nathaniel J.
Gems, David
Estevez, Miguel
TI The neurodegenerative effects of selenium are inhibited by FOX() and
PINK1/PTEN regulation of insulin/insulin-like growth factor signaling in
Caenorhabditis elegans
SO NEUROTOXICOLOGY
LA English
DT Article
DE Selenium; Neurodegeneration; Insulin/insulin-like signaling; PTEN;
PINKI; Amyotrophic lateral sclerosis
ID AMYOTROPHIC-LATERAL-SCLEROSIS; COLORECTAL-CANCER CELLS; AGE-1 PI3
KINASE; SUPEROXIDE-DISMUTASE; C-ELEGANS; LIFE-SPAN; OXIDATIVE STRESS;
SODIUM SELENITE; TRANSCRIPTION FACTOR; INSULIN-RESISTANCE
AB Exposures to high levels of environmental selenium have been associated with motor neuron disease in both animals and humans and high levels of selenite have been identified in the cerebrospinal fluid of patients with amyotrophic lateral sclerosis (ALS). We have shown previously that exposures to high levels of sodium selenite in the environment of Caenorhabditis elegans adult animals can induce neurodegeneration and cell loss resulting in motor deficits and death and that this is at least partially caused by a reduction in cholinergic signaling across the neuromuscular junction. Here we provide evidence that reduction in insulin/insulin-like (IIS) signaling alters response to high dose levels of environmental selenium which in turn can regulate the IIS pathway. Most specifically we show that nuclear localization and thus activation of the OAF-16/forkhead box transcription factor occurs in response to selenium exposure although this was not observed in motor neurons of the ventral cord. Yet, tissue specific expression and generalized overexpression of DAF-16 can partially rescue the neurodegenerative and behavioral deficits observed with high dose selenium exposures in not only the cholinergic, but also the GABAergic motor neurons. In addition, two modifiers of IIS signaling, PTEN (phosphatase and tensin homolog, deleted on chromosome 10) and PINK1 (PTEN-induced putative kinase I) are required for the cellular antioxidant reduced glutathione to mitigate the selenium-induced movement deficits. Studies have suggested that environmental exposures can lead to ALS or other neurological diseases and this model of selenium-induced neurodegeneration developed in a genetically tractable organism provides a tool for examining the combined roles of genetics and environment in the neuro-pathologic disease process. (C) 2014 The Authors. Published by Elsevier Inc. All rights reserved.
C1 [Estevez, Annette O.; Estevez, Miguel] Univ Arizona, Coll Med, Dept Neurol, Tucson, AZ 85724 USA.
[Morgan, Kathleen L.; Estevez, Miguel] Vet Affairs Pittsburgh Healthcare Syst, Res & Dev, Pittsburgh, PA 15240 USA.
[Szewczyk, Nathaniel J.] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA.
[Gems, David] UCL, Inst Hlth Ageing, London WC1E 6BT, England.
[Gems, David] UCL, Dept Genet Evolut & Environm, London WC1E 6BT, England.
RP Estevez, AO (reprint author), Neurometrica, 1900 Millrace Dr,Suite 113N, Eugene, OR 97403 USA.
EM neurometrica@gmail.com; kathleen@immunetrics.com;
mbzns3@exmail.nottingham.ac.uk; david.gems@ucl.ac.uk;
m_estevez@yahoo.com
OI Estevez, Annette/0000-0001-8840-1340
FU Jim Himelic Foundation; Southern Arizona Foundation; Keatings Institute;
National Institutes of Environmental Health Sciences [R21-ES012305];
Career Development Award [ME] provided through the Office of Research
and Development, Department of Veterans Affairs; NIH National Center for
Research Resources (NCRR); International C. elegans Gene Knockout
Consortium
FX This research was supported by grants from the Jim Himelic Foundation
(ME), Southern Arizona Foundation (ME), Keatings Institute (ME),
National Institutes of Environmental Health Sciences [R21-ES012305 to AE
and ME], and a Career Development Award [ME] provided through the Office
of Research and Development, Department of Veterans Affairs. Some
nematode strains used in this work were provided by the Caenorhabditis
Genetics Center, which is funded by the NIH National Center for Research
Resources (NCRR) and the International C. elegans Gene Knockout
Consortium.
NR 114
TC 8
Z9 8
U1 3
U2 14
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0161-813X
EI 1872-9711
J9 NEUROTOXICOLOGY
JI Neurotoxicology
PD MAR
PY 2014
VL 41
BP 28
EP 43
DI 10.1016/j.neuro.2013.12.012
PG 16
WC Neurosciences; Pharmacology & Pharmacy; Toxicology
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology
GA AE6HW
UT WOS:000334092200004
PM 24406377
ER
PT J
AU Miodovnik, A
Edwards, A
Bellinger, DC
Hauser, R
AF Miodovnik, Amir
Edwards, Andrea
Bellinger, David C.
Hauser, Russ
TI Developmental neurotoxicity of ortho-phthalate diesters: Review of human
and experimental evidence
SO NEUROTOXICOLOGY
LA English
DT Review
DE Endocrine disruptors; Epidemiology; Neurodevelopment; Phthalates;
Prenatal
ID ENDOCRINE DISRUPTING CHEMICALS; ATTENTION-DEFICIT/HYPERACTIVITY
DISORDER; THYROID-HORMONE BINDING; SCHOOL-AGE-CHILDREN; LACTATIONAL
EXPOSURE; URINARY PHTHALATE; IN-UTERO; DI(2-ETHYLHEXYL) PHTHALATE;
PERINATAL EXPOSURE; DIBUTYL PHTHALATE
AB Ortho-phthalate diesters, or phthalates, are widely used synthetic chemicals found primarily in consumer products and polyvinyl chloride plastics. Experimental evidence suggests that several phthalates possess antiandrogenic properties and may disrupt endocrine pathways resulting in abnormal reproductive outcomes. Low-level exposure to phthalates has been well documented in humans, with higher levels found in children and women of childbearing age. Recent epidemiologic studies postulate that prenatal exposure to measurable urine phthalate concentrations may be associated with altered genital and pubertal development in infants and children. This review addresses the emerging evidence that some phthalates may have an adverse impact on the developing brain. The supporting animal studies and proposed mechanisms underlying the deleterious properties of phthalates in relation to neurodevelopmental outcomes are also discussed. While the observed associations are based on limited studies with a broad range of endpoints, the implications of such outcomes are of concern from a public health standpoint and merit further investigation given the widespread nature of the exposure. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Miodovnik, Amir; Bellinger, David C.] Boston Childrens Hosp, Boston, MA 02115 USA.
[Miodovnik, Amir; Bellinger, David C.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Edwards, Andrea] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Hauser, Russ] Massachusetts Gen Hosp, Boston, MA 02215 USA.
[Hauser, Russ] Harvard Univ, Sch Med, Boston, MA 02215 USA.
RP Miodovnik, A (reprint author), Boston Childrens Hosp, Dev Med Ctr, Boston, MA 02215 USA.
EM amir.miodovnik@childrens.harvard.edu
NR 81
TC 25
Z9 26
U1 7
U2 49
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0161-813X
EI 1872-9711
J9 NEUROTOXICOLOGY
JI Neurotoxicology
PD MAR
PY 2014
VL 41
BP 112
EP 122
DI 10.1016/j.neuro.2014.01.007
PG 11
WC Neurosciences; Pharmacology & Pharmacy; Toxicology
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology
GA AE6HW
UT WOS:000334092200012
PM 24486776
ER
PT J
AU Swirski, FK
Hilgendorf, I
Robbins, CS
AF Swirski, Filip K.
Hilgendorf, Ingo
Robbins, Clinton S.
TI From proliferation to proliferation: monocyte lineage comes full circle
SO SEMINARS IN IMMUNOPATHOLOGY
LA English
DT Review
DE Monocyte; Hematopoiesis; Macrophage; Proliferation; Atherosclerosis
ID HEMATOPOIETIC STEM-CELLS; LOW-DENSITY-LIPOPROTEIN; ATHEROSCLEROTIC
LESION DEVELOPMENT; MACROPHAGE-SPECIFIC EXPRESSION; TISSUE-RESIDENT
MACROPHAGES; ACUTE MYOCARDIAL-INFARCTION; MARROW PROGENITOR CELLS;
RECEPTOR KNOCKOUT MICE; A SCAVENGER RECEPTORS; BONE-MARROW
AB Monocytes are mononuclear circulating phagocytes that originate in the bone marrow and give rise to macrophages in peripheral tissue. For decades, our understanding of monocyte lineage was bound to a stepwise model that favored an inverse relationship between cellular proliferation and differentiation. Sophisticated molecular and surgical cell tracking tools have transformed our thinking about monocyte topo-ontogeny and function. Here, we discuss how recent studies focusing on progenitor proliferation and differentiation, monocyte mobilization and recruitment, and macrophage differentiation and proliferation are reshaping knowledge of monocyte lineage in steady state and disease.
C1 [Swirski, Filip K.; Hilgendorf, Ingo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA.
[Robbins, Clinton S.] Univ Toronto, Toronto Gen Res Inst, Heart & Stroke Richard Lewar Ctr Excellence Cardi, Toronto, ON M5G 1L7, Canada.
RP Swirski, FK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA.
EM fswirski@mgh.harvard.edu
FU NHLBI NIH HHS [R01 HL095612]
NR 152
TC 9
Z9 9
U1 2
U2 11
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1863-2297
EI 1863-2300
J9 SEMIN IMMUNOPATHOL
JI Semin. Immunopathol.
PD MAR
PY 2014
VL 36
IS 2
BP 137
EP 148
DI 10.1007/s00281-013-0409-1
PG 12
WC Immunology; Pathology
SC Immunology; Pathology
GA AF1UK
UT WOS:000334499200002
PM 24435095
ER
PT J
AU Nierenberg, A
AF Nierenberg, A.
TI Comparative effectiveness designs for bipolar disorder: signal or noise?
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 16th Annual Conference of the
International-Society-for-Bipolar-Disorders
CY MAR 18-21, 2014
CL Seoul, SOUTH KOREA
SP Int Soc Bipolar Disorders
C1 [Nierenberg, A.] 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 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD MAR
PY 2014
VL 16
SU 1
SI SI
BP 34
EP 34
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AC0FE
UT WOS:000332169400048
ER
PT J
AU Nierenberg, A
Hansen, N
Peters, A
Sylvia, LG
Magalhaes, PV
Berk, M
Otto, M
Miklowitz, D
Frank, E
Deckersbach, T
AF Nierenberg, A.
Hansen, N.
Peters, A.
Sylvia, L. G.
Magalhaes, P. V.
Berk, M.
Otto, M.
Miklowitz, D.
Frank, E.
Deckersbach, T.
TI Co-morbid anxiety moderates psychosocial treatment outcome for bipolar
depression
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 16th Annual Conference of the
International-Society-for-Bipolar-Disorders
CY MAR 18-21, 2014
CL Seoul, SOUTH KOREA
SP Int Soc Bipolar Disorders
C1 [Nierenberg, A.; Hansen, N.; Sylvia, L. G.; Deckersbach, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Peters, A.] Univ Illinois, Chicago, IL USA.
[Magalhaes, P. V.] Hosp Clin Porto Alegre, Natl Inst Translat Med, Porto Alegre, RS, Brazil.
[Berk, M.] Deakin Univ, Geelong, Vic 3217, Australia.
[Otto, M.] Boston Univ, Boston, MA 02215 USA.
[Miklowitz, D.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Frank, E.] Univ Pittsburgh, Pittsburgh, PA USA.
RI Magalhaes, Pedro/A-8519-2008
OI Magalhaes, Pedro/0000-0002-5644-6357
NR 0
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD MAR
PY 2014
VL 16
SU 1
SI SI
BP 43
EP 44
PG 2
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AC0FE
UT WOS:000332169400073
ER
PT J
AU Miklowitz, D
Stange, J
Sylvia, LG
Magalhaes, PV
Otto, M
Frank, E
Peters, A
Berkh, M
Nierenberg, A
Deckersbach, T
AF Miklowitz, D.
Stange, J.
Sylvia, L. G.
Magalhaes, P. V.
Otto, M.
Frank, E.
Peters, A.
Berkh, M.
Nierenberg, A.
Deckersbach, T.
TI Extreme attributions predict the course of bipolar disorder following
psychotherapy treatment for depression
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 16th Annual Conference of the
International-Society-for-Bipolar-Disorders
CY MAR 18-21, 2014
CL Seoul, SOUTH KOREA
SP Int Soc Bipolar Disorders
C1 [Miklowitz, D.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Stange, J.] Temple Univ, Philadelphia, PA 19122 USA.
[Sylvia, L. G.; Nierenberg, A.; Deckersbach, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Magalhaes, P. V.] Hosp Clin Porto Alegre, Natl Inst Translat Med, Porto Alegre, RS, Brazil.
[Otto, M.] Boston Univ, Boston, MA 02215 USA.
[Frank, E.] Univ Pittsburgh, Pittsburgh, PA USA.
[Peters, A.] Univ Illinois, Chicago, IL USA.
[Berkh, M.] Deakin Univ, Geelong, Vic 3217, Australia.
RI Magalhaes, Pedro/A-8519-2008
OI Magalhaes, Pedro/0000-0002-5644-6357
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD MAR
PY 2014
VL 16
SU 1
SI SI
BP 44
EP 44
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AC0FE
UT WOS:000332169400075
ER
PT J
AU Peters, A
Sylvia, LG
Magalhaes, PV
Miklowitz, D
Frank, E
Otto, M
Berk, M
Nierenberg, A
Deckersbach, T
AF Peters, A.
Sylvia, L. G.
Magalhaes, P. V.
Miklowitz, D.
Frank, E.
Otto, M.
Berk, M.
Nierenberg, A.
Deckersbach, T.
TI Age of onset, course of illness, and response to psychotherapy for
bipolar depression
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 16th Annual Conference of the
International-Society-for-Bipolar-Disorders
CY MAR 18-21, 2014
CL Seoul, SOUTH KOREA
SP Int Soc Bipolar Disorders
C1 [Peters, A.] Univ Illinois, Chicago, IL USA.
[Sylvia, L. G.; Nierenberg, A.; Deckersbach, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Magalhaes, P. V.] Hosp Clin Porto Alegre, Natl Inst Translat Med, Porto Alegre, RS, Brazil.
[Miklowitz, D.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Frank, E.] Univ Pittsburgh, Pittsburgh, PA USA.
[Otto, M.] Boston Univ, Boston, MA 02215 USA.
[Berk, M.] Deakin Univ, Geelong, Vic 3217, Australia.
RI Magalhaes, Pedro/A-8519-2008
OI Magalhaes, Pedro/0000-0002-5644-6357
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD MAR
PY 2014
VL 16
SU 1
SI SI
BP 44
EP 44
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AC0FE
UT WOS:000332169400074
ER
PT J
AU Yu, X
Ma, Y
Si, T
Jing, L
Liu, Z
Gang, W
Jing, S
Yiru, F
Yang, H
Zhang, Y
Wang, X
Gary, S
AF Yu, X.
Ma, Y.
Si, T.
Jing Li
Liu, Z.
Gang Wang
Jing Sun
Yiru Fang
Yang, H.
Zhang, Y.
Wang, X.
Gary, S.
TI Bipolarity index as an assessment instrument in the diagnosis and one
year outcome of bipolar disorders
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 16th Annual Conference of the
International-Society-for-Bipolar-Disorders
CY MAR 18-21, 2014
CL Seoul, SOUTH KOREA
SP Int Soc Bipolar Disorders
C1 [Yu, X.; Ma, Y.; Si, T.] Peking Univ, Inst Mental Hlth, Beijing 100871, Peoples R China.
[Jing Li] Sichuan Univ, Hua Xi Psychol Ctr, Chengdu 610064, Peoples R China.
[Liu, Z.] Xiang Ya 2nd Hosp, Changsha, Hunan, Peoples R China.
[Gang Wang] Beijing Anding Hosp, Beijing, Peoples R China.
[Jing Sun] Nanjing Brain Hosp, Nanjing, Jiangsu, Peoples R China.
[Yiru Fang] Shanghai Mental Hlth Ctr, Shanghai, Peoples R China.
[Yang, H.] Shenzhen Kangning Hosp, Shenzhen, Peoples R China.
[Zhang, Y.] Hangzhou 7th Hosp, Hangzhou, Zhejiang, Peoples R China.
[Wang, X.] Hebei Med Univ, Hosp 1, Shijiazhuang, Hebei, Peoples R China.
[Gary, S.] 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 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD MAR
PY 2014
VL 16
SU 1
SI SI
BP 48
EP 48
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AC0FE
UT WOS:000332169400086
ER
PT J
AU Baek, JH
Bernstein, EE
Nierenberg, AA
AF Baek, J. H.
Bernstein, E. E.
Nierenberg, A. A.
TI One carbon metabolism and bipolar disorder
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 16th Annual Conference of the
International-Society-for-Bipolar-Disorders
CY MAR 18-21, 2014
CL Seoul, SOUTH KOREA
SP Int Soc Bipolar Disorders
C1 [Baek, J. H.; Bernstein, E. E.; Nierenberg, A. A.] 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 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD MAR
PY 2014
VL 16
SU 1
SI SI
BP 51
EP 51
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AC0FE
UT WOS:000332169400096
ER
PT J
AU Peters, A
Sylvia, LG
Nierenberg, AA
Hansen, N
Stange, JP
Peckham, AD
Deckersbach, T
AF Peters, A.
Sylvia, L. G.
Nierenberg, A. A.
Hansen, N.
Stange, J. P.
Peckham, A. D.
Deckersbach, T.
TI Cognitive remediation and mindfulness- based cognitive therapy for
bipolar disorder
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 16th Annual Conference of the
International-Society-for-Bipolar-Disorders
CY MAR 18-21, 2014
CL Seoul, SOUTH KOREA
SP Int Soc Bipolar Disorders
C1 [Peters, A.] Univ Illinois, Chicago, IL USA.
[Sylvia, L. G.; Nierenberg, A. A.; Hansen, N.; Deckersbach, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Stange, J. P.] Temple Univ, Philadelphia, PA 19122 USA.
[Peckham, A. D.] Univ Calif Berkeley, Berkeley, CA 94720 USA.
NR 0
TC 0
Z9 0
U1 4
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD MAR
PY 2014
VL 16
SU 1
SI SI
BP 57
EP 57
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AC0FE
UT WOS:000332169400111
ER
PT J
AU Sellgren, C
Kegel, ME
Bergen, SE
Ekman, CJ
Olsson, S
Larsson, M
Sullivan, PF
Sklar, P
Purcell, S
Smoller, JW
Magnusson, PKE
Hultman, CM
Walther-Jallow, L
Svensson, CI
Lichtenstein, P
Engberg, G
Erhardt, S
Landen, M
AF Sellgren, C.
Kegel, M. E.
Bergen, S. E.
Ekman, C. J.
Olsson, S.
Larsson, M.
Sullivan, P. F.
Sklar, P.
Purcell, S.
Smoller, J. W.
Magnusson, P. K. E.
Hultman, C. M.
Walther-Jallow, L.
Svensson, C. I.
Lichtenstein, P.
Engberg, G.
Erhardt, S.
Landen, M.
TI An inflammatory pathway linked to psychosis in bipolar disorder
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 16th Annual Conference of the
International-Society-for-Bipolar-Disorders
CY MAR 18-21, 2014
CL Seoul, SOUTH KOREA
SP Int Soc Bipolar Disorders
C1 [Sellgren, C.; Bergen, S. E.; Magnusson, P. K. E.; Hultman, C. M.; Lichtenstein, P.; Landen, M.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Kegel, M. E.; Olsson, S.; Larsson, M.; Svensson, C. I.; Engberg, G.; Erhardt, S.] Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
[Ekman, C. J.] Karolinska Inst, Dept Clin Neurosci, Sect Psychiat, Stockholm, Sweden.
[Sullivan, P. F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Sullivan, P. F.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
[Sklar, P.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA.
[Purcell, S.; Smoller, J. W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Walther-Jallow, L.] Karolinska Inst, Dept Med, Ctr Infect Med, Stockholm, Sweden.
RI Magnusson, Patrik/C-4458-2017
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 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD MAR
PY 2014
VL 16
SU 1
SI SI
BP 65
EP 65
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AC0FE
UT WOS:000332169400128
ER
PT J
AU Ma, Y
Yu, X
Si, T
Li, J
Liu, Z
Wang, G
Sun, J
Fang, Y
Yang, H
Zhang, Y
Wang, X
Sachs, G
AF Ma, Y.
Yu, Xin
Si, T.
Li, Jing
Liu, Z.
Wang, Gang
Sun, Jing
Fang, Y.
Yang, H.
Zhang, Y.
Wang, X.
Sachs, G.
TI Bipolarity index as an assessment instrument in the diagnosis and one
year outcome of bipolar disorders
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 16th Annual Conference of the
International-Society-for-Bipolar-Disorders
CY MAR 18-21, 2014
CL Seoul, SOUTH KOREA
SP Int Soc Bipolar Disorders
C1 [Ma, Y.; Yu, Xin; Si, T.] Peking Univ, Inst Mental Hlth, Beijing 100871, Peoples R China.
[Li, Jing] Sichuan Univ, Huaxi Psychol Ctr, Chengdu 610064, Peoples R China.
[Liu, Z.] Xiang Ya 2nd Hosp, Changsha, Hunan, Peoples R China.
[Wang, Gang] Beijing Anding Hosp, Beijing, Peoples R China.
[Sun, Jing] Nanjing Brain Hosp, Nanjing, Jiangsu, Peoples R China.
[Fang, Y.] Shanghai Mental Hlth Ctr, Shanghai, Peoples R China.
[Yang, H.] Shenzhen Kangning Hosp, Shenzhen, Peoples R China.
[Zhang, Y.] Hangzhou 7th Hosp, Hangzhou, Zhejiang, Peoples R China.
[Wang, X.] Hebei Med Univ, Hosp 1, Shijiazhuang, Hebei, Peoples R China.
[Sachs, G.] 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 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD MAR
PY 2014
VL 16
SU 1
SI SI
BP 68
EP 68
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AC0FE
UT WOS:000332169400136
ER
PT J
AU Peters, A
West, A
Eisner, L
Deckersbach, T
AF Peters, A.
West, A.
Eisner, L.
Deckersbach, T.
TI The burden of recurrent mood episodes in bipolar I disorder: results
from the national epidemiological survey on alcohol and related
conditions (NESARC)
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 16th Annual Conference of the
International-Society-for-Bipolar-Disorders
CY MAR 18-21, 2014
CL Seoul, SOUTH KOREA
SP Int Soc Bipolar Disorders
C1 [Peters, A.; West, A.] Univ Illinois, Chicago, IL USA.
[Eisner, L.; Deckersbach, T.] 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 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD MAR
PY 2014
VL 16
SU 1
SI SI
BP 117
EP 118
PG 2
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AC0FE
UT WOS:000332169400286
ER
PT J
AU Loebel, A
Cucchiaro, J
Silva, R
Sarma, K
Kroger, H
Calabrese, J
Sachs, G
Grossman, F
Pikalov, A
AF Loebel, A.
Cucchiaro, J.
Silva, R.
Sarma, K.
Kroger, H.
Calabrese, J.
Sachs, G.
Grossman, F.
Pikalov, A.
TI Efficacy and safety of lurasidone in bipolar depression: results from
two, double blind, placebo-controlled studies
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 16th Annual Conference of the
International-Society-for-Bipolar-Disorders
CY MAR 18-21, 2014
CL Seoul, SOUTH KOREA
SP Int Soc Bipolar Disorders
C1 [Loebel, A.; Cucchiaro, J.; Silva, R.; Sarma, K.; Kroger, H.; Grossman, F.; Pikalov, A.] Sunov Pharmaceut Inc, Clin Dev, Ft Lee, NJ USA.
[Calabrese, J.] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA.
[Sachs, G.] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA.
[Sachs, G.] Massachusetts Gen Hosp, Res Program, 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 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD MAR
PY 2014
VL 16
SU 1
SI SI
BP 131
EP 132
PG 2
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AC0FE
UT WOS:000332169400332
ER
PT J
AU Ostergaard, SD
Straszek, S
Petrides, G
Skadhede, S
Jensen, SOW
Munk-Jorgensen, P
Nielsen, J
AF Ostergaard, Soren Dinesen
Straszek, Sune
Petrides, Georgios
Skadhede, Soren
Jensen, Signe Olrik Wallenstein
Munk-Jorgensen, Povl
Nielsen, Jimmi
TI Risk factors for conversion from unipolar psychotic depression to
bipolar disorder
SO BIPOLAR DISORDERS
LA English
DT Article
DE epidemiology; bipolar disorder; population register; psychotic mood
disorders
ID POPULATION-BASED COHORT; DELUSIONAL DEPRESSION; MAJOR DEPRESSION;
OLDER-ADULTS; DOUBLE-BLIND; NONPSYCHOTIC DEPRESSION; SCHOOL PERFORMANCE;
CONTROLLED-TRIAL; NATIONAL COHORT; I DISORDER
AB Objectives
Patients with unipolar psychotic depression (PD) are at high risk of developing bipolar disorder (BD). This conversion has important implications for the choice of treatment. This study, therefore, aimed to identify risk factors associated with diagnostic conversion from PD to BD.
Methods
We conducted a population-based, historical prospective cohort study by merging data from Danish registers. Patients assigned an ICD-10 diagnosis of PD between 1 January 1995 and 31 December 2007 were identified in the Danish Central Psychiatric Research Register and were followed until the development of BD, death, loss to follow-up, or 31 December 2007. Potential risk factors for conversion to BD, also defined through various Danish registers, were tested in multiple logistic regression analyses with risk expressed as adjusted odds ratios (AOR).
Results
We identified 8,588 patients with PD, of whom 609 (7.1%) developed BD during follow-up. The following characteristics were significantly associated with diagnostic conversion from PD to BD: early onset of PD [AOR=0.99 (per year of increasing age), p=0.044], recurrent depression [AOR=1.02 (per episode), p=0.036], living alone (AOR=1.29, p=0.007), receiving a disability pension (AOR=1.55, p<0.001), and the highest educational level being a technical education (AOR=1.55, p<0.001), short-cycle higher education (AOR=2.65, p<0.001), or medium-cycle higher education (AOR=1.75, p<0.001).
Conclusions
Diagnostic conversion to BD was prevalent among patients with PD. The following characteristics were significantly associated with this conversion: early onset of PD, recurrent depression, living alone, receiving a disability pension, and the highest educational level being a technical education, short-cycle higher education, or medium-cycle higher education.
C1 [Ostergaard, Soren Dinesen; Jensen, Signe Olrik Wallenstein] Aalborg Univ Hosp, Aalborg Psychiat Hosp, Psychiat Res Unit, DK-9000 Aalborg, Denmark.
[Ostergaard, Soren Dinesen] Aarhus Univ Hosp, Inst Clin Med, DK-8000 Aarhus, Denmark.
[Ostergaard, Soren Dinesen] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA.
[Straszek, Sune] Aarhus Univ Hosp, Dept Q, Risskov, Denmark.
[Petrides, Georgios] Northshore Long Isl Jewish Hlth Syst, Zucker Hillside Hosp, Glen Oaks, NY USA.
[Skadhede, Soren; Munk-Jorgensen, Povl] Aarhus Univ Hosp, Dept M, Risskov, Denmark.
[Nielsen, Jimmi] Aalborg Univ Hosp, Aalborg Psychiat Hosp, Ctr Schizophrenia, DK-9000 Aalborg, Denmark.
RP Ostergaard, SD (reprint author), Aalborg Univ Hosp, Aalborg Psychiat Hosp, Psychiat Res Unit, Molleparkvej 10, DK-9000 Aalborg, Denmark.
EM sdo@rn.dk
OI Ostergaard, Soren Dinesen/0000-0002-8032-6208
FU Janssen-Cilag; Bristol-Myers Squibb; AstraZeneca; National Institute of
Mental Health (NIMH); Novartis; Proteus; Corcept Pharmaceuticals;
Sunovion; Servier; Lundbeck; Pfizer; Chempaq; Hemocue
FX SDO received speaking fees, consultant honoraria, and travel support
from Janssen-Cilag until April 2011; and he received travel support, on
one occasion in 2010, from Bristol-Myers Squibb. S. Straszek has
received speaking fees from Bristol-Myers Squibb and AstraZeneca; and
has served as a consultant to Pfizer. GP has received research support
from the National Institute of Mental Health (NIMH), Novartis, Proteus,
Corcept Pharmaceuticals, and Sunovion. PM-J has received non-conditional
educational grants and/or minor honoraria from AstraZeneca,
Janssen-Cilag, Servier, and Bristol-Myers Squibb. JN has received
research grants from Lundbeck, Pfizer, and Chempaq for clinical trials;
and speaker fees from Bristol-Myers Squibb, AstraZeneca, Janssen-Cilag,
Lundbeck, and Hemocue. S. Skadhede and SOWJ have no conflicts of
interest to report.
NR 83
TC 14
Z9 14
U1 1
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD MAR
PY 2014
VL 16
IS 2
BP 180
EP 189
DI 10.1111/bdi.12152
PG 10
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AC0TR
UT WOS:000332208700011
PM 24215495
ER
PT J
AU Ostacher, MJ
Iosifescu, DV
Hay, A
Blumenthal, SR
Sklar, P
Perlis, RH
AF Ostacher, Michael J.
Iosifescu, Dan V.
Hay, Aleena
Blumenthal, Sarah R.
Sklar, Pamela
Perlis, Roy H.
TI Pilot investigation of isradipine in the treatment of bipolar depression
motivated by genome-wide association
SO BIPOLAR DISORDERS
LA English
DT Article
DE proof-of-concept; calcium channel antagonist; depression;
dihydropyridine; L-type calcium channel; genome-wide; isradipine;
bipolar disorder
ID PSYCHIATRIC-DISORDERS; RELIABILITY; VALIDITY; CACNA1C; SCALE
AB Objectives
Motivated by genetic association data implicating L-type calcium channels in bipolar disorder liability, we sought to estimate the tolerability, safety, and efficacy of isradipine in the adjunctive treatment of bipolar depression.
Methods
A total of 12 patients with bipolar I or II depression entered this pilot, proof-of-concept eight-week investigation and 10 returned for at least one post-baseline visit. They were initiated on isradipine at 2.5mg and titrated up to 10mg daily, with blinded assessments of depression using the Montgomery-angstrom sberg Depression Rating Scale (MADRS) as well as adverse effects.
Results
Among the 10 patients, three had bipolar II disorder; all but two reported current episode duration longer than six months. In all, four of 10 completed the study; no significant adverse events were observed, although one subject discontinued treatment per protocol because of possible hypomanic symptoms which had resolved prior to study visit. In a mixed-effects model, mean improvement in depression severity, assessed by MADRS, was 2.1 (standard error=0.36) points/week (p<0.001). Two of the 10 subjects remitted and four of the 10 subjects experienced 50% or greater symptomatic improvement with treatment.
Conclusions
Isradipine merits further investigation for the treatment of bipolar depression. This preliminary trial illustrates the potential utility of genetic investigation in identifying psychiatric treatment targets.
C1 [Ostacher, Michael J.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA.
[Iosifescu, Dan V.; Sklar, Pamela] Icahn Sch Med Mt Sinai, Dept Psychiat, Mood & Anxiety Disorders Program, New York, NY USA.
[Hay, Aleena] Yale Univ, Dept Psychol, New Haven, CT 06520 USA.
[Blumenthal, Sarah R.; Perlis, Roy H.] Massachusetts Gen Hosp, Ctr Expt Drugs & Diagnost, Dept Psychiat, Boston, MA 02114 USA.
RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Ctr Expt Drugs & Diagnost, Dept Psychiat, Simches Res Bldg,185 Cambridge St,6th Floor, Boston, MA 02114 USA.
EM rperlis@chgr.mgh.harvard.edu
OI Ostacher, Michael/0000-0003-0353-7535
FU Stanley Center for Psychiatric Research at the Broad Institute,
Cambridge, MA, USA
FX This study was supported by the Stanley Center for Psychiatric Research
at the Broad Institute, Cambridge, MA, USA.
NR 19
TC 12
Z9 12
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD MAR
PY 2014
VL 16
IS 2
BP 199
EP 203
DI 10.1111/bdi.12143
PG 5
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AC0TR
UT WOS:000332208700013
PM 24372835
ER
PT J
AU Cho, HJ
Herzka, T
Zheng, W
Qi, J
Wilkinson, JE
Bradner, JE
Robinson, BD
Castillo-Martin, M
Cordon-Cardo, C
Trotman, LC
AF Cho, Hyejin
Herzka, Tali
Zheng, Wu
Qi, Jun
Wilkinson, John E.
Bradner, James E.
Robinson, Brian D.
Castillo-Martin, Mireia
Cordon-Cardo, Carlos
Trotman, Lloyd C.
TI RapidCaP, a Novel GEM Model for Metastatic Prostate Cancer Analysis and
Therapy, Reveals Myc as a Driver of Pten-Mutant Metastasis
SO CANCER DISCOVERY
LA English
DT Article
ID ENGINEERED MOUSE MODELS; TUMOR SUPPRESSION; ACTIVATION; MUTATIONS;
CELLS; MICE; AKT; IDENTIFICATION; INACTIVATION; INHIBITION
AB Genetically engineered mouse (GEM) models are a pillar of functional cancer research. Here, we developed RapidCaP, a GEM modeling system that uses surgical injection for viral gene delivery to the prostate. We show that in Pten deficiency, loss of p53 suffices to trigger metastasis to distant sites at greater than 50% penetrance by four months, consistent with results from human prostate cancer genome analysis. Live bioluminescence tracking showed that endogenous primary and metastatic disease responds to castration before developing lethal castration resistance. To our surprise, the resulting lesions showed no activation of Akt but activation of the Myc oncogene. Using RapidCaP, we find that Myc drives local prostate metastasis and is critical for maintenance of metastasis, as shown by using the Brd4 inhibitor JQ1. Taken together, our data suggest that a "MYC-switch" away from AKT forms a critical and druggable event in PTEN-mutant prostate cancer metastasis and castration resistance.
SIGNIFICANCE: The RapidCaP system introduces fast and flexible genetics for functional analysis and therapy for endogenous metastatic prostate cancer. The approach introduces targeting of MYC as a critical strategy against PTEN-deficient lethal prostate cancer. (C) 2014 AACR.
C1 [Cho, Hyejin; Herzka, Tali; Zheng, Wu; Trotman, Lloyd C.] Cold Spring Harbor Lab, Ctr Canc, Cold Spring Harbor, NY 11724 USA.
[Robinson, Brian D.] Weill Cornell Med Coll, New York Presbyterian Hosp, Dept Pathol & Lab Med, New York, NY USA.
[Castillo-Martin, Mireia; Cordon-Cardo, Carlos] Mt Sinai Sch Med, New York, NY USA.
[Qi, Jun] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA.
[Wilkinson, John E.] Univ Michigan, Sch Med, Unit Lab Anim Med, Ann Arbor, MI USA.
RP Trotman, LC (reprint author), Cold Spring Harbor Lab, Ctr Canc, 1 Bungtown Rd, Cold Spring Harbor, NY 11724 USA.
EM trotman@cshl.edu
RI Castillo-Martin, Mireia/H-6152-2013
FU NIH [CA137050]; Department of the Army [W81XWH-09-1-0557]; STARR
foundation; Robertson Research Fund of CSHL; CSHL CTD2 Cancer Target
Discovery and Development Network [U01CA168409]
FX This work was supported by grants to L.C. Trotman from the NIH
(CA137050), the Department of the Army (W81XWH-09-1-0557), the STARR
foundation, the Robertson Research Fund of CSHL, and by support from the
CSHL CTD2 Cancer Target Discovery and Development Network
Grant (U01CA168409, to S. Powers, Principal Investigator).
NR 44
TC 21
Z9 22
U1 0
U2 14
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 MAR
PY 2014
VL 4
IS 3
BP 318
EP 333
DI 10.1158/2159-8290.CD-13-0346
PG 16
WC Oncology
SC Oncology
GA AE2YC
UT WOS:000333838600024
PM 24444712
ER
PT J
AU Pan, RQ
Hogdal, LJ
Benito, JM
Bucci, D
Han, L
Borthakur, G
Cortes, J
DeAngelo, DJ
Debose, L
Mu, H
Dohner, H
Gaidzik, VI
Galinsky, I
Golfman, LS
Haferlach, T
Harutyunyan, KG
Hu, JH
Leverson, JD
Marcucci, G
Muschen, M
Newman, R
Park, E
Ruvolo, PP
Ruvolo, V
Ryan, J
Schindela, S
Zweidler-McKay, P
Stone, RM
Kantarjian, H
Andreeff, M
Konopleva, M
Letai, AG
AF Pan, Rongqing
Hogdal, Leah J.
Benito, Juliana M.
Bucci, Donna
Han, Lina
Borthakur, Gautam
Cortes, Jorge
DeAngelo, Daniel J.
Debose, LaKeisha
Mu, Hong
Doehner, Hartmut
Gaidzik, Verena I.
Galinsky, Ilene
Golfman, Leonard S.
Haferlach, Torsten
Harutyunyan, Karine G.
Hu, Jianhua
Leverson, Joel D.
Marcucci, Guido
Mueschen, Markus
Newman, Rachel
Park, Eugene
Ruvolo, Peter P.
Ruvolo, Vivian
Ryan, Jeremy
Schindela, Sonja
Zweidler-McKay, Patrick
Stone, Richard M.
Kantarjian, Hagop
Andreeff, Michael
Konopleva, Marina
Letai, Anthony G.
TI Selective BCL-2 Inhibition by ABT-199 Causes On-Target Cell Death in
Acute Myeloid Leukemia
SO CANCER DISCOVERY
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ANTI-APOPTOTIC MCL-1; MITOCHONDRIAL
APOPTOSIS; STEM-CELLS; ABT-737; SENSITIVITY; BAX; MICROENVIRONMENT;
RESISTANCE; PLATELETS
AB B-cell leukemia/lymphoma 2 (BCL-2) prevents commitment to programmed cell death at the mitochondrion. It remains a challenge to identify those tumors that are best treated by inhibition of BCL-2. Here, we demonstrate that acute myeloid leukemia (AML) cell lines, primary patient samples, and murine primary xenografts are very sensitive to treatment with the selective BCL-2 antagonist ABT-199. In primary patient cells, the median IC50 was approximately 10 nmol/L, and cell death occurred within 2 hours. Our ex vivo sensitivity results compare favorably with those observed for chronic lymphocytic leukemia, a disease for which ABT-199 has demonstrated consistent activity in clinical trials. Moreover, mitochondrial studies using BH3 profiling demonstrate activity at the mitochondrion that correlates well with cytotoxicity, supporting an on-target mitochondrial mechanism of action. Our protein and BH3 profiling studies provide promising tools that can be tested as predictive biomarkers in any clinical trial of ABT-199 in AML.
SIGNIFICANCE: Although targeting BCL-2 has largely been investigated in lymphoid cancers, we present preclinical results of targeting BCL-2 in AML. These results support clinical testing of the small-molecule BCL-2 antagonist ABT-199 in AML, accompanied by testing of predictive biomarkers used in this study.
C1 [Pan, Rongqing; Benito, Juliana M.; Han, Lina; Borthakur, Gautam; Cortes, Jorge; Debose, LaKeisha; Mu, Hong; Harutyunyan, Karine G.; Ruvolo, Peter P.; Ruvolo, Vivian; Kantarjian, Hagop; Andreeff, Michael; Konopleva, Marina] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA.
[Golfman, Leonard S.; Zweidler-McKay, Patrick] Univ Texas MD Anderson Canc Ctr, Dept Pediat, Houston, TX 77030 USA.
[Hu, Jianhua; Newman, Rachel] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
[Hogdal, Leah J.; Letai, Anthony G.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Hogdal, Leah J.; DeAngelo, Daniel J.; Galinsky, Ilene; Ryan, Jeremy; Stone, Richard M.; Letai, Anthony G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Bucci, Donna; Marcucci, Guido] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.
[Leverson, Joel D.] AbbVie Inc, N Chicago, IL USA.
[Mueschen, Markus; Park, Eugene] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
[Doehner, Hartmut; Gaidzik, Verena I.] Univ Hosp Ulm, Dept Internal Med 3, Ulm, Germany.
[Haferlach, Torsten; Schindela, Sonja] MLL Munich Leukemia Lab, Munich, Germany.
RP Letai, AG (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA.
EM mkonople@mdanderson.org; Anthony_Letai@dfci.harvard.edu
RI Han, Lina/J-5119-2015;
OI Han, Lina/0000-0003-1538-1734; Zweidler-McKay,
Patrick/0000-0001-6621-523X; Pan, Rongqing/0000-0002-9494-412X
FU Leukemia and Lymphoma Society [6387-13, LS2012-36558, AML-P01 5 P01
CA055164-19]
FX This work was supported by funds from the Leukemia and Lymphoma Society
Translational Research Award 6387-13 (to A. Letai) and LS2012-36558 and
AML-P01 5 P01 CA055164-19 (to M. Konopleva and M. Andreeff).
NR 31
TC 87
Z9 87
U1 4
U2 32
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 MAR
PY 2014
VL 4
IS 3
BP 362
EP 375
DI 10.1158/2159-8290.CD-13-0609
PG 14
WC Oncology
SC Oncology
GA AE2YC
UT WOS:000333838600027
PM 24346116
ER
PT J
AU Giri, J
Yeh, RW
Kennedy, KF
Hawkins, BM
Weinberg, I
Weinberg, MD
Parikh, SA
Garasic, J
Jaff, MR
White, CJ
Rosenfield, K
AF Giri, Jay
Yeh, Robert W.
Kennedy, Kevin F.
Hawkins, Beau M.
Weinberg, Ido
Weinberg, Mitchell D.
Parikh, Sahil A.
Garasic, Joseph
Jaff, Michael R.
White, Christopher J.
Rosenfield, Kenneth
TI Unprotected Carotid Artery Stenting in Modern Practice
SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS
LA English
DT Article
ID CEREBRAL PROTECTION DEVICES; RANDOMIZED-TRIAL; ACUTE STROKE;
ANGIOPLASTY; OUTCOMES; PREDICTORS; REGISTRY; RISK
C1 [Giri, Jay] Hosp Univ Penn, Cardiovasc Med Div, Philadelphia, PA 19104 USA.
[Yeh, Robert W.; Hawkins, Beau M.; Weinberg, Ido; Weinberg, Mitchell D.; Garasic, Joseph; Jaff, Michael R.; Rosenfield, Kenneth] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
[Kennedy, Kevin F.] Univ Missouri, St Lukes Midamer Heart Inst, Kansas City, MO 64110 USA.
[Parikh, Sahil A.] Univ Hosp Harrington Heart & Vasc Inst, Cleveland, OH USA.
[Parikh, Sahil A.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA.
[White, Christopher J.] Ochsner Med Ctr, John Ochsner Heart & Vasc Inst, New Orleans, LA USA.
RP Giri, J (reprint author), Hosp Univ Penn, Cardiovasc Med Div, Gates Pavill,9th Floor,3400 Spruce St, Philadelphia, PA 19104 USA.
EM giri.jay@gmail.com
RI White, Christopher/J-6686-2012
OI White, Christopher/0000-0001-8618-7539
FU Abbott Vascular; Bard Peripheral Vascular; Medtronic/Invatec; Atrium;
Boston Scientific Corp; Complete Conference Management; Harvard Clinical
Research Institute; Contego; Micell; Becker Ventures; Becker Venture
Services; Bluegrass Vascular Therapies; Hansen Biomedical; Trivascular;
Vortex Medical; Medtronic; CR Bard
FX Dr. Yeh is an investigator at the Harvard Clinical Research Institute
and has served as a consultant for the Kaiser Permanente Division of
Research. Dr. White is an investigator for the Carotid Stenting Boston
Scientific Surveillance Program (CABANA) trial from Boston Scientific
Corp. Dr. Rosenfield reports receiving research grants from Abbott
Vascular, Bard Peripheral Vascular, Medtronic/Invatec, and Atrium;
receiving consulting/advisory board fees from Abbott Vascular, Boston
Scientific Corp, Complete Conference Management, Harvard Clinical
Research Institute, Contego, Micell, and Becker Ventures; having equity
in Lumen Biomedical, Medical Stimulation Corp, Angioguard (Cordis), and
Micell; and serving on the board of directors for VIVA Physicians
(501C3). Dr. Jaff reports that he is a noncompensated advisor to Abbott
Vascular, Cordis Corporation, Covidien Vascular, Medtronic Vascular;
received advisory board fees from Becker Venture Services, Bluegrass
Vascular Therapies, Hansen Biomedical, Trivascular, and Vortex Medical;
has equity interests in Access Closure, Embolitech, Hotspur, Icon
Interventional, I. C. Sciences, Janacare, Northwind Medical, PQ Bypass,
Primacea, Sadra Medical, Trireme, Vascular Therapies; and is a member of
the board of directors of VIVA Physicians, a 501(c) 3 education and
research not-for-profit organization. Dr. Parikh receives research
grants from Medtronic and CR Bard and is a consultant to Medtronic and
Boston Scientific. Dr. Giri, Dr. Hawkins, Mr. Kennedy, Dr. I. Weinberg,
and Dr. M. Weinberg have no relevant disclosures.
NR 22
TC 3
Z9 3
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1522-1946
EI 1522-726X
J9 CATHETER CARDIO INTE
JI Catheter. Cardiovasc. Interv.
PD MAR 1
PY 2014
VL 83
IS 4
BP 595
EP 602
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AA9WR
UT WOS:000331444200016
PM 23804411
ER
PT J
AU Weinberg, I
Keyes, MJ
Giri, J
Rogers, KR
Olin, JW
White, CJ
Jaff, MR
AF Weinberg, Ido
Keyes, Michelle J.
Giri, Jay
Rogers, Kevin R.
Olin, Jeffrey W.
White, Christopher J.
Jaff, Michael R.
TI Blood Pressure Response to Renal Artery Stenting in 901 Patients From
Five Prospective Multicenter FDA-Approved Trials
SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS
LA English
DT Article
ID ATHEROSCLEROTIC RENOVASCULAR DISEASE; FRACTIONAL FLOW RESERVE; 4-YEAR
FOLLOW-UP; HYPERTENSIVE PATIENTS; BALLOON ANGIOPLASTY; RANDOMIZED-TRIAL;
PERCUTANEOUS REVASCULARIZATION; MEDICAL THERAPY; CLINICAL-TRIALS;
STENOSIS
C1 [Weinberg, Ido; Keyes, Michelle J.; Jaff, Michael R.] Massachusetts Gen Hosp, Inst Heart Vasc & Stroke Care, Boston, MA 02114 USA.
[Giri, Jay] Univ Penn, Cardiovasc Med Div, Philadelphia, PA 19104 USA.
[Rogers, Kevin R.] Univ Colorado, Div Cardiol, Denver, CO 80202 USA.
[Olin, Jeffrey W.] Icahn Sch Med, Zena & Michael A Wiener Cardiovasc Inst, New York, NY USA.
[Olin, Jeffrey W.] Icahn Sch Med, Marie Josee & Henry R Kravis Ctr Cardiovasc Hlth, New York, NY USA.
[White, Christopher J.] Univ Queensland, Ochsner Clin Sch, John Ochsner Heart & Vasc Inst, New Orleans, LA USA.
[White, Christopher J.] Ochsner Hlth Syst, New Orleans, LA USA.
RP Jaff, MR (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Warren 905, Boston, MA 02114 USA.
EM mjaff@partners.org
RI White, Christopher/J-6686-2012
OI White, Christopher/0000-0001-8618-7539
FU Neovasc, Vancouver, BC, Canada; St. Jude Medical, Saint Paul, MN
FX Conflict of interest: Michael R. Jaff: Board member, VIVA Physicians, a
501 c 3 not-for-profit education and research organization. Christopher
J. White: Research grant recipient with Neovasc, Vancouver, BC, Canada
and St. Jude Medical, Saint Paul, MN.
NR 35
TC 13
Z9 13
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1522-1946
EI 1522-726X
J9 CATHETER CARDIO INTE
JI Catheter. Cardiovasc. Interv.
PD MAR 1
PY 2014
VL 83
IS 4
BP 603
EP 609
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AA9WR
UT WOS:000331444200017
PM 24307609
ER
PT J
AU del Conde, I
Galin, ID
Trost, B
Kang, J
Lookstein, R
Woodward, M
Gustavson, S
Cambria, RP
Jaff, MR
Olin, JW
AF del Conde, Ian
Galin, Ira D.
Trost, Biana
Kang, Jeanwan
Lookstein, Robert
Woodward, Mark
Gustavson, Susan
Cambria, Richard P.
Jaff, Michael R.
Olin, Jeffrey W.
TI Renal Artery Duplex Ultrasound Criteria for the Detection of Significant
In-Stent Restenosis
SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS
LA English
DT Article
ID MULTIDETECTOR CT ANGIOGRAPHY; FOLLOW-UP; VELOCITY CRITERIA;
CAROTID-ARTERY; DOPPLER ULTRASOUND; STENOSIS; ULTRASONOGRAPHY;
DIAGNOSIS; DISEASE; INTERVENTIONS
C1 [del Conde, Ian; Galin, Ira D.; Trost, Biana; Gustavson, Susan; Olin, Jeffrey W.] Icahn Sch Med Mt Sinai, Zena & Michael A Wiener Cardiovasc Inst, New York, NY USA.
[del Conde, Ian; Galin, Ira D.; Trost, Biana; Gustavson, Susan; Olin, Jeffrey W.] Icahn Sch Med Mt Sinai, Marie Josee & Henry R Kravis Ctr Cardiovasc Hlth, New York, NY USA.
[Kang, Jeanwan; Cambria, Richard P.; Jaff, Michael R.] Massachusetts Gen Hosp, Vasc Ctr, Boston, MA 02114 USA.
[Lookstein, Robert] Icahn Sch Med Mt Sinai, Dept Radiol, Div Vasc & Intervent Radiol, New York, NY USA.
[Woodward, Mark] Univ Sydney, George Inst Global Hlth, Sydney, NSW 2006, Australia.
RP Olin, JW (reprint author), Mt Sinai Sch Med, Zena & Michael A Wiener Cardiovasc Inst, One Gustave L Levy Pl,Box 1033, New York, NY 10029 USA.
EM jeffrey.olin@mountsinai.org
RI Woodward, Mark/D-8492-2015
NR 37
TC 4
Z9 4
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1522-1946
EI 1522-726X
J9 CATHETER CARDIO INTE
JI Catheter. Cardiovasc. Interv.
PD MAR 1
PY 2014
VL 83
IS 4
BP 612
EP 618
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AA9WR
UT WOS:000331444200019
PM 24155154
ER
PT J
AU Filbin, MR
Arias, SA
Camargo, CA
Barche, A
Pallin, DJ
AF Filbin, Michael R.
Arias, Sarah A.
Camargo, Carlos A., Jr.
Barche, Apurv
Pallin, Daniel J.
TI Sepsis Visits and Antibiotic Utilization in U.S. Emergency Departments
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE antibacterial agents; emergency treatment; epidemiology; mortality;
sepsis
ID RESISTANT STAPHYLOCOCCUS-AUREUS; GOAL-DIRECTED THERAPY; UNITED-STATES;
SEPTIC SHOCK; ANTIMICROBIAL THERAPY; EPIDEMIOLOGY; POPULATION;
INFECTIONS; MORTALITY; SURVIVAL
AB Objectives: To monitor the frequency of sepsis visits in U.S. emergency departments and assess the appropriateness of antibiotic utilization.
Design: We analyzed data from the National Hospital Ambulatory Medical Care Survey, defining sepsis as an explicit diagnosis of sepsis via International Classification of Diseases, 9th Revision, Clinical Modification codes 038, 995.91, 995.92, or 785.52. We also monitored trends using cases inferred by infection plus organ dysfunction without explicit diagnosis of sepsis, which we refer to as implicit sepsis cases. We assess changes in visit frequency and ascertain emergency department antibiotic administration rates.
Setting: Four-stage probability sample of visits to U.S. emergency departments, excluding Federal/military.
Patients: Adult emergency department visits, United States, 1994-2009.
Measurements and Main Results: Sepsis was diagnosed explicitly at 260,000 visits per year in U.S. emergency departments (95% CI, 251,000-270,000) or 1.23 visits per 1,000 U.S. population. The visit rate remained stable from 1994 to 2009 (p for trend 0.42). By contrast, the rate of visits with an implicit diagnosis of sepsis increased by 0.07 every 2 years (95% CI, 0.04-0.10; p for trend 0.002). Antibiotics were prescribed in the emergency department during 61% (95% CI, 57-65) of explicit sepsis visits. This increased from 52% in 1994-1997 to 69% in 2006-2009 (difference, 17%; 95% CI, 16.8-17.2). Of antibiotic regimens, 18% covered methicillin-resistant Staphylococcus aureus, 27% Pseudomonas, and 10% extended-spectrum beta-lactamase-producing bacteria, without evidence of targeting according to known risk factors. Of explicit sepsis cases, 31% were admitted to the ICU with 40% mortality (95% CI, 30-51). Overall hospital mortality was 17% (95% CI, 11-22).
Conclusions: Explicitly diagnosed sepsis visits did not become more common during 1994-2009. Our data suggest that many emergency department patients with sepsis do not receive antibiotics until they arrive on the inpatient unit. When antibiotics are used among septic emergency department patients, drug-resistant bacteria are covered infrequently. These methods provide a simple approach to tracking the frequency with which sepsis is diagnosed among emergency department patients and to monitoring antibiotic therapy.
C1 [Filbin, Michael R.; Arias, Sarah A.; Camargo, Carlos A., Jr.; Barche, Apurv] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Pallin, Daniel J.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA.
[Pallin, Daniel J.] Cambridge Hlth Alliance, Dept Emergency Med, Cambridge, MA USA.
RP Filbin, MR (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
EM mfilbin@partners.org
RI Pallin, Daniel/H-6382-2013;
OI Pallin, Daniel/0000-0002-8517-9702; Arias, Sarah/0000-0003-1832-8824
FU Department of Emergency Medicine at Massachusetts General Hospital
FX Dr. Filbin is employed by the Massachusetts General Hospital, provided
expert testimony for Padberg & Corrigan Law Firm, and receives royalties
from Wolters Kluwer/Lippincott Williams & Wilkins. Dr. Arias'
institution received support for review activities from Emergency
Medicine Network (EMNet-a seed grant from the Department of Emergency
Medicine at Massachusetts General Hospital was used to pay for Dr.
Arias' time on this project). The remaining authors have disclosed that
they do not have any potential conflicts of interest.
NR 27
TC 16
Z9 16
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0090-3493
EI 1530-0293
J9 CRIT CARE MED
JI Crit. Care Med.
PD MAR
PY 2014
VL 42
IS 3
BP 528
EP 535
DI 10.1097/CCM.0000000000000037
PG 8
WC Critical Care Medicine
SC General & Internal Medicine
GA AA9AX
UT WOS:000331387200033
PM 24201179
ER
PT J
AU Shaikh, H
Laghi, F
AF Shaikh, Hameeda
Laghi, Franco
TI Eating on Noninvasive Ventilation
SO CRITICAL CARE MEDICINE
LA English
DT Editorial Material
DE chronic obstructive pulmonary disease; noninvasive ventilation;
nutrition; respiratory failure; swallowing
ID OBSTRUCTIVE PULMONARY-DISEASE; COORDINATION; VOLUME; RESPIRATION; TUBE
C1 [Shaikh, Hameeda] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Pulm & Crit Care Sect, Hines, IL 60141 USA.
[Laghi, Franco] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA.
[Laghi, Franco] Loyola Univ, Div Pulm & Crit Care, Dept Med, Maywood, IL 60153 USA.
RP Shaikh, H (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Pulm & Crit Care Sect, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA.
NR 15
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
EI 1530-0293
J9 CRIT CARE MED
JI Crit. Care Med.
PD MAR
PY 2014
VL 42
IS 3
BP 737
EP 738
DI 10.1097/CCM.0000000000000002
PG 2
WC Critical Care Medicine
SC General & Internal Medicine
GA AA9AX
UT WOS:000331387200062
PM 24534964
ER
PT J
AU Saddawi-Konefka, D
Berg, SM
Nejad, SH
Bittner, EA
AF Saddawi-Konefka, Daniel
Berg, Sheri M.
Nejad, Shamim H.
Bittner, Edward A.
TI Catatonia in the ICU: An Important and Underdiagnosed Cause of Altered
Mental Status. A Case Series and Review of the Literature
SO CRITICAL CARE MEDICINE
LA English
DT Letter
DE antipsychotic agents; benzodiazepines; catatonia; critical care;
delirium; dopamine antagonists; encephalopathy; neuroleptic malignant
syndrome; psychiatry
ID NEUROLEPTIC MALIGNANT SYNDROME; BENZODIAZEPINE WITHDRAWAL;
ELECTROCONVULSIVE-THERAPY; LETHAL CATATONIA; RISK-FACTOR; ECT; LORAZEPAM
AB Objective: Catatonia is a neuropsychiatric syndrome with motor and behavioral symptoms occurring in patients with or without a history of psychiatric illness. Although it is associated with significant morbidity and mortality, the prevalence of catatonia in the ICU setting is unknown. The diagnosis and management of catatonia in the critically ill patient raises unique challenges. Furthermore, the diagnosis and management are not included in most critical care curricula. The objective of this retrospective study is to increase the awareness of this clinically important condition among critical care providers.
Design: Retrospective case series study.
Setting: Multiple critical care units at a university-affiliated tertiary care hospital.
Patients: Five critically ill patients with catatonia, aged 17 to 78.
Interventions: None.
Measurements and Main Results: All notes, laboratory data, imaging results, other diagnostic studies, therapeutic interventions, and responses to treatment were reviewed for five critically ill patients with catatonia. No unifying cause of catatonia or predisposing conditions were identified for these patients. Currently available diagnostic criteria for catatonia were found to be nonspecific in the ICU setting. New diagnostic criteria for catatonia specific to the critically ill patient are proposed.
Conclusions: Catatonia can occur in a wide variety of critical care settings, with or without precedent psychiatric illness, and it may be exacerbated or induced by common intensive care practices. Psychomotor findings are imperative in examination of critically ill patients with altered mental status in order to diagnose catatonia.
C1 [Saddawi-Konefka, Daniel; Berg, Sheri M.; Bittner, Edward A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Nejad, Shamim H.] Massachusetts Gen Hosp, Div Psychiat & Med, Dept Psychiat, Psychiat Consultat Serv, Boston, MA 02114 USA.
RP Saddawi-Konefka, D (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,WHT 437, Boston, MA 02114 USA.
EM dsaddawi@gmail.com
NR 33
TC 10
Z9 10
U1 0
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
EI 1530-0293
J9 CRIT CARE MED
JI Crit. Care Med.
PD MAR
PY 2014
VL 42
IS 3
BP E234
EP E241
DI 10.1097/CCM.0000000000000053
PG 8
WC Critical Care Medicine
SC General & Internal Medicine
GA AA9AX
UT WOS:000331387200007
PM 24275514
ER
PT J
AU Zulauf, CA
Sprich, SE
Safren, SA
Wilens, TE
AF Zulauf, Courtney A.
Sprich, Susan E.
Safren, Steven A.
Wilens, Timothy E.
TI The Complicated Relationship Between Attention Deficit/Hyperactivity
Disorder and Substance Use Disorders
SO CURRENT PSYCHIATRY REPORTS
LA English
DT Article
DE Adolescence; Substance use disorders; Attention deficit/hyperactivity
disorder; Stimulants comorbidity; Cognitive-behavioral therapy
ID DEFICIT-HYPERACTIVITY DISORDER; RANDOMIZED CONTROLLED-TRIAL;
COGNITIVE-BEHAVIORAL THERAPY; MEDICATION-TREATED ADULTS;
PLACEBO-CONTROLLED TRIAL; OSMOTIC-RELEASE METHYLPHENIDATE; ALCOHOL-USE
DISORDERS; SUPPLEMENT NCS-A; FOLLOW-UP; DRUG-USE
AB Adolescents and young adults with substance use disorders (SUD) and attention deficit/hyperactivity disorder (ADHD) are increasingly presenting in clinical practice. The overlap and role of treatment for these co-occurring disorders remains unclear. A review of the literature was conducted to highlight and update recent evidence on the overlap of ADHD and SUD, the role of ADHD medication on later SUD, and the treatment of ADHD and SUD in adolescents and young adults. Recent work continues to highlight the high risk for comorbid ADHD in patients with SUD; and conversely, the high risk for SUD developing in ADHD across the lifespan, particularly in the context of comorbid conduct disorder. Although the data remains discordant, it appears that ADHD pharmacotherapy does not increase the risk for SUD. Medication treatment alone does not appear to be particularly effective in treating SUD in currently active substance abusing individuals with ADHD. Structured therapies may be effective in treating adolescents and young adults with ADHD and SUD. Further controlled trials evaluating the sequence and effect of structured psychotherapies and/or ADHD pharmacotherapy on SUD relapse in these groups are warranted.
C1 [Zulauf, Courtney A.; Wilens, Timothy E.] Massachusetts Gen Hosp, Clin Program Pediat Psychopharmacol & Adult ADHD, Boston, MA 02114 USA.
[Zulauf, Courtney A.; Wilens, Timothy E.] Massachusetts Gen Hosp, Res Program Pediat Psychopharmacol & Adult ADHD, Boston, MA 02114 USA.
[Sprich, Susan E.] Massachusetts Gen Hosp, Cognit Behav Therapy Program, Boston, MA 02114 USA.
[Safren, Steven A.] Massachusetts Gen Hosp, Dept Behav Med, Boston, MA 02114 USA.
[Wilens, Timothy E.] Massachusetts Gen Hosp, Ctr Addict Med, Boston, MA 02114 USA.
[Wilens, Timothy E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Wilens, TE (reprint author), Massachusetts Gen Hosp, YAW 6A,55 Fruit St, Boston, MA 02114 USA.
EM twilens@partners.org
FU NIH(NIDA); Shire
FX Dr. Timothy Wilens receives or has received grant support from the
following sources: NIH(NIDA) and Shire. Dr. Wilens is or has been a
consultant for: Euthymics, NIH (NIDA), Shire, Tris and Theravance. Dr.
Wilens has a published book with Guilford Press. Straight Talk About
Psychiatric Medications for Kids. Dr. Wilens is a consultant to the US
National Football League (ERM Associates), U.S. Minor/Major League
Baseball and Bay Cove Human Services (Clinical Services).
NR 92
TC 13
Z9 13
U1 2
U2 18
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1523-3812
EI 1535-1645
J9 CURR PSYCHIAT REP
JI Curr. Psychiatry Rep.
PD MAR
PY 2014
VL 16
IS 3
AR 436
DI 10.1007/s11920-013-0436-6
PG 11
WC Psychiatry
SC Psychiatry
GA AE5VP
UT WOS:000334057700003
PM 24526271
ER
PT J
AU Guenova, E
Watanabe, R
Gehad, A
Teague, JE
Adams, N
Dorosario, AA
Glinert, R
Walsch, D
Tawa, M
Carter, JB
Chaney, KA
Fisher, DE
Cutler, CS
Kupper, TS
Clark, RA
AF Guenova, E.
Watanabe, R.
Gehad, A.
Teague, J. E.
Adams, N.
Dorosario, A. A.
Glinert, R.
Walsch, D.
Tawa, M.
Carter, J. B.
Chaney, K. A.
Fisher, D. E.
Cutler, C. S.
Kupper, T. S.
Clark, R. A.
TI Reversible suppression of normal thymic output in patients with leukemic
cutaneous T cell lymphoma
SO EXPERIMENTAL DERMATOLOGY
LA English
DT Meeting Abstract
CT 41st Annual Meeting of the Arbeitsgemeinschaft-Dermatologische-Forschung
(ADF)
CY MAR 13-15, 2014
CL Cologne, GERMANY
SP Arbeitsgemeinschaft Dermatologische Forsch
C1 Harvard Univ, Skin Dis Res Ctr, Boston, MA 02446 USA.
Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02446 USA.
RI Guenova, Emmanuella/A-4656-2015
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 0906-6705
EI 1600-0625
J9 EXP DERMATOL
JI Exp. Dermatol.
PD MAR
PY 2014
VL 23
IS 3
BP E35
EP E35
PG 1
WC Dermatology
SC Dermatology
GA AC2MP
UT WOS:000332335500228
ER
PT J
AU Tosto, MG
Petrill, SA
Halberda, J
Trzaskowski, M
Tikhomirova, TN
Bogdanova, OY
Ly, R
Wilmer, JB
Naiman, DQ
Germine, L
Plomin, R
Kovas, Y
AF Tosto, M. G.
Petrill, S. A.
Halberda, J.
Trzaskowski, M.
Tikhomirova, T. N.
Bogdanova, O. Y.
Ly, R.
Wilmer, J. B.
Naiman, D. Q.
Germine, L.
Plomin, R.
Kovas, Y.
TI Why do we differ in number sense? Evidence from a genetically sensitive
investigation
SO INTELLIGENCE
LA English
DT Article
DE Number sense; Mathematical ability; Behaviour genetics; Heritability
Directional selection
ID MATHEMATICAL LEARNING-DISABILITY; EARLY LITERACY DEVELOPMENT;
GENOME-WIDE ASSOCIATION; COMMON SNPS EXPLAIN; INDIVIDUAL-DIFFERENCES;
ENVIRONMENTAL ETIOLOGY; NUMERICAL CAPACITIES; CONTINUOUS QUANTITY;
GENDER-DIFFERENCES; LONGITUDINAL TWIN
AB Basic intellectual abilities of quantity and numerosity estimation have been detected across animal species. Such abilities are referred to as 'number sense'. For human species, individual differences in number sense are detectable early in life, persist in later development, and relate to general intelligence. The origins of these individual differences are unknown. To address this question, we conducted the first large-scale genetically sensitive investigation of number sense, assessing numerosity discrimination abilities in 837 pairs of monozygotic and 1422 pairs of dizygotic 16-year-old twin pairs. Univariate genetic analysis of the twin data revealed that number sense is modestly heritable (32%), with individual differences being largely explained by non-shared environmental influences (68%) and no contribution from shared environmental factors. Sex-Limitation model fitting revealed no differences between males and females in the etiology of individual differences in number sense abilities. We also carried out Genome-wide Complex Trait Analysis (GCTA) that estimates the population variance explained by additive effects of DNA differences among unrelated individuals. For 1118 unrelated individuals in our sample with genotyping information on 1.7 million DNA markers, GCTA estimated zero heritability for number sense, unlike other cognitive abilities in the same twin study where the GCTA heritability estimates were about 25%. The low heritability of number sense, observed in this study, is consistent with the directional selection explanation whereby additive genetic variance for evolutionary important traits is reduced. (C) 2014 The Authors. Published by Elsevier Inc. All rights reserved.
C1 [Tosto, M. G.] Univ York, Dept Psychol, York YO10 5DD, N Yorkshire, England.
[Tosto, M. G.; Tikhomirova, T. N.; Bogdanova, O. Y.; Kovas, Y.] Tomsk State Univ, Dept Psychol, Tomsk 634050, Russia.
[Petrill, S. A.] Ohio State Univ, Columbus, OH 43210 USA.
[Halberda, J.; Ly, R.; Naiman, D. Q.] Johns Hopkins Univ, Dept Psychol & Brain Sci, Baltimore, MD 21218 USA.
[Trzaskowski, M.; Plomin, R.; Kovas, Y.] Kings Coll London, MRC Social Genet & Dev Psychiat Ctr, Inst Psychiat, London SE5 8AF, England.
[Wilmer, J. B.] Wellesley Coll, Dept Psychol, Wellesley, MA 02481 USA.
[Germine, L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA.
[Kovas, Y.] Univ London, London SE14 6NW, England.
RP Tosto, MG (reprint author), Univ York, Dept Psychol, York YO10 5DD, N Yorkshire, England.
EM maria.tosto@york.ac.uk
RI Bogdanova, Olga/N-3018-2014; Tikhomirova, Tatiana/N-3016-2014;
OI Ly, Ryan/0000-0001-9238-0642; Plomin, Robert/0000-0002-0756-3629;
Germine, Laura/0000-0001-8690-8412; Trzaskowski,
Maciej/0000-0001-8559-6525
FU European Research Council [295366]; Medical Research Council [G0500079,
G0500079(73692), G0901245, G9817803B]; NICHD NIH HHS [R01 HD044454, R01
HD046167, R01 HD059215, R01 HD068728]
NR 87
TC 4
Z9 5
U1 4
U2 26
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0160-2896
EI 1873-7935
J9 INTELLIGENCE
JI Intelligence
PD MAR-APR
PY 2014
VL 43
BP 35
EP 46
DI 10.1016/j.intell.2013.12.007
PG 12
WC Psychology, Multidisciplinary
SC Psychology
GA AE5DG
UT WOS:000334007400005
PM 24696527
ER
PT J
AU Mueller, EL
Park, ER
Davis, MM
AF Mueller, Emily L.
Park, Elyse R.
Davis, Matthew M.
TI What the Affordable Care Act Means for Survivors of Pediatric Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID HEALTH-INSURANCE COVERAGE; CHILDHOOD-CANCER; ADULT SURVIVORS
C1 [Mueller, Emily L.; Davis, Matthew M.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Park, Elyse R.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA.
[Davis, Matthew M.] Inst Healthcare Policy & Innovat, Ann Arbor, MI USA.
RP Mueller, EL (reprint author), Univ Michigan, Ann Arbor, MI 48109 USA.
FU NICHD NIH HHS [T32 HD007534, T32 HD07534]
NR 14
TC 9
Z9 9
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2014
VL 32
IS 7
BP 615
EP +
DI 10.1200/JCO.2013.52.6467
PG 4
WC Oncology
SC Oncology
GA AC4HY
UT WOS:000332483100005
PM 24395862
ER
PT J
AU Schwartz, MD
Valdimarsdottir, HB
Peshkin, BN
Mandelblatt, J
Nusbaum, R
Huang, AT
Chang, YJ
Graves, K
Isaacs, C
Wood, M
McKinnon, W
Garber, J
McCormick, S
Kinney, AY
Luta, G
Kelleher, S
Leventhal, KG
Vegella, P
Tong, A
King, L
AF Schwartz, Marc D.
Valdimarsdottir, Heiddis B.
Peshkin, Beth N.
Mandelblatt, Jeanne
Nusbaum, Rachel
Huang, An-Tsun
Chang, Yaojen
Graves, Kristi
Isaacs, Claudine
Wood, Marie
McKinnon, Wendy
Garber, Judy
McCormick, Shelley
Kinney, Anita Y.
Luta, George
Kelleher, Sarah
Leventhal, Kara-Grace
Vegella, Patti
Tong, Angie
King, Lesley
TI Randomized Noninferiority Trial of Telephone Versus In-Person Genetic
Counseling for Hereditary Breast and Ovarian Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID POLICY STATEMENT UPDATE; COST-EFFECTIVENESS; MUTATION CARRIERS;
AMERICAN-SOCIETY; RISK; SUSCEPTIBILITY; COMMUNICATION; BRCA1; WOMEN;
VALIDATION
AB Purpose Although guidelines recommend in-person counseling before BRCA1/BRCA2 gene testing, genetic counseling is increasingly offered by telephone. As genomic testing becomes more common, evaluating alternative delivery approaches becomes increasingly salient. We tested whether telephone delivery of BRCA1/2 genetic counseling was noninferior to in-person delivery.
Patients and Methods Participants (women age 21 to 85 years who did not have newly diagnosed or metastatic cancer and lived within a study site catchment area) were randomly assigned to usual care (UC; n = 334) or telephone counseling (TC; n = 335). UC participants received in-person pre- and post-test counseling; TC participants completed all counseling by telephone. Primary outcomes were knowledge, satisfaction, decision conflict, distress, and quality of life; secondary outcomes were equivalence of BRCA1/2 test uptake and costs of delivering TC versus UC.
Results TC was noninferior to UC on all primary outcomes. At 2 weeks after pretest counseling, knowledge (d = 0.03; lower bound of 97.5% CI, -0.61), perceived stress (d = -0.12; upper bound of 97.5% CI, 0.21), and satisfaction (d = -0.16; lower bound of 97.5% CI, -0.70) had group differences and confidence intervals that did not cross their 1-point noninferiority limits. Decision conflict (d = 1.1; upper bound of 97.5% CI, 3.3) and cancer distress (d = -1.6; upper bound of 97.5% CI, 0.27) did not cross their 4-point noninferiority limit. Results were comparable at 3 months. TC was not equivalent to UC on BRCA1/2 test uptake (UC, 90.1%; TC, 84.2%). TC yielded cost savings of $114 per patient.
Conclusion Genetic counseling can be effectively and efficiently delivered via telephone to increase access and decrease costs.
C1 [Schwartz, Marc D.; Peshkin, Beth N.; Mandelblatt, Jeanne; Nusbaum, Rachel; Huang, An-Tsun; Chang, Yaojen; Graves, Kristi; Isaacs, Claudine; Luta, George; Kelleher, Sarah; Leventhal, Kara-Grace; Vegella, Patti; Tong, Angie; King, Lesley] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
[Valdimarsdottir, Heiddis B.] Mt Sinai Sch Med, New York, NY USA.
[Wood, Marie; McKinnon, Wendy] Univ Vermont, Coll Med, Vermont Canc Ctr, Familial Canc Program, Burlington, VT USA.
[Garber, Judy; McCormick, Shelley] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Kinney, Anita Y.] Univ Utah, Sch Med, Salt Lake City, UT USA.
[Kinney, Anita Y.] Huntsman Canc Inst, Salt Lake City, UT USA.
RP Schwartz, MD (reprint author), Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, 3300 Whitehaven St NW,Suite 4100, Washington, DC 20007 USA.
EM schwartm@georgetown.edu
RI Kelly, Scott/D-3195-2013;
OI Kelly, Scott/0000-0002-0375-1040; Luta, George/0000-0001-9013-2207;
Luta, George/0000-0002-4035-7632
FU National Cancer Institute [R01 CA108933, U01 CA152958, P30 CA051008];
Lombardi Comprehensive Cancer Center Biostatistics and Bioinformatics
Shared Resource; Jess and Mildred Fisher Center for Familial Cancer
Research
FX Supported by Grants No. R01 CA108933, U01 CA152958, and P30 CA051008
from the National Cancer Institute; by the Lombardi Comprehensive Cancer
Center Biostatistics and Bioinformatics Shared Resource; and by the Jess
and Mildred Fisher Center for Familial Cancer Research.
NR 54
TC 42
Z9 42
U1 2
U2 10
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAR 1
PY 2014
VL 32
IS 7
BP 618
EP +
DI 10.1200/JCO.2013.51.3226
PG 10
WC Oncology
SC Oncology
GA AC4HY
UT WOS:000332483100006
PM 24449235
ER
PT J
AU Siddiqui, JD
Loeffler, JS
Murphy, MA
AF Siddiqui, Jamal D.
Loeffler, Jay S.
Murphy, Marjorie A.
TI Response
SO JOURNAL OF NEURO-OPHTHALMOLOGY
LA English
DT Letter
C1 [Siddiqui, Jamal D.] Rhode Isl Hosp, Dept Ophthalmol, Providence, RI 02903 USA.
[Loeffler, Jay S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Murphy, Marjorie A.] Providence Vet Affairs Med Ctr, Dept Ophthalmol, Providence, RI USA.
RP Siddiqui, JD (reprint author), Rhode Isl Hosp, Dept Ophthalmol, Providence, RI 02903 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1070-8022
EI 1536-5166
J9 J NEURO-OPHTHALMOL
JI J. Neuro-Ophthal.
PD MAR
PY 2014
VL 34
IS 1
BP 102
EP 102
DI 10.1097/01.wno.0000444665.80302.c7
PG 1
WC Clinical Neurology; Ophthalmology
SC Neurosciences & Neurology; Ophthalmology
GA AB5AV
UT WOS:000331802200033
PM 24531321
ER
PT J
AU Hansen, L
Leo, MC
Chang, MF
Zucker, BL
Sasaki, A
AF Hansen, Lissi
Leo, Michael C.
Chang, Michael F.
Zucker, Betsy L.
Sasaki, Anna
TI Pain and Self-Care Behaviours in Adult Patients with End-Stage Liver
Disease: A longitudinal description
SO JOURNAL OF PALLIATIVE CARE
LA English
DT Article
DE palliative care; survival time; simple prognostic scores
ID QUALITY-OF-LIFE; INTEGRATING PALLIATIVE CARE; CANCER PAIN; PSYCHOLOGICAL
DISTRESS; TRANSPLANT CANDIDATES; MODEL; ACUPUNCTURE; MEDICATIONS;
CIRRHOSIS; SEVERITY
AB This prospective descriptive study investigated pain characteristics in 20 outpatients with end-stage liver disease (ESLD) who were approaching the end of life, described variability in pain between and within patients, and described the pharmacological and nonpharmacological pain management strategies used. The instruments we utilized were the Brief Pain Inventory (BPI) and the self-care behaviour (SCB) log for pain. Data were collected once a month over a six-month period. BPI severity of, and interference from pain mean scores ranged from 5.52 to 6.03 and 5.36 to 6.64, respectively. The top three pain-relieving behaviours reported by patients were "taking pain medication," "taking a nap," and "asking for help." Pain medication intake differed between patients who were pursuing a liver transplant and those who were not eligible for one. If we are to effectively improve care for ESLD patients, it is essential that we understand the ways in which these patients experience pain and the pain management strategies they employ.
C1 [Hansen, Lissi] Oregon Hlth & Sci Univ, Sch Nursing, SN ORD, Portland, OR 97239 USA.
[Leo, Michael C.] Kaiser Permanente, Ctr Hlth Res, Portland, OR USA.
[Chang, Michael F.; Zucker, Betsy L.; Sasaki, Anna] Portland VA Med Ctr, Portland, OR USA.
[Sasaki, Anna] Oregon Hlth & Sci Univ, Portland, OR 97239 USA.
RP Hansen, L (reprint author), Oregon Hlth & Sci Univ, Sch Nursing, SN ORD, 3455 SW US Vet Hosp Rd, Portland, OR 97239 USA.
EM hansenli@ohsu.edu
FU National Institute of Nursing Research, National Institutes of Health
(NIH) [R03 NR010614]
FX Special thanks go to the patients who participated in the study and to
Dr. Christine A. Miaskowski at the University of California, San
Francisco, for giving us permission to use the SCB log for pain. This
study was supported by research grant R03 NR010614 from the National
Institute of Nursing Research, National Institutes of Health (NIH).
NR 44
TC 0
Z9 0
U1 0
U2 11
PU CENTRE RECHERCHE INSTITUT UNIV GERIATRIE MONTREAL
PI MONTREAL
PA 4565 CHEMIN QUEEN MARY, MONTREAL, QUEBEC H3W 1W5, CANADA
SN 0825-8597
J9 J PALLIAT CARE
JI J. Palliative Care
PD SPR
PY 2014
VL 30
IS 1
BP 32
EP 40
PG 9
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA AE2HW
UT WOS:000333794900005
PM 24826441
ER
PT J
AU Greene, M
Steinman, MA
McNicholl, IR
Valcour, V
AF Greene, Meredith
Steinman, Michael A.
McNicholl, Ian R.
Valcour, Victor
TI Polypharmacy, Drug Drug Interactions, and Potentially Inappropriate
Medications in Older Adults with Human Immunodeficiency Virus Infection
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE polypharmacy; HIV infection; drug interactions; inappropriate
prescribing
ID HIV-INFECTION; ANTIRETROVIRAL THERAPY; UNITED-STATES; INDIVIDUALS;
COHORT; RISK; MEN; PREVALENCE
AB ObjectivesTo describe the frequency of medication-related problems in older adults with human immunodeficiency virus (HIV) infection.
DesignRetrospective chart review.
SettingCommunity.
ParticipantsHIV-positive individuals aged 60 and older and age- and sex-matched HIV-negative individuals.
MeasurementsTotal number of medications, potentially inappropriate medications (PIMs) according to the modified Beers Criteria, anticholinergic drug burden according to the Anticholinergic Risk Scale (ARS), and drug-drug interactions using the Lexi-Interact online drug interactions database.
ResultsOf 89 HIV-positive participants, most were Caucasian (91%) and male (94%), with a median age of 64 (range 60-82). Common comorbidities included hyperlipidemia, hypertension, and depression. Participants were taking a median of 13 medications (range 2-38), of which only a median of four were antiretrovirals. At least one PIM was prescribed in 46 participants (52%). Sixty-two (70%) participants had at least one Category D (consider therapy modification) drug-drug interaction, and 10 (11%) had a Category X (avoid combination) interaction. One-third of these interactions were between two nonantiretroviral medications. Fifteen participants (17%) had an ARS score of 3 or greater. In contrast, HIV-negative participants were taking a median of six medications, 29% had at least one PIM, and 4% had an ARS score of 3 or greater (P<.05 for each comparison, except P=.07 for anticholinergic burden).
ConclusionHIV-positive older adults have a high frequency of medication-related problems, of which a large portion is due to medications used to treat comorbid diseases. These medication issues were substantially higher than HIV-negative participants. Attention to the principles of geriatric prescribing is needed as this population ages in order to minimize complications from multiple medication use.
C1 [Greene, Meredith; Steinman, Michael A.; Valcour, Victor] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA.
[Greene, Meredith; Steinman, Michael A.] San Francisco VA Med Ctr, San Francisco, CA USA.
[McNicholl, Ian R.] Univ Calif San Francisco, San Francisco Gen Hosp, Posit Hlth Program, San Francisco, CA USA.
[McNicholl, Ian R.] Univ Calif San Francisco, Sch Pharm, San Francisco, CA 94143 USA.
[Valcour, Victor] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA.
RP Greene, M (reprint author), San Francisco VA Med Ctr, 4150 Clement St,UCSF Box VA-181G, San Francisco, CA 94121 USA.
EM meredith.greene@ucsf.edu
FU ADRC [K23-AG-032872, P50 AG023501]; UCSF CFAR [P30-AI027763]; UCSF GCRC
[UL1 RR024131]; Larry L. Hillblom Foundation; AIDS Research Institute at
UCSF; National institutes of Health (NTH) [NIA T32-AG00212]; S.D.
Bechtel, Jr. Foundation, Program for the Aging Century; National
Institute on Aging; American Federation for Aging Research
[1K23-AG030999]; NIH [AG032872]; NIH, University of California at San
Francisco-Gladstone Institute of Virology and Immunology Center for AIDS
Research [P30-AI027763]
FX This work was funded by K23-AG-032872, P50 AG023501 (ADRC, PI: Bruce
Miller), P30-AI027763 (UCSF CFAR), UL1 RR024131 (UCSF GCRC), the Larry
L. Hillblom Foundation, and the AIDS Research Institute at UCSF. Dr.
Greene receives salary support through National institutes of Health
(NTH) research training grant NIA T32-AG00212 and has received research
funding from the S.D. Bechtel, Jr. Foundation, Program for the Aging
Century. Dr. Steinman receives funding from the National Institute on
Aging and the American Federation for Aging Research (1K23-AG030999).
Dr. Valcour receives research support from NIH, including salary support
for work related to HIV and aging (AG032872). Drs. Greene and Valcour
receive research funding from the NIH, University of California at San
Francisco-Gladstone Institute of Virology and Immunology Center for AIDS
Research (P30-AI027763).
NR 35
TC 16
Z9 16
U1 5
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD MAR
PY 2014
VL 62
IS 3
BP 447
EP 453
DI 10.1111/jgs.12695
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA AC8HJ
UT WOS:000332773800005
PM 24576251
ER
PT J
AU Feng, WG
Chumley, P
Allon, M
George, J
Scott, DW
Patel, RP
Litovsky, S
Jaimes, EA
AF Feng, Wenguang
Chumley, Phillip
Allon, Michael
George, James
Scott, David W.
Patel, Rakesh P.
Litovsky, Silvio
Jaimes, Edgar A.
TI The Transcription Factor E26 Transformation-Specific Sequence-1 Mediates
Neointima Formation in Arteriovenous Fistula
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID VASCULAR ACCESS; ANGIOTENSIN-II; FACTOR ETS-1; HEMODIALYSIS-PATIENTS;
INTIMAL HYPERPLASIA; GENE-EXPRESSION; MESANGIAL CELLS; INCREASED RISK;
DNA-BINDING; MORTALITY
AB Hemodialysis vascular access dysfunction contributes to increased morbidity and mortality in hemodialysis patients. Arteriovenous fistula (AVF) is the preferred type of vascular access for hemodialysis but has high rates of dysfunction, in part because of excessive neointima formation. The transcription factor E26 transformation-specific sequence-1 (ETS-1) is a mediator of proinflammatory responses in hypertension and endovascular injury. We examined the role of ETS-1 in the formation of neointima in AVF. Right carotid artery to internal jugular vein fistulas were created in C57BL/6 mice and assigned to treatment with an ETS-1-dominant negative peptide (ETS-DN), an inactive mutant peptide (ETS-MU), or vehicle (n=6 per group). After 7 and 21 days, AVFs or contralateral internal jugular veins were processed for PCR, immunofluorescence, immunohistochemistry, and morphometry. In AVFs, ETS-1 mRNA increased 2.5-fold at 7 days and 4-fold at 21 days. By immunofluorescence, we confirmed increased expression of ETS-1 predominantly in the neointima and overlying endothelium. Similarly, ETS-1 expression increased in human AVFs compared with normal veins. In mice, ETS-DN, but not ETS-MU, reduced neointima formation at days 7 and 21 and reduced the expression of nitric oxide synthase 2, NADPH oxidase (NOX) 2, NOX4, E-selectin, and monocyte chemotactic protein-1. Shear stress increased ETS-1 phosphorylation in human umbilical vein cells in a NOX-dependent manner, demonstrating a role for reactive oxygen species in ETS-1 activation. These results unveil the role of ETS-1 as a mediator of neointima formation in AVF and may result in the development of novel strategies for the treatment of AVF dysfunction.
C1 [Feng, Wenguang; Chumley, Phillip; Allon, Michael; George, James; Jaimes, Edgar A.] Univ Alabama Birmingham, Div Nephrol, Birmingham, AL 35294 USA.
[George, James] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA.
[Scott, David W.; Patel, Rakesh P.; Litovsky, Silvio] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA.
[Jaimes, Edgar A.] Birmingham Vet Affairs Med Ctr, Res Serv, Birmingham, AL USA.
RP Jaimes, EA (reprint author), Univ Alabama Birmingham, Ziegler Res Bldg,637 1720 2nd Ave South, Birmingham, AL 35294 USA.
EM ejaimes@uab.edu
OI Patel, Rakesh/0000-0002-1526-4303
FU Veterans Affairs Administration [I01BX001073-03]; National Institutes of
Health Research [DK085027-03]; UAB-UCSD O'Brien Core Center for Kidney
Research [P30DK079337-05]
FX These studies were funded by a Merit Review Award (I01BX001073-03) and a
Program Project Award from the Veterans Affairs Administration
(IP1BX001595-01A1) to E.A.J., a National Institutes of Health Research
Grant (DK085027-03) to M.A., and the UAB-UCSD O'Brien Core Center for
Kidney Research Grant (P30DK079337-05).
NR 41
TC 5
Z9 5
U1 0
U2 1
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 MAR
PY 2014
VL 25
IS 3
BP 475
EP 487
DI 10.1681/ASN.2013040424
PG 13
WC Urology & Nephrology
SC Urology & Nephrology
GA AB9YB
UT WOS:000332150500009
PM 24203999
ER
PT J
AU Iaquinto, JM
Tsai, R
Haynor, DR
Fassbind, MJ
Sangeorzan, BJ
Ledoux, WR
AF Iaquinto, Joseph M.
Tsai, Richard
Haynor, David R.
Fassbind, Michael J.
Sangeorzan, Bruce J.
Ledoux, William R.
TI Marker-based validation of a biplane fluoroscopy system for quantifying
foot kinematics
SO MEDICAL ENGINEERING & PHYSICS
LA English
DT Article
DE Biplane fluoroscopy; X-ray; Foot; Biomechanics
ID MODEL
AB Introduction: Radiostereometric analysis has demonstrated its capacity to track precise motion of the bones within a subject during motion. Existing devices for imaging the body in two planes are often custom built systems: we present here the design and marker-based validation of a system that has been optimized to image the foot during gait.
Methods: Mechanical modifications were made to paired BV Pulsera C-arms (Philips Medical Systems) to allow unfettered gait through the imaging area. Image quality improvements were obtained with high speed cameras and the correction of image distorting artifacts. To assess the system's accuracy, we placed beads at known locations throughout the imaging field, and used post processing software to calculate their apparent locations.
Results: Distortion correction reduced overall RMS error from 6.56 mm to 0.17 mm. When tracking beads in static images a translational accuracy of 0.094 +/- 0.081 mm and rotational accuracy of 0.083 +/- 0.068 degrees was determined. In dynamic trials simulating speeds seen during walking, accuracy was 0.126 +/- 0.122 mm.
Discussion: The accuracies and precisions found are within the reported ranges from other such systems. With the completion of marker-based validation, we look to model-based validation of the foot during gait. Published by Elsevier Ltd on behalf of IPEM.
C1 [Iaquinto, Joseph M.; Tsai, Richard; Fassbind, Michael J.; Sangeorzan, Bruce J.; Ledoux, William R.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, RR&D Ctr Excellence Limb Loss Prevent & Prosthet, Seattle, WA USA.
[Iaquinto, Joseph M.; Ledoux, William R.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA.
[Haynor, David R.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA.
[Sangeorzan, Bruce J.; Ledoux, William R.] Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA.
RP Ledoux, WR (reprint author), VA Puget Sound, Ms 151,1660 S Columbian Way, Seattle, WA 98108 USA.
EM wrledoux@u.washington.edu
RI Ledoux, William/K-6815-2015
OI Ledoux, William/0000-0003-4982-7714
FU Department of Veterans Affairs Rehabilitation Research and Development
[A4843C, F7468R]; Magnuson Award
FX This research was funded in part by the Department of Veterans Affairs
Rehabilitation Research and Development grants A4843C, F7468R and the
Magnuson Award. The study sponsor has no role in the study design, in
the collection, analysis and interpretation of data; in the writing of
the manuscript; and in the decision to submit the manuscript for
publication.
NR 12
TC 5
Z9 5
U1 1
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1350-4533
EI 1873-4030
J9 MED ENG PHYS
JI Med. Eng. Phys.
PD MAR
PY 2014
VL 36
IS 3
BP 391
EP 396
DI 10.1016/j.medengphy.2013.08.013
PG 6
WC Engineering, Biomedical
SC Engineering
GA AE5DT
UT WOS:000334008700015
PM 24075068
ER
PT J
AU Yao, M
Gu, C
Doyle, FJ
Zhu, H
Redmond, RW
Kochevar, IE
AF Yao, Min
Gu, Chuan
Doyle, Francis J., Jr.
Zhu, Hong
Redmond, Robert W.
Kochevar, Irene E.
TI Why is Rose Bengal More Phototoxic to Fibroblasts In Vitro Than In Vivo?
SO PHOTOCHEMISTRY AND PHOTOBIOLOGY
LA English
DT Article
ID PHOTODYNAMIC THERAPY; SINGLET OXYGEN; FLUENCE RATE; INDUCED APOPTOSIS;
CELL-SURVIVAL; TUMOR; LIGHT; TISSUE; MODEL; SKIN
AB Photosensitized protein cross-linking has been recently developed to seal wounds and strengthen tissue. Although the photosensitizing dye, Rose Bengal (RB), is phototoxic to cultured cells, cytotoxicity does not accompany RB-photosensitized tissue repair in vivo. We investigated whether the environment surrounding cells in tissue or the high irradiances used for photo-cross-linking inhibited RB phototoxicity. Fibroblasts (FB) grown within collagen gels to mimic a tissue environment and monolayer cultured FB were treated with RB (0.01-1mm) and the high 532nm laser irradiances used in vivo for tissue repair (0.10-0.50Wcm(-2)). Monolayer FB were substantially more sensitive to RB photosensitization: the LD50 was >200-fold lower than that in collagen gels. Collagen gel protection was associated with increased Akt phosphorylation, a prosurvival pathway. RB phototoxicity in collagen gels was 25-fold greater at low (0.030Wcm(-2)) that at high (0.50Wcm(-2)) irradiances. Oxygen depletion at high irradiance only partially accounted for the irradiance dependence of phototoxicity as replacing air with nitrogen only increased the LD50 by four-fold in monolayers. These results indicate that the lack of RB phototoxicity during in vivo tissue repair results from upregulation of prosurvival pathways in tissue cells, oxygen depletion and irradiance-dependent RB photochemistry.
C1 [Yao, Min; Gu, Chuan; Doyle, Francis J., Jr.; Zhu, Hong; Redmond, Robert W.; Kochevar, Irene E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02115 USA.
RP Kochevar, IE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02115 USA.
EM kochevar@helix.mgh.harvard.edu
NR 45
TC 5
Z9 5
U1 2
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0031-8655
EI 1751-1097
J9 PHOTOCHEM PHOTOBIOL
JI Photochem. Photobiol.
PD MAR
PY 2014
VL 90
IS 2
BP 297
EP 305
DI 10.1111/php.12215
PG 9
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA AC8HP
UT WOS:000332774400007
PM 24266530
ER
PT J
AU Cuijpers, P
Turner, EH
Mohr, DC
Hofmann, SG
Andersson, G
Berking, M
Coyne, J
AF Cuijpers, P.
Turner, E. H.
Mohr, D. C.
Hofmann, S. G.
Andersson, G.
Berking, M.
Coyne, J.
TI Comparison of psychotherapies for adult depression to pill placebo
control groups: a meta-analysis
SO PSYCHOLOGICAL MEDICINE
LA English
DT Review
DE placebo; psychotherapy; Depression; meta-analysis
ID RANDOMIZED CONTROLLED-TRIAL; PRIMARY-CARE PATIENTS; COGNITIVE THERAPY;
MAJOR DEPRESSION; ANTIDEPRESSANT MEDICATION; PSYCHOLOGICAL TREATMENTS;
BEHAVIORAL ACTIVATION; MINOR DEPRESSION; PUBLICATION BIAS; FOLLOW-UP
AB Background
The effects of antidepressants for treating depressive disorders have been overestimated because of selective publication of positive trials. Reanalyses that include unpublished trials have yielded reduced effect sizes. This in turn has led to claims that antidepressants have clinically insignificant advantages over placebo and that psychotherapy is therefore a better alternative. To test this, we conducted a meta-analysis of studies comparing psychotherapy with pill placebo.
Method
Ten 10 studies comparing psychotherapies with pill placebo were identified. In total, 1240 patients were included in these studies. For each study, Hedges' g was calculated. Characteristics of the studies were extracted for subgroup and meta-regression analyses.
Results
The effect of psychotherapy compared to pill placebo at post-test was g=0.25 [95% confidence interval (CI) 0.14-0.36, I (2)=0%, 95% CI 0-58]. This effect size corresponds to a number needed to treat (NNT) of 7.14 (95% CI 5.00-12.82). The psychotherapy conditions scored 2.66 points lower on the Hamilton Depression Rating Scale (HAMD) than the placebo conditions, and 3.20 points lower on the Beck Depression Inventory (BDI). Some indications for publication bias were found (two missing studies). We found no significant differences between subgroups of the studies and in meta-regression analyses we found no significant association between baseline severity and effect size.
Conclusions
Although there are differences between the role of placebo in psychotherapy and pharmacotherapy research, psychotherapy has an effect size that is comparable to that of antidepressant medications. Whether these effects should be deemed clinically relevant remains open to debate.
C1 [Cuijpers, P.] Vrije Univ Amsterdam, Dept Clin Psychol, NL-1081 BT Amsterdam, Netherlands.
[Cuijpers, P.] EMGO Inst Hlth & Care Res, Amsterdam, Netherlands.
[Turner, E. H.] Portland VA Med Ctr, Behav Hlth & Neurosci Div, Portland, OR USA.
[Turner, E. H.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA.
[Turner, E. H.] Oregon Hlth & Sci Univ, Dept Pharmacol, Portland, OR 97201 USA.
[Mohr, D. C.] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA.
[Hofmann, S. G.] Boston Univ, Dept Psychol, Boston, MA 02215 USA.
[Andersson, G.] Linkoping Univ, Swedish Inst Disabil Res, Dept Behav Sci & Learning, S-58183 Linkoping, Sweden.
[Andersson, G.] Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, Stockholm, Sweden.
[Berking, M.] Univ Marburg, Dept Clin Psychol, D-35032 Marburg, Germany.
[Coyne, J.] Univ Groningen, Univ Med Ctr Groningen, Dept Hlth Sci, Hlth Psychol Sect, Groningen, Netherlands.
RP Cuijpers, P (reprint author), Vrije Univ Amsterdam, Dept Clin Psychol, Van der Boechorststr 1, NL-1081 BT Amsterdam, Netherlands.
EM p.cuijpers@vu.nl
RI Andersson, Gerhard/J-8529-2012; Hofmann, Stefan/B-8769-2014;
OI Andersson, Gerhard/0000-0003-4753-6745; Hofmann,
Stefan/0000-0002-3548-9681; Cuijpers, Pim/0000-0001-5497-2743
NR 46
TC 22
Z9 22
U1 4
U2 30
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 MAR
PY 2014
VL 44
IS 4
BP 685
EP 695
DI 10.1017/S0033291713000457
PG 11
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA AD0WJ
UT WOS:000332954700003
PM 23552610
ER
PT J
AU Bird, GH
Gavathiotis, E
LaBelle, JL
Katz, SG
Walensky, LD
AF Bird, Greg H.
Gavathiotis, Evripidis
LaBelle, James L.
Katz, Samuel G.
Walensky, Loren D.
TI Distinct BimBH3 (BimSAHB) Stapled Peptides for Structural and Cellular
Studies
SO ACS CHEMICAL BIOLOGY
LA English
DT Letter
ID STABILIZED ALPHA-HELICES; BH3 HELIX; PROAPOPTOTIC BAX; BCL-2 DOMAINS;
ACTIVATION; APOPTOSIS
AB Hydrocarbon stapling is a chemical approach to restoring and fortifying the natural a-helical structure of peptides that otherwise unfold when taken out of context from the host protein. By iterating the peptide sequence, staple type, and sites of insertion, discrete compositions can be generated to suit a diversity of biochemical, structural, proteomic, cellular, and drug development applications. Here, we reinforce key design considerations to avoid pitfalls and maximize progress when applying stapled peptides in chemistry and biology research.
C1 [Bird, Greg H.; Walensky, Loren D.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA.
[Gavathiotis, Evripidis] Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA.
[LaBelle, James L.] Univ Chicago, Comer Childrens Hosp, Dept Pediat Hematol Oncol Stem Cell Transplantat, Chicago, IL 60637 USA.
[Katz, Samuel G.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA.
RP Walensky, LD (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA.
EM Loren_Walensky@dfci.harvard.edu
FU NCI NIH HHS [5R01CA050239, K08 CA151450, R01 CA050239, R01 CA178394];
NIGMS NIH HHS [5R01GM090299, R01 GM090299]
NR 22
TC 38
Z9 38
U1 1
U2 21
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1554-8929
EI 1554-8937
J9 ACS CHEM BIOL
JI ACS Chem. Biol.
PD MAR
PY 2014
VL 9
IS 3
BP 831
EP 837
DI 10.1021/cb4003305
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AD7WI
UT WOS:000333477300031
PM 24358963
ER
PT J
AU Lee, S
Koo, H
Na, JH
Han, SJ
Min, HS
Lee, SJ
Kim, SH
Yun, SH
Jeong, SY
Kwon, IC
Choi, K
Kim, K
AF Lee, Sangmin
Koo, Heebeom
Na, Jin Hee
Han, Seung Jin
Min, Hyun Su
Lee, So Jin
Kim, Sun Hwa
Yun, Seok Hyun
Jeong, Seo Young
Kwon, Ick Chan
Choi, Kuiwon
Kim, Kwangmeyung
TI Chemical Tumor-Targeting of Nanoparticles Based on Metabolic
Glycoengineering and Click Chemistry
SO ACS NANO
LA English
DT Article
DE nanoparticle; click chemistry; metabolic glycoengineering;
tumor-targeting; drug delivery
ID GLYCOL CHITOSAN NANOPARTICLES; IN-VIVO; MULTIFUNCTIONAL NANOPARTICLES;
DRUG-DELIVERY; BIOORTHOGONAL CHEMISTRY; CANCER-THERAPY; COPPER-FREE;
REAL-TIME; EFFICACY; GLYCANS
AB Tumor-targeting strategies for nanoparticles have been predominantly based on optimization of physical properties or conjugation with biological ligands. However, their tumor-targeting abilities remain limited and insufficient. Furthermore, traditional biological binding molecules have intrinsic limitations originating from the limited amount of cellular receptors and the heterogeneity of tumor cells. Our two-step in vivo tumor-targeting strategy for nanoparticles is based on metabolic glycoengineering and click chemistry. First, an intravenous injection of precursor-loaded glycol chitosan nanoparticles generates azide groups on tumor tissue specifically by the enhanced permeation and retention (EPR) effect followed by metabolic glycoengineering. These 'receptor-like' chemical groups then enhance the tumor-targeting ability of drug-containing nanoparticles by copper-free click chemistry in vivo during a second intravenous injection. The advantage of this protocol over traditional binding molecules is that there are significantly more binding molecules on the surface of most tumor cells regardless of cell type. The subsequent enhanced tumor-targeting ability can significantly enhance the cancer therapeutic efficacy in animal studies.
C1 [Lee, Sangmin; Koo, Heebeom; Na, Jin Hee; Han, Seung Jin; Min, Hyun Su; Lee, So Jin; Kim, Sun Hwa; Kwon, Ick Chan; Choi, Kuiwon; Kim, Kwangmeyung] Korea Inst Sci & Technol, Ctr Theragnosis, Biomed Res Inst, Seoul 136791, South Korea.
[Lee, Sangmin; Na, Jin Hee; Han, Seung Jin; Jeong, Seo Young] Kyung Hee Univ, Dept Life & Nanopharmaceut Sci, Seoul 130701, South Korea.
[Koo, Heebeom; Yun, Seok Hyun] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Cambridge, MA 02139 USA.
[Kwon, Ick Chan] Korea Univ, KU KIST Sch, Seoul 136701, South Korea.
RP Choi, K (reprint author), Korea Inst Sci & Technol, Ctr Theragnosis, Biomed Res Inst, 39-1 Hawolgok Dong, Seoul 136791, South Korea.
EM choi@kist.re.kr; kim@kist.re.kr
FU Global Research Laboratory Project [NRF-2013K1A1A2032346,
NRF-2013K1A1A2A02050115]; Fusion Technology Project [2009-0081876];
Intramural Research Program (Theragnosis) of KIST
FX This study was funded by the Global Research Laboratory Project
(NRF-2013K1A1A2032346 & NRF-2013K1A1A2A02050115), the Fusion Technology
Project (2009-0081876), and the Intramural Research Program
(Theragnosis) of KIST.
NR 49
TC 24
Z9 24
U1 7
U2 78
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1936-0851
EI 1936-086X
J9 ACS NANO
JI ACS Nano
PD MAR
PY 2014
VL 8
IS 3
BP 2048
EP 2063
DI 10.1021/nn406584y
PG 16
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary
SC Chemistry; Science & Technology - Other Topics; Materials Science
GA AD8TU
UT WOS:000333539400020
PM 24499346
ER
PT J
AU Olsen, RW
Li, GD
Wallner, M
Trudell, JR
Bertaccini, EJ
Lindahl, E
Miller, KW
Alkana, RL
Davies, DL
AF Olsen, Richard W.
Li, Guo-Dong
Wallner, Martin
Trudell, James R.
Bertaccini, Edward J.
Lindahl, Erik
Miller, Keith W.
Alkana, Ronald L.
Davies, Daryl L.
TI Structural Models of Ligand-Gated Ion Channels: Sites of Action for
Anesthetics and Ethanol
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE GABA(A) Receptors; GluCl Pentameric Ion Channels; ELIC; GLIC; Loop 2;
Ethanol Sites of Action
ID NICOTINIC ACETYLCHOLINE-RECEPTOR; GABA(A) RECEPTOR; GLYCINE RECEPTORS;
GENERAL-ANESTHETICS; BINDING-SITES; A RECEPTORS; DELTA-SUBUNIT; ALCOHOL;
ETOMIDATE; AGONIST
AB The molecular mechanism(s) of action of anesthetic, and especially, intoxicating doses of alcohol (ethanol [EtOH]) have been of interest even before the advent of the Research Society on Alcoholism. Recent physiological, genetic, and biochemical studies have pin-pointed molecular targets for anesthetics and EtOH in the brain as ligand-gated ion channel (LGIC) membrane proteins, especially the pentameric (5 subunit) Cys-loop superfamily of neurotransmitter receptors including nicotinic acetylcholine (nAChRs), GABA(A) (GABA(A)Rs), and glycine receptors (GlyRs). The ability to demonstrate molecular and structural elements of these proteins critical for the behavioral effects of these drugs on animals and humans provides convincing evidence for their role in the drugs' actions. Amino acid residues necessary for pharmacologically relevant allosteric modulation of LGIC function by anesthetics and EtOH have been identified in these channel proteins. Site-directed mutagenesis revealed potential allosteric modulatory sites in both the trans-membrane domain (TMD) and extracellular domain (ECD). Potential sites of action and binding have been deduced from homology modeling of other LGICs with structures known from crystallography and cryo-electron microscopy studies. Direct information about ligand binding in the TMD has been obtained by photoaffinity labeling, especially in GABA(A)Rs. Recent structural information from crystallized procaryotic (ELIC and GLIC) and eukaryotic (GluCl) LGICs allows refinement of the structural models including evaluation of possible sites of EtOH action.
C1 [Olsen, Richard W.; Li, Guo-Dong; Wallner, Martin] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA.
[Olsen, Richard W.; Li, Guo-Dong] Univ Calif Los Angeles, David Geffen Sch Med, Dept Anesthesiol, Los Angeles, CA 90095 USA.
[Trudell, James R.; Bertaccini, Edward J.] Stanford Univ, Sch Med, Dept Anesthesia, Stanford, CA 94305 USA.
[Lindahl, Erik] KTH Royal Inst Technol, Stockholm, Sweden.
[Miller, Keith W.] Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Boston, MA USA.
[Alkana, Ronald L.; Davies, Daryl L.] Univ So Calif, Sch Pharm, Los Angeles, CA USA.
RP Olsen, RW (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Room CHS 23-120,650 Young Dr South, Los Angeles, CA 90095 USA.
EM rolsen@mednet.ucla.edu
RI Wallner, Martin/B-8322-2009; Davies, Daryl/P-1137-2016
OI Wallner, Martin/0000-0003-4134-8946; Davies, Daryl/0000-0003-2940-7739
FU NIAAA [AA007680, AA013378]; NIGMS [GM 58448]; Department of Anesthesia,
Critical Care and Pain Medicine, Massachusetts General Hospital; USC
School of Pharmacy
FX This work was supported, in whole or in part, by NIAAA grants AA007680
to RWO and AA013378 to JRT; NIGMS (GM 58448) and the Department of
Anesthesia, Critical Care and Pain Medicine, Massachusetts General
Hospital to KWM; and USC School of Pharmacy to RLA and DLD.
NR 53
TC 18
Z9 18
U1 0
U2 20
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 MAR
PY 2014
VL 38
IS 3
BP 595
EP 603
DI 10.1111/acer.12283
PG 9
WC Substance Abuse
SC Substance Abuse
GA AC8BO
UT WOS:000332758200001
PM 24164436
ER
PT J
AU Tartaglione, EV
Derleth, M
Yu, L
Ioannou, GN
AF Tartaglione, Erica V.
Derleth, Mark
Yu, Lei
Ioannou, George N.
TI Can Computerized Brain Training Games be Used to Identify Early
Cognitive Impairment in Cirrhosis?
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
ID MINIMAL HEPATIC-ENCEPHALOPATHY; INHIBITORY CONTROL TEST;
LIVER-TRANSPLANTATION; TESTS; DIAGNOSIS; TASK
AB OBJECTIVES: We evaluated whether commercially available, computerized "brain-training" games can be used to identify subtle cognitive impairments in patients with cirrhosis.
METHODS: We compared patients with cirrhosis who did not have overt encephalopathy (n = 31), patients with pre-cirrhotic chronic liver disease (n = 28), and normal controls without liver disease (n = 16) with respect to their scores on the number connection test-A (NCT-A), the Inhibitory Control Test (ICT), and five, short (similar to 2.5 min), brain-training games that were administered on an Apple iPad and tested different cognitive domains.
RESULTS: Patients with cirrhosis had similar scores to patients with pre-cirrhotic liver disease and slightly worse scores than normal controls in the NCT-A and the ICT, although these differences were not statistically significant. In contrast, patients with cirrhosis had significantly worse scores than patients with pre-cirrhotic liver disease and even more so than normal controls in all five of the brain-training games. After adjustment for age and educational attainment, these differences remained significant for two of the tests, "Color Match" which is a version of the Stroop test and measures selective attention, and "Memory Matrix", which measures visuospatial memory. The area under the receiver operating characteristic curve discriminating cirrhosis from pre-cirrhotic liver disease was 0.56 (95% confidence interval (CI) 0.41-0.72) for the ICT and 0.58 (95% CI 0.43-0.73) for the NCT-A, indicating no discrimination, while it was 0.75 (95% CI 0.63-0.87) for "Color Match" and 0.77 (95% CI 0.64-0.90) for "Memory Matrix", indicating good discrimination.
CONCLUSIONS: Short, brain-training games administered on an iPad can be used as psychometric tests to detect subtle cognitive impairments in patients with cirrhosis without overt encephalopathy that could not be detected by the NCT-A or the ICT.
C1 [Tartaglione, Erica V.; Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Res & Dev, Seattle, WA 98108 USA.
[Derleth, Mark; Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Dept Med, Seattle, WA 98108 USA.
[Derleth, Mark; Yu, Lei; Ioannou, George N.] Univ Washington, Dept Med, Div Gastroenterol, Seattle, WA USA.
RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Gastroenterol, S-111 Gastro,1660 S Columbian Way, Seattle, WA 98108 USA.
EM georgei@medicine.washington.edu
FU Research Enhancement Award Program (REAP) by the Veterans Affairs Office
of Research and Development
FX This study was supported by a Research Enhancement Award Program (REAP)
by the Veterans Affairs Office of Research and Development (awarded to
G.N.I.).
NR 31
TC 1
Z9 1
U1 1
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
EI 1572-0241
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD MAR
PY 2014
VL 109
IS 3
BP 316
EP 323
DI 10.1038/ajg.2013.306
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AD4RX
UT WOS:000333239300002
PM 24594947
ER
PT J
AU Ananthakrishnan, AN
Huang, HL
Nguyen, DD
Sauk, J
Yajnik, V
Xavier, RJ
AF Ananthakrishnan, Ashwin N.
Huang, Hailiang
Nguyen, Deanna D.
Sauk, Jenny
Yajnik, Vijay
Xavier, Ramnik J.
TI Differential Effect of Genetic Burden on Disease Phenotypes in Crohn's
Disease and Ulcerative Colitis: Analysis of a North American Cohort
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
ID INFLAMMATORY-BOWEL-DISEASE; IBD; PREVALENCE; MECHANISMS; VARIANTS;
GENOTYPE; THERAPY; SAFETY; NOD2; RISK
AB OBJECTIVES: Crohn' s disease (CD) and ulcerative colitis (UC) are chronic immunologically mediated diseases with a progressive relapsing remitting course. There is considerable heterogeneity in disease course and accurate prediction of natural history has been challenging. The phenotypic implication of increasing genetic predisposition to CD or UC is unknown.
METHODS: The data source for our study was a prospective cohort of CD and UC patients recruited from a tertiary referral center. All patients underwent genotyping on the Illumina Immunochip. A genetic risk score (GRS) incorporating strength of association (log odds ratio) and allele dose for each of the 163 infl ammatory bowel disease (IBD) risk loci was calculated and phenotypic associations examined across GRS quartiles.
RESULTS: Our study cohort included 1,105 patients (697 CD, 408 UC). Increasing genetic burden was associated with earlier age of diagnosis of CD (P-trend = 0.008). Patients in the highest GRS quartile were likely to develop disease 5 years earlier than those in the lowest quartile. Increasing genetic burden was also associated with ileal involvement in CD (P-trend < 0.0001). The effect of genetic burden was independent of the NOD2 locus and was stronger among those with no NOD2 variants, and in never smokers. UC patients with an involved first-degree relative had a higher genetic burden, but GRS was not associated with disease phenotype in UC.
CONCLUSIONS: Increasing genetic burden is associated with early age of diagnosis in CD, but not UC. The expanded panel of IBD risk loci explains only a fraction of variance of disease phenotype, suggesting limited clinical utility of genetics in predicting natural history.
C1 [Ananthakrishnan, Ashwin N.; Nguyen, Deanna D.; Sauk, Jenny; Yajnik, Vijay; Xavier, Ramnik J.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Ananthakrishnan, Ashwin N.; Nguyen, Deanna D.; Sauk, Jenny; Yajnik, Vijay; Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA USA.
[Huang, Hailiang] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Huang, Hailiang; Xavier, Ramnik J.] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, Div Gastroenterol, 165 Cambridge St ,9th Floor, Boston, MA 02114 USA.
EM aananthakrishnan@partners.org
OI Huang, Hailiang/0000-0003-1461-5762
FU National Institutes of Health (NIH) [P30 DK043351, K23 DK097142, U01
DK062432, R01 DK064869]
FX This work is supported by the National Institutes of Health (NIH) (P30
DK043351) to the Center for Study of Inflammatory Bowel Diseases. A.N.
Ananthakrishnan is supported in part by a grant from the National
Institutes of Health (K23 DK097142). R.J. Xavier is supported by grants
U01 DK062432 and R01 DK064869 from the NIH.
NR 25
TC 26
Z9 26
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
EI 1572-0241
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD MAR
PY 2014
VL 109
IS 3
BP 395
EP 400
DI 10.1038/ajg.2013.464
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AD4RX
UT WOS:000333239300012
PM 24419484
ER
PT J
AU Brawman-Mintzer, O
Durkalski, V
Wu, Q
Romagnuolo, J
Fogel, E
Tarnasky, P
Aliperti, G
Freeman, M
Kozarek, R
Jamidar, P
Wilcox, M
Elta, G
Orrell, K
Wood, A
Mauldin, P
Serrano, J
Drossman, D
Robuck, P
Cotton, P
AF Brawman-Mintzer, Olga
Durkalski, Valerie
Wu, Qi
Romagnuolo, Joseph
Fogel, Evan
Tarnasky, Paul
Aliperti, Giuseppe
Freeman, Martin
Kozarek, Richard
Jamidar, Priya
Wilcox, Mel
Elta, Grace
Orrell, Kyle
Wood, April
Mauldin, Patrick
Serrano, Jose
Drossman, Douglas
Robuck, Patricia
Cotton, Peter
TI Psychosocial Characteristics and Pain Burden of Patients With Suspected
Sphincter of Oddi Dysfunction in the EPISOD Multicenter Trial
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; IRRITABLE-BOWEL-SYNDROME; FUNCTIONAL
GASTROINTESTINAL DISORDERS; NATIONAL-COMORBIDITY-SURVEY; SELF-REPORTED
ABUSE; FINDINGS TYPE-I; ABDOMINAL-PAIN; PHYSICAL ABUSE; HEALTH-STATUS;
DSM-IV
AB OBJECTIVES: Patients with several painful functional gastrointestinal disorders (FGIDs) are reported to have a high prevalence of psychosocial disturbance. These aspects have not been studied extensively in patients with suspected Sphincter of Oddi dysfunction (SOD).
METHODS: A total of 214 patients with post-cholecystectomy pain and suspected SOD were enrolled in seven US centers in a multicenter-randomized trial (Evaluating Predictors and Interventions in Sphincter of Oddi Dysfunction). Baseline assessments included pain descriptors and burden, structured psychosocial assessments of anxiety/depression, coping, trauma, and health-related quality of life. Patients with high levels of depression, suicidal ideation, or psychosis were excluded.
RESULTS: The study population (92% female, mean age 38) reported anxiety (9%), depression (8%), past sexual trauma (18%), and physical abuse (10%). Of the total screened population (n = 1460), 3.9% of the patients were excluded because of the presence of defined severe psychological problems. The mean medical outcomes study short-form-36 (SF-36) physical and mental composite scores were 38.70 (s.d. = 7.89) and 48.74 (s.d. = 9.60), respectively. Most subjects reported symptoms of other FGIDs. There were no correlations between the extent of the pain burden in the 3 months before enrollment and the baseline anxiety scores or victimization history. However, those with greater pain burden were significantly more depressed. There were no meaningful differences in the psychosocial parameters in subjects with or without irritable bowel, and those who had cholecystectomy for stones or functional gallbladder disease. Those declining randomization were comparable to those randomized.
CONCLUSIONS: Psychosocial comorbidity in SOD is high. However, it does not appear to differ significantly from that reported in surveys of age-and gender-matched general populations, and may be lower than reported with other FGIDs.
C1 [Brawman-Mintzer, Olga; Durkalski, Valerie; Wu, Qi; Romagnuolo, Joseph; Orrell, Kyle; Wood, April; Mauldin, Patrick; Cotton, Peter] Med Univ S Carolina, Ctr Digest Dis, Charleston, SC 29425 USA.
[Brawman-Mintzer, Olga] Ralph H Johnson VAMC, Charleston, SC USA.
[Fogel, Evan] Indiana Univ, Indianapolis, IN 46204 USA.
[Tarnasky, Paul] Methodist Dallas Med Ctr, Dallas, TX USA.
[Aliperti, Giuseppe] Midwest Therapeut Endoscopy Consultants, St Louis, MO USA.
[Freeman, Martin] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA.
[Kozarek, Richard] Virginia Mason Med Ctr, Seattle, WA 98101 USA.
[Jamidar, Priya] Yale Univ, Newhaven, CT USA.
[Wilcox, Mel] Univ Alabama Birmingham, Birmingham, AL USA.
[Elta, Grace] Univ Michigan, Ann Arbor, MI 48109 USA.
[Serrano, Jose; Robuck, Patricia] NIDDK, Bethesda, MD 20892 USA.
[Drossman, Douglas] Univ N Carolina, Chapel Hill, NC USA.
[Drossman, Douglas] Drossman Gastroenterol PLLC, Chapel Hill, NC USA.
RP Cotton, P (reprint author), Med Univ S Carolina, Ctr Digest Dis, 25 Courtney Dr,ART 7100A,MSC 290, Charleston, SC 29425 USA.
EM cottonp@musc.edu
FU NIDDK [U01 DK074739]
FX This work was funded by NIDDK, study number U01 DK074739.
NR 39
TC 10
Z9 10
U1 4
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
EI 1572-0241
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD MAR
PY 2014
VL 109
IS 3
BP 436
EP 442
DI 10.1038/ajg.2013.467
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AD4RX
UT WOS:000333239300017
PM 24445573
ER
PT J
AU Eikermann, M
Melo, MFV
AF Eikermann, Matthias
Melo, Marcos F. Vidal
TI Therapeutic Range of Spontaneous Breathing during Mechanical Ventilation
SO ANESTHESIOLOGY
LA English
DT Editorial Material
ID ACUTE LUNG INJURY; MUSCLE PARALYSIS; DIAPHRAGM; DYSFUNCTION; WEAKNESS;
SUPPORT; UNIT
C1 [Eikermann, Matthias; Melo, Marcos F. Vidal] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02115 USA.
[Eikermann, Matthias] Dusiburg Essen Univ, Univ Klinikum Essen, Klin Anaesthesiol & Intens Med, Essen, Germany.
RP Eikermann, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02115 USA.
EM meikermann@partners.org
FU NHLBI NIH HHS [R01 HL086827, R01 HL121228]
NR 21
TC 3
Z9 4
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-3022
EI 1528-1175
J9 ANESTHESIOLOGY
JI Anesthesiology
PD MAR
PY 2014
VL 120
IS 3
BP 536
EP 539
DI 10.1097/ALN.0000000000000126
PG 4
WC Anesthesiology
SC Anesthesiology
GA AC9FR
UT WOS:000332840300007
PM 24424072
ER
PT J
AU Musch, G
Winkler, T
Harris, RS
Melo, MFV
Wellman, TJ
de Prost, N
Kradin, RL
Venegas, JG
AF Musch, Guido
Winkler, Tilo
Harris, R. Scott
Melo, Marcos F. Vidal
Wellman, Tyler J.
de Prost, Nicolas
Kradin, Richard L.
Venegas, Jose G.
TI Lung [ F-18] fluorodeoxyglucose Uptake and Ventilation-Perfusion
Mismatch in the Early Stage of Experimental Acute Smoke Inhalation
SO ANESTHESIOLOGY
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; PEROXYNITRITE DECOMPOSITION CATALYST;
BRONCHIAL ARTERY; OVINE MODEL; MECHANICAL VENTILATION; REGIONAL
VENTILATION; GLUCOSE-UTILIZATION; METABOLIC-ACTIVITY;
PULMONARY-FUNCTION; COMBINED BURN
AB Background: Acute lung injury occurs in a third of patients with smoke inhalation injury. Its clinical manifestations usually do not appear until 48-72 h after inhalation. Identifying inflammatory changes that occur in pulmonary parenchyma earlier than that could provide insight into the pathogenesis of smoke-induced acute lung injury. Furthermore, noninvasive measurement of such changes might lead to earlier diagnosis and treatment. Because glucose is the main source of energy for pulmonary inflammatory cells, the authors hypothesized that its pulmonary metabolism is increased shortly after smoke inhalation, when classic manifestations of acute lung injury are not yet expected.
Methods: In five sheep, the authors induced unilateral injury with 48 breaths of cotton smoke while the contralateral lung served as control. The authors used positron emission tomography with: (1) [F-18]fluorodeoxyglucose to measure metabolic activity of pulmonary inflammatory cells; and (2) [N-13]nitrogen in saline to measure shunt and ventilation-perfusion distributions separately in the smoke-exposed and control lungs.
Results: The pulmonary [F-18]fluorodeoxyglucose uptake rate was increased at 4 h after smoke inhalation (mean SD: 0.0031 +/- 0.0013 vs. 0.0026 +/- 0.0010 min(-1); P < 0.05) mainly as a result of increased glucose phosphorylation. At this stage, there was no worsening in lung aeration or shunt. However, there was a shift of perfusion toward units with lower ventilation-to-perfusion ratio (mean ratio +/- SD: 0.82 +/- 0.10 vs. 1.12 +/- 0.02; P < 0.05) and increased heterogeneity of the ventilation-perfusion distribution (mean +/- SD: 0.21 +/- 0.07 vs. 0.13 +/- 0.01; P < 0 .05).
Conclusion: Using noninvasive imaging, the authors demonstrated that increased pulmonary [F-18]fluorodeoxyglucose uptake and ventilation-perfusion mismatch occur early after smoke inhalation.
C1 [Musch, Guido; Winkler, Tilo; Melo, Marcos F. Vidal; Wellman, Tyler J.; de Prost, Nicolas; Venegas, Jose G.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Harris, R. Scott] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA.
[Kradin, Richard L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Kradin, Richard L.] Harvard Univ, Sch Med, Boston, MA USA.
RP Musch, G (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, GRJ-4-418,55 Fruit St, Boston, MA 02114 USA.
EM gmusch@partners.org
RI Winkler, Tilo/B-5337-2009;
OI Winkler, Tilo/0000-0002-7276-5550; de Prost, Nicolas/0000-0002-4833-4320
FU Shriners Hospitals for Children, Boston, Massachusetts [8895]; National
Institutes of Health Grant, Bethesda, Maryland [R01HL094639]
FX Supported by a Research Grant 8895, from Shriners Hospitals for
Children, Boston, Massachusetts, and by National Institutes of Health
Grant R01HL094639, Bethesda, Maryland.
NR 58
TC 5
Z9 5
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0003-3022
EI 1528-1175
J9 ANESTHESIOLOGY
JI Anesthesiology
PD MAR
PY 2014
VL 120
IS 3
BP 683
EP 693
DI 10.1097/01.anes.0000435742.04859.e8
PG 11
WC Anesthesiology
SC Anesthesiology
GA AC9FR
UT WOS:000332840300021
PM 24051392
ER
PT J
AU Gardner, RC
Yaffe, K
AF Gardner, Raquel C.
Yaffe, Kristine
TI Traumatic brain injury may increase risk of young onset dementia
SO ANNALS OF NEUROLOGY
LA English
DT Editorial Material
ID ALZHEIMERS-DISEASE; HEAD-INJURY; PROPAGATION; POPULATION; CONCUSSION;
PROTEINS; FIBRILS; TAU
C1 [Gardner, Raquel C.; Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Gardner, Raquel C.] San Francisco Vet Adm Med Ctr, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
RP Gardner, RC (reprint author), Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
FU NIA NIH HHS [K24 AG031155, P01 AG019724, P50 AG023501, R01 AG026720, R01
AG05401]; NIDDK NIH HHS [R01 DK069406]; NIMH NIH HHS [R01 MH086498]
NR 30
TC 8
Z9 9
U1 2
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0364-5134
EI 1531-8249
J9 ANN NEUROL
JI Ann. Neurol.
PD MAR
PY 2014
VL 75
IS 3
BP 339
EP 341
DI 10.1002/ana.24121
PG 3
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AD8WS
UT WOS:000333547000004
PM 24550062
ER
PT J
AU Titulaer, MJ
Hoftberger, R
Iizuka, T
Leypoldt, F
McCracken, L
Cellucci, T
Benson, LA
Shu, H
Irioka, T
Hirano, M
Singh, G
Calvo, AC
Kaida, K
Morales, PS
Wirtz, PW
Yamamoto, T
Reindl, M
Rosenfeld, MR
Graus, F
Saiz, A
Dalmau, J
AF Titulaer, Maarten J.
Hoeftberger, Romana
Iizuka, Takahiro
Leypoldt, Frank
McCracken, Lindsey
Cellucci, Tania
Benson, Leslie A.
Shu, Huidy
Irioka, Takashi
Hirano, Makito
Singh, Gagandeep
Cobo Calvo, Alvaro
Kaida, Kenichi
Morales, Pamela S.
Wirtz, Paul W.
Yamamoto, Tomotaka
Reindl, Markus
Rosenfeld, Myrna R.
Graus, Francesc
Saiz, Albert
Dalmau, Josep
TI Overlapping demyelinating syndromes and anti-N-methyl-D-aspartate
receptor encephalitis
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID MYELIN-OLIGODENDROCYTE GLYCOPROTEIN; ACUTE DISSEMINATED
ENCEPHALOMYELITIS; NEUROMYELITIS-OPTICA; NMDAR ENCEPHALITIS; ANTIBODIES;
COMPLEMENT; SPECTRUM; DISORDERS; DIAGNOSIS; MOG
AB Objective
To report the clinical, radiological, and immunological association of demyelinating disorders with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis.
Methods
Clinical and radiological analysis was done of a cohort of 691 patients with anti-NMDAR encephalitis. Determination of antibodies to NMDAR, aquaporin-4 (AQP4), and myelin oligodendrocyte glycoprotein (MOG) was performed using brain immunohistochemistry and cell-based assays.
Results
Twenty-three of 691 patients with anti-NMDAR encephalitis had prominent magnetic resonance imaging (MRI) and/or clinical features of demyelination. Group 1 included 12 patients in whom anti-NMDAR encephalitis was preceded or followed by independent episodes of neuromyelitis optica (NMO) spectrum disorder (5 cases, 4 anti-AQP4 positive) or brainstem or multifocal demyelinating syndromes (7 cases, all anti-MOG positive). Group 2 included 11 patients in whom anti-NMDAR encephalitis occurred simultaneously with MRI and symptoms compatible with demyelination (5 AQ4 positive, 2 MOG positive). Group 3 (136 controls) included 50 randomly selected patients with typical anti-NMDAR encephalitis, 56 with NMO, and 30 with multiple sclerosis; NMDAR antibodies were detected only in the 50 anti-NMDAR patients, MOG antibodies in 3 of 50 anti-NMDAR and 1 of 56 NMO patients, and AQP4 antibodies in 48 of 56 NMO and 1 of 50 anti-NMDAR patients (p < 0.0001 for all comparisons with Groups 1 and 2). Most patients improved with immunotherapy, but compared with anti-NMDAR encephalitis the demyelinating episodes required more intensive therapy and resulted in more residual deficits. Only 1 of 23 NMDAR patients with signs of demyelination had ovarian teratoma compared with 18 of 50 anti-NMDAR controls (p = 0.011).
Interpretation
Patients with anti-NMDAR encephalitis may develop concurrent or separate episodes of demyelinating disorders, and conversely patients with NMO or demyelinating disorders with atypical symptoms (eg, dyskinesias, psychosis) may have anti-NMDAR encephalitis. Ann Neurol 2014;75:411-428
C1 [Titulaer, Maarten J.; Hoeftberger, Romana; Leypoldt, Frank; Rosenfeld, Myrna R.; Graus, Francesc; Saiz, Albert; Dalmau, Josep] Univ Barcelona, Hosp Clin Barcelona, Dept Neurol, E-08036 Barcelona, Spain.
[Titulaer, Maarten J.; Hoeftberger, Romana; Leypoldt, Frank; Rosenfeld, Myrna R.; Graus, Francesc; Saiz, Albert; Dalmau, Josep] August Pi i Sunyer Inst Biomed Res IDIBAPS, Barcelona, Spain.
[Titulaer, Maarten J.] Erasmus MC, Dept Neurol, Rotterdam, Netherlands.
[Hoeftberger, Romana] Med Univ Vienna, Inst Neurol, Vienna, Austria.
[Iizuka, Takahiro] Kitasato Univ, Sch Med, Dept Neurol, Tokyo, Kanagawa, Japan.
[Leypoldt, Frank] Univ Med Ctr Hamburg Eppendorf, Dept Neurol, Hamburg, Germany.
[McCracken, Lindsey; Dalmau, Josep] Univ Penn, Perelman Sch Med, Hosp Univ Penn, Dept Neurol & Neurosci, Philadelphia, PA 19104 USA.
[Cellucci, Tania] McMaster Univ, Dept Pediat, McMaster Childrens Hosp, Hamilton, ON, Canada.
[Benson, Leslie A.] Massachusetts Gen Hosp, Dept Child Neurol, Partners Pediat Multiple Sclerosis Ctr, Boston, MA 02114 USA.
[Benson, Leslie A.] Boston Childrens Hosp, Pediat Multiple Sclerosis & Related Disorders Cli, Boston, MA USA.
[Shu, Huidy] Pali Momi Med Ctr, Dept Neurol, Aiea, HI USA.
[Irioka, Takashi] Yokosuka Kyosai Hosp, Dept Neurol, Yokosuka, Kanagawa, Japan.
[Hirano, Makito] Kinki Univ, Fac Med, Sakai Hosp, Dept Neurol, Sakai, Osaka, Japan.
[Singh, Gagandeep] Dayanand Med Coll, Dept Neurol, Ludhiana, Punjab, India.
[Singh, Gagandeep] UCL, Dept Clin & Expt Epilepsy, London, England.
[Cobo Calvo, Alvaro] Univ Hosp Bellvitge, Dept Neurol, Barcelona, Spain.
[Kaida, Kenichi] Natl Def Med Coll, Dept Neurol, Tokorozawa, Saitama 359, Japan.
[Morales, Pamela S.] Pontificia Univ Catolica Chile, Dept Pediat, Santiago, Chile.
[Wirtz, Paul W.] Haga Hosp, Dept Neurol, The Hague, Netherlands.
[Yamamoto, Tomotaka] Tokyo Univ Hosp, Med Safety Management Ctr, Tokyo 113, Japan.
[Reindl, Markus] Med Univ Innsbruck, Dept Clin Neurol, A-6020 Innsbruck, Austria.
[Dalmau, Josep] Catalan Inst Res & Adv Studies ICREA, Barcelona, Spain.
RP Dalmau, J (reprint author), Univ Barcelona, IDIBAPS Hosp Clin, Serv Neurol, 143 Floor 5,Lab 503,Dept 2, E-08036 Barcelona, Spain.
EM Josep.dalmau@uphs.upenn.edu
RI Saiz, Albert/K-8236-2014;
OI Saiz, Albert/0000-0002-5793-8791; Reindl, Markus/0000-0003-2817-1402;
Rosenfeld, Myrna/0000-0001-5095-2534; Dalmau, Josep/0000-0001-5856-2813
FU Dutch Cancer Society; ErasmusMC fellowship; Fonds zur Forderung der
wissenschaftlichen Forschung, Austria [J3230, W1206, I916];
Forschungsforderungsfonds Hamburg Eppendorf Exzellenzjahr; NIH National
Institute of Neurologic Disorders and Stroke [RO1NS077851]; McKnight
Neuroscience of Brain Disorders award; Fundacio la Marato TV3 [101530,
101610]; Fondo de Investigaciones Sanitarias de la Seguridad Social,
Spain [PI11/01780]; A National MS Society; Ministry of Education,
Culture, Sports, Science, and Technology of Japan [25461297]; Kinki
University
FX This study was supported by a Dutch Cancer Society fellowship (M.J.T.);
an ErasmusMC fellowship (M.J.T.); the Fonds zur Forderung der
wissenschaftlichen Forschung, Austria (Project J3230, R.H.; Projects
W1206 and I916 [ERA-Net ERare project Eden], M.R.); the
Forschungsforderungsfonds Hamburg Eppendorf Exzellenzjahr (F.L.); the
NIH National Institute of Neurologic Disorders and Stroke (RO1NS077851,
J.D.); a McKnight Neuroscience of Brain Disorders award (J.D.); Fundacio
la Marato TV3 (101530, J.D.; 101610, A.S.); Fondo de Investigaciones
Sanitarias de la Seguridad Social, Spain (PI11/01780, J.D.); A National
MS Society Clinical Care Fellowship (L.A.B); Grants-in-Aids for
Scientific Research from the Ministry of Education, Culture, Sports,
Science, and Technology of Japan (25461297, M.H.); and a University
Research Grant from Kinki University (M.H.). The funding sources had no
role in the design, collection, analysis, or interpretation of the
study, nor in the writing of the article or decision to submit.
NR 32
TC 70
Z9 76
U1 1
U2 20
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0364-5134
EI 1531-8249
J9 ANN NEUROL
JI Ann. Neurol.
PD MAR
PY 2014
VL 75
IS 3
BP 411
EP 428
DI 10.1002/ana.24117
PG 18
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AD8WS
UT WOS:000333547000011
PM 24700511
ER
PT J
AU Shih, YYI
Yash, TV
Rogers, B
Duong, TQ
AF Shih, Yen-Yu Ian
Yash, Tiwari V.
Rogers, Bill
Duong, Timothy Q.
TI fMRI of Deep Brain Stimulation at the Rat Ventral Posteromedial Thalamus
SO BRAIN STIMULATION
LA English
DT Article
DE Striatum; Deep brain stimulation; fMRI; Thalamus; Rat; Isoflurane
ID BLOOD-FLOW; RESPONSES; BOLD; ACTIVATION; MRI; PLASTICITY
AB Background: Functional magnetic resonance imaging (fMRI) of deep brain stimulation (DBS) has potentials to reveal neuroanatomical connectivity of a specific brain region in vivo.
Objective: This study aimed to demonstrate frequency and amplitude tunings of the thalamocortical tract using DBS fMRI at the rat ventral posteromedial thalamus.
Methods: Blood oxygenation level dependent (BOLD) fMRI data were acquired in a total of twelve rats at a high-field 11.7 T MRI scanner with modulation of nine stimulus frequencies (1-40 Hz) and seven stimulus amplitudes (0.2-3.6 mA).
Results: BOLD response in the barrel cortex peaked at 25 Hz. The response increased with stimulus amplitude and reached a plateau at 1 mA. Cortical spreading depolarization (CSD) was observed occasionally after DBS that carries >10% BOLD waves spanning the entire ipsilateral cortex.
Conclusion: fMRI is sensitive to the frequency effect of DBS and has potential to investigate the function of a particular neuroanatomical pathway. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Shih, Yen-Yu Ian; Yash, Tiwari V.; Rogers, Bill; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA.
[Shih, Yen-Yu Ian] Univ N Carolina, Dept Neurol, Chapel Hill, NC 27599 USA.
[Shih, Yen-Yu Ian] Univ N Carolina, Biomed Res Imaging Ctr, Chapel Hill, NC 27599 USA.
[Shih, Yen-Yu Ian] Univ N Carolina, Dept Biomed Engn, Chapel Hill, NC 27599 USA.
[Yash, Tiwari V.] Univ Texas San Antonio, Dept Biomed Engn, San Antonio, TX 78249 USA.
[Duong, Timothy Q.] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA.
RP Shih, YYI (reprint author), Univ N Carolina, Dept Neurol, Expt Neuroimaging Lab, 130 Mason Farm Rd,CB 7513, Chapel Hill, NC 27599 USA.
EM shihy@unc.edu; duongt@uthscsa.edu
OI Shih, Yen-Yu Ian/0000-0001-6529-911X
FU American Heart Association [10POST4290091]; Clinical Translational
Science Awards (CTSA) [UL1RR025767]; San Antonio Area Foundation;
NIH/NINDS [R01 NS45879]; VA MERIT
FX This work was supported in part by the American Heart Association
(10POST4290091), Clinical Translational Science Awards (CTSA, parent
grant UL1RR025767), and San Antonio Area Foundation to Dr. Yen-Yu Ian
Shih and the NIH/NINDS R01 NS45879 and VA MERIT to Dr. Timothy Q. Duong.
NR 19
TC 8
Z9 8
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1935-861X
EI 1876-4754
J9 BRAIN STIMUL
JI Brain Stimul.
PD MAR-APR
PY 2014
VL 7
IS 2
BP 190
EP 193
DI 10.1016/j.brs.2013.11.001
PG 4
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AD7KH
UT WOS:000333442200006
PM 24309153
ER
PT J
AU Suemoto, CK
Apolinario, D
Nakamura-Palacios, EM
Lopes, L
Leite, REP
Sales, MC
Nitrini, R
Brucki, SM
Morillo, LS
Magaldi, RM
Fregni, F
AF Suemoto, Claudia Kimie
Apolinario, Daniel
Nakamura-Palacios, Ester Miyuki
Lopes, Leonardo
Paraizo Leite, Renata Elaine
Sales, Manuela Castro
Nitrini, Ricardo
Brucki, Sonia Maria
Morillo, Lilian Shafirovitz
Magaldi, Regina Miksian
Fregni, Felipe
TI Effects of a Non-focal Plasticity Protocol on Apathy in Moderate
Alzheimer's Disease: A Randomized, Double-blind, Sham-controlled Trial
SO BRAIN STIMULATION
LA English
DT Article
DE Apathy; Dementia; Alzheimer's disease; Cognition; Depression;
Transcranial direct current stimulation
ID DIRECT-CURRENT STIMULATION; PARKINSONS-DISEASE; DEMENTIA;
METHYLPHENIDATE; DEPRESSION; MEMORY; DIAGNOSIS; EFFICACY; BRAIN; MODEL
AB Background: Apathy is the most common neuropsychiatric symptom in Alzheimer's disease (AD) and it is associated with changes in prefrontal neural circuits involved with generation of voluntary actions. To date no effective treatment for apathy has been demonstrated.
Objective: We aimed to investigate the effects and safety of repetitive transcranial direct current stimulation (tDCS) on apathy in moderate AD patients.
Methods: Forty patients were randomized to receive either active or sham-tDCS over the left dorsolateral prefrontal cortex (DLPFC). Patients received six sessions of intervention during 2 weeks and were evaluated at baseline, at week 1 and 2, and after 1 week without intervention. Clinical raters, patients, and caregivers were blinded. The primary outcome was apathy. Global cognition and neuropsychiatric symptoms were examined as secondary outcomes.
Results: The mean MMSE score at baseline was 15.2 +/- 2.9 and the mean Apathy Scale score was 27.7 +/- 6.7. Changes on apathy scores over time were not different between active and sham tDCS (P = 0.552 for repeated measures). Further analyses confirm that changes from baseline did not differ between groups after the sixth session (active tDCS -1.95 (95%CI -3.49, -0.41); sham-tDCS -2.05 (95% Cl -3.68, 0.42); P = 0.9891. Similarly, tDCS had no effect on secondary outcomes (P > 0.40). tDCS was well tolerated and not associated with significant adverse effects.
Conclusion: In this adequately powered study for minimal clinically significant difference, our findings show that using the parameters we chose for this study, repeated anodal tDCS over the left DLPFC had no effect on apathy in elderly patients with moderate AD. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Suemoto, Claudia Kimie; Apolinario, Daniel; Lopes, Leonardo; Sales, Manuela Castro; Morillo, Lilian Shafirovitz; Magaldi, Regina Miksian] Univ Sao Paulo, Sch Med, Dept Internal Med, Discipline Geriatr, Sao Paulo, Brazil.
[Nakamura-Palacios, Ester Miyuki] Univ Fed Espirito Santo, Dept Physiol Sci, Vitoria, Espirito Santo, Brazil.
[Paraizo Leite, Renata Elaine] Univ Sao Paulo, Sch Med, LIM 22, Dept Pathol, Sao Paulo, Brazil.
[Nitrini, Ricardo; Brucki, Sonia Maria] Univ Sao Paulo, Sch Med, Dept Neurol, Sao Paulo, Brazil.
[Fregni, Felipe] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA.
[Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
RP Suemoto, CK (reprint author), Univ Sao Paulo, Dept Internal Med, Discipline Geriatr, Ave Doutor Arnaldo 455,Room 1353, Sao Paulo, Brazil.
EM cksuemoto@usp.br
RI Apolinario, Daniel/D-2816-2014; Suemoto, Claudia/C-7218-2012
OI Apolinario, Daniel/0000-0002-0261-129X; Suemoto,
Claudia/0000-0002-5942-4778
FU Scala Institute
FX Scala Institute.
NR 30
TC 15
Z9 16
U1 4
U2 22
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1935-861X
EI 1876-4754
J9 BRAIN STIMUL
JI Brain Stimul.
PD MAR-APR
PY 2014
VL 7
IS 2
BP 308
EP 313
DI 10.1016/j.brs.2013.10.003
PG 6
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AD7KH
UT WOS:000333442200023
PM 24262299
ER
PT J
AU Gunda, V
Bucur, O
Varnau, J
Vanden Borre, P
Bernasconi, MJ
Khosravi-Far, R
Parangi, S
AF Gunda, V.
Bucur, O.
Varnau, J.
Vanden Borre, P.
Bernasconi, M. J.
Khosravi-Far, R.
Parangi, S.
TI Blocks to thyroid cancer cell apoptosis can be overcome by inhibition of
the MAPK and PI3K/AKT pathways
SO CELL DEATH & DISEASE
LA English
DT Article
DE apoptosis; thyroid cancer; BRAF(V600E) inhibitor; orthotropic; TRAIL
ID TRAIL-INDUCED APOPTOSIS; DOWN-REGULATION; LEUKEMIA-CELLS; BRAF(V600E)
MUTATION; DEPENDENT MANNER; CARCINOMA-CELLS; MELANOMA-CELLS; SOLID
TUMORS; PHASE-I; B-RAF
AB Current treatment for recurrent and aggressive/anaplastic thyroid cancers is ineffective. Novel targeted therapies aimed at the inhibition of the mutated oncoprotein BRAF(V600E) have shown promise in vivo and in vitro but do not result in cellular apoptosis. TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a tumor-selective manner by activating the extrinsic apoptotic pathway. Here, we show that a TRAIL-R2 agonist antibody, lexatumumab, induces apoptosis effectively in some thyroid cancer cell lines (HTh-7, TPC-1 and BCPAP), while more aggressive anaplastic cell lines (8505c and SW1736) show resistance. Treatment of the most resistant cell line, 8505c, using lexatumumab in combination with the BRAF(V600E) inhibitor, PLX4720, and the PI3K inhibitor, LY294002, (triple-drug combination) sensitizes the cells by triggering both the extrinsic and intrinsic apoptotic pathways in vitro as well as 8505c orthotopic thyroid tumors in vivo. A decrease in anti-apoptotic proteins, pAkt, Bcl-xL, Mcl-1 and c-FLIP, coupled with an increase in the activator proteins, Bax and Bim, results in an increase in the Bax to Bcl-xL ratio that appears to be critical for sensitization and subsequent apoptosis of these resistant cells. Our results suggest that targeting the death receptor pathway in thyroid cancer can be a promising strategy for inducing apoptosis in thyroid cancer cells, although combination with other kinase inhibitors may be needed in some of the more aggressive tumors initially resistant to apoptosis.
C1 [Gunda, V.; Vanden Borre, P.; Bernasconi, M. J.; Parangi, S.] Harvard Univ, Sch Med, Endocrine Unit, Surg Unit,Massachusetts Gen Hosp,Thyroid Canc Res, Boston, MA 02115 USA.
[Bucur, O.; Khosravi-Far, R.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Bucur, O.; Khosravi-Far, R.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Bucur, O.] Acad Romana, Inst Biochem, Dept Mol Cell Biol, Bucharest, Romania.
[Varnau, J.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
RP Parangi, S (reprint author), Harvard Univ, Sch Med, Endocrine Unit, Surg Unit,Massachusetts Gen Hosp,Thyroid Canc Res, Wang ACC 460,15 Parkman St, Boston, MA 02115 USA.
EM sparangi@partners.org
RI Bucur, Octavian/G-2823-2010
OI Bucur, Octavian/0000-0002-8501-588X
FU National Institutes of Health [NIH-NCI R01 1R01CA149738-01A1]
FX We thank Gideon Bollag, Paul Lin at Plexxikon/Roche for providing us
with PLX4720; and Matthew Nehs and Andrew Scott Liss for technical
assistance. This work was supported by The National Institutes of Health
grant to Dr. Sareh Parangi (NIH-NCI R01 1R01CA149738-01A1).
NR 50
TC 15
Z9 17
U1 0
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD MAR
PY 2014
VL 5
AR e1104
DI 10.1038/cddis.2014.78
PG 13
WC Cell Biology
SC Cell Biology
GA AE1TW
UT WOS:000333754100008
PM 24603332
ER
PT J
AU Munoz, JL
Rodriguez-Cruz, V
Greco, SJ
Ramkissoon, SH
Ligon, KL
Rameshwar, P
AF Munoz, J. L.
Rodriguez-Cruz, V.
Greco, S. J.
Ramkissoon, S. H.
Ligon, K. L.
Rameshwar, P.
TI Temozolomide resistance in glioblastoma cells occurs partly through
epidermal growth factor receptor-mediated induction of connexin 43
SO CELL DEATH & DISEASE
LA English
DT Article
DE connexin 43; glioblastoma; resistance; temozolomide EGF receptor; stem
cell; immune therapy
ID MESENCHYMAL STEM-CELLS; CENTRAL-NERVOUS-SYSTEM; HUMAN GLIOMA-CELLS;
GAP-JUNCTIONS; INTERCELLULAR COMMUNICATION; MOLECULAR-MECHANISMS;
SIGNALING PATHWAY; PROTEIN; HEMICHANNELS; EXPRESSION
AB Glioblastoma Multiforme (GBM) is an aggressive adult primary brain tumor with poor prognosis. GBM patients develop resistance to the frontline chemotherapy, temozolomide (TMZ). As the connexins (Cx) have been shown to have a complex role in GBM, we investigated the role of Cx43 in TMZ resistance. Cx43 was increased in the TMZ-resistant low passage and cell lines. This correlated with the data in The Cancer Genome Atlas. Cx43 knockdown, reporter gene assays, chromatin immunoprecipitation assay, real-time PCR and western blots verified a role for Cx43 in TMZ resistance. This occurred by TMZ-resistant GBM cells being able to activate epidermal growth factor receptor (EGFR). In turn, EGFR activated the JNK-ERK1/2-AP-1 axis to induce Cx43. The increased Cx43 was functional as indicated by gap junctional intercellular communication among the resistant GBM cells. Cell therapy could be a potential method to deliver drugs, such as anti-EGF to tumor cells. Similar strategies could be used to reverse the expression of Cx43 to sensitize GBM cells to TMZ. The studies showed the potential for targeting EGF in immune therapy. These agents can be used in conjunction with stem cell therapy to treat GBM.
C1 [Munoz, J. L.] Rutgers Grad Sch Biomed Sci, Newark, NJ USA.
[Munoz, J. L.; Rodriguez-Cruz, V.; Greco, S. J.; Rameshwar, P.] Rutgers Sch Biomed Hlth Sci, New Jersey Med Sch, Dept Med, Newark, NJ 07103 USA.
[Ramkissoon, S. H.; Ligon, K. L.] Boston Childrens Hosp, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA.
[Ramkissoon, S. H.; Ligon, K. L.] Harvard Univ, Sch Med, Boston, MA USA.
[Ramkissoon, S. H.; Ligon, K. L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Rameshwar, P (reprint author), Rutgers Sch Biomed Hlth Sci, New Jersey Med Sch, Dept Med, 185 South Orange Ave,MSB E-585, Newark, NJ 07103 USA.
EM rameshwa@njms.rutgers.edu
FU F M Kirby Foundation; Research Initiative for Science Enhancement
Program at the University of Puerto Rico in Cayey [R25 GM59429]
FX This work was supported by the F M Kirby Foundation and this work is in
partial fulfillment of JLM's PhD thesis. VR-C was supported by the
Research Initiative for Science Enhancement Program at the University of
Puerto Rico in Cayey (R25 GM59429). We would also like to thank
Sukhwinder Singh, PhD and the Flow Cytometry and Immunology Core
Laboratory at New Jersey Medical School.
NR 36
TC 23
Z9 23
U1 3
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD MAR
PY 2014
VL 5
AR e1145
DI 10.1038/cddis.2014.111
PG 10
WC Cell Biology
SC Cell Biology
GA AE1TW
UT WOS:000333754100049
PM 24675463
ER
EF