Watch the first trailer of Jason Reitman’s ‘Labor Day,’ a drama starring Kate Winslet and Josh Brolin as characters who find themselves in an intriguing and seemingly improbable love relationship. ‘Labor Day’ was written and directed by Jason Reitman (‘Thank You for Smoking,’ Up in the Air’). It is a screen adaptation of the critically acclaimed literary novel of the same title by Joyce Maynard, who is also the author of the memoir, ‘At Home in the World,’ which revealed her relationship with the late J.D. Salinger. As with the novel, the movie begins in the year 1987 on Labor Day weekend. Notably deglamorized, the Oscar-winning actress Kate Winslet portrays Adele Wheeler, a depressed and reclusive divorced single mother of a 13-year-old son, Henry, who is portrayed by Gattlin Griffith. Per chance while out on a rare shopping trip, Adele and Henry meet up with a stranger, Frank Chanbers, who is portrayed by Josh Brolin. With more than a bit of hesitation, she gives the man, who is ragged looking and bleeding from his forehead, a ride home. After she has taken him in to stay in the house, he reveals that he is both a convicted murderer and a [...]Source: http://feedproxy.google.com/~r/RightCelebrity/~3/MVvK2coZrAQ/
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Thursday, October 31, 2013
Obama admin presses for delay in Iran sanctions
WASHINGTON (AP) — Vice President Joe Biden and senior Obama administration officials convinced a number of senators on Thursday to hold off on another round of Iran sanctions as Western powers test Tehran's willingness to scale back its nuclear aims.
The full-court press didn't sway every senator who participated in the hours-long, closed-door briefing, but the chances that the Senate Banking Committee would draft new, punitive measures next week just as negotiations occurred in Geneva diminished significantly.
"As one member of the committee, my attitude is if something is going on that may lead to a positive result, let's see where that ends up," said Sen. Mike Johanns, R-Neb., as he emerged from the session. "We can always pass a sanctions bill."
Sen. Dean Heller, R-Nev., said the administration was "making a good case" for delaying another round of penalties although he said he had not made a decision.
Joining Biden in the discussions with Democratic leadership and committee members were Secretary of State John Kerry and Treasury Secretary Jack Lew, a lineup that underscored the administration's strong desire to get Congress to wait on a new package of penalties. Although the White House insists that tough sanctions have forced Iran to negotiate, it wants Congress to pause to give negotiators flexibility in talks with Iran.
"I like John Kerry, I got a lot of trust in John Kerry," said Sen. Jon Tester, D-Mont., who explained that it might make sense for the committee to wait, finalize any legislation "and let them (the administration and Western powers) do their negotiations."
Unnerving for the administration is the prospect that a Senate panel would be crafting new sanctions at the same time as Iran and six world powers meet in Geneva next week for another round of negotiations.
The chairman of the Banking committee, Sen. Tim Johnson, D-S.D., said he was undecided on whether the panel would craft the bill next week. Republican and Democratic congressional aides indicated that it was unlikely on the same days as the international talks.
Western powers have been trying to determine Iran's seriousness in complying with demands it prove its nuclear program is peaceful since reformist President Hassan Rouhani took office in August. Both sides described their last round of negotiations as positive, with Tehran ready to discuss some curbs on programs that can create both atomic energy and the fissile core of nuclear arms.
Several lawmakers emerging from the session argued that this is no time to let up on Tehran.
"I have to hear something far more substantive to dissuade me from being an advocate for pursuing a new round of sanctions," said Sen. Bob Menendez, D-N.J., chairman of the Foreign Relations Committee who has repeatedly sponsored tough sanctions legislation.
Republican Sen. Mark Kirk of Illinois, who has often partnered with Menendez, said his response to the administration's intense lobbying was to keep pushing for sanctions, dismissing the latest talks with Tehran as "a long rope a dope."
"I think we need to keep rolling with the pressure," Kirk said. "Without sanctions, you have war. Sanctions are the only way to prevent a war. I don't want to condemn our allies and Israel to a war."
The Banking Committee is weighing a bill that would blacklist Iran's mining and construction sectors. It largely mirrors a House measure that passed overwhelmingly by a 400-20 vote in July. That bill also called for all Iranian oil sales to end by 2015.
The Senate bill may narrow that time frame, block international investment in more economic sectors, try to close off Iran's foreign accounts and tighten President Barack Obama's ability to waive requirements for allies and key trading partners who continue to do business with Iran.
The powerful American Israel Public Affairs Committee, which has considerable sway in Congress, favors more sanctions to stop Iran.
White House spokesman Jay Carney said Obama is not seeking an open-ended delay to new sanctions and believes there may come a point where additional economic penalties against Iran are necessary. Kerry told senators that the president wants to keep the current sanctions regime in place while negotiating with Iran.
Even if the administration succeeds in convincing Democratic leaders and Johnson to delay a vote, Kirk said he would try to attach new sanctions to the annual defense policy bill that the Senate could consider as early as the week of Nov. 12.
"I would look for every opportunity as a senator," he said.
Associated PressSource: http://hosted2.ap.org/APDEFAULT/89ae8247abe8493fae24405546e9a1aa/Article_2013-10-31-US-United-States-Iran/id-8253cd0d18af4a769c72a9bf7445fc3cRelated Topics: world series game 4 pauly d Panda Express Blurred Lines Lyrics drake
Houston we have a problem: Microgravity accelerates biological aging
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PUBLIC RELEASE DATE: 31-Oct-2013
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ShareContact: Cody Mooneyhan
cmooneyhan@faseb.org
301-634-7104
Federation of American Societies for Experimental Biology
New research in The FASEB Journal suggests that gravitational unloading significantly impairs the function of endothelial cells, as evidenced by gene expression studies conducted in space
Bethesda, MDAs nations strive to put humans farther into space for longer periods of time, the real loser in this new space race could be the astronauts themselves. That's because experiments conducted on the International Space Station involving cells that line the inner surfaces of blood vessels (endothelial cells) show that microgravity accelerates cardiovascular disease and the biological aging of these cells. These findings are presented in a new research report published in November 2013 issue of The FASEB Journal.
"Understanding the cellular and molecular events of senescence might help in finding preventive measures that are useful to improve the quality of life of millions of people," said Silvia Bradamante, a researcher involved in the work from the CNR-ISTM, Institute of Molecular Science and Technologies in Milan, Italy. "Our study further supports the role of oxidative stress in accelerating aging and disease."
In this report, Bradamante and colleagues examined endothelial cells in real microgravity aboard the International Space Station and conducted deep gene expression and protein analysis on the cells. They compared space-flown endothelial cells to endothelial cells cultured under normal gravity, looking for differences in gene expression and/or in the profile of secreted proteins. Space-flown cells differentially expressed more than 1,000 genes and secreted high amounts of pro-inflammatory cytokines. Ultimately, this induced significant oxidative stress, causing inflammation among endothelial cells, which in turn, led to atherosclerosis and cell senescence (biological aging).
"As we plan to send people deeper into space than ever before, and for longer flights, we've got to make sure that they remain in best health possible," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "We've evolved to rely on gravity to regulate our biology, and without it, our tissues become confused. Worst of all: they age faster!"
###
Receive monthly highlights from The FASEB Journal by e-mail. Sign up at http://www.faseb.org/fjupdate.aspx. The FASEB Journal is published by the Federation of the American Societies for Experimental Biology (FASEB). It is among the most cited biology journals worldwide according to the Institute for Scientific Information and has been recognized by the Special Libraries Association as one of the top 100 most influential biomedical journals of the past century.
FASEB is composed of 27 societies with more than 110,000 members, making it the largest coalition of biomedical research associations in the United States. Our mission is to advance health and welfare by promoting progress and education in biological and biomedical sciences through service to our member societies and collaborative advocacy.
Details: Silvia Versari, Giulia Longinotti, Livia Barenghi, Jeanette Anne Marie Maier, and Silvia Bradamante. The challenging environment on board the International Space Station affects endothelial cell function by triggering oxidative stress through thioredoxin interacting protein overexpression: the ESA-SPHINX experiment. FASEB J November 2013 27:4466-4475; doi:10.1096/fj.13-229195 ; http://www.fasebj.org/content/27/11/4466.abstract
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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
PUBLIC RELEASE DATE: 31-Oct-2013
[
]
ShareContact: Cody Mooneyhan
cmooneyhan@faseb.org
301-634-7104
Federation of American Societies for Experimental Biology
New research in The FASEB Journal suggests that gravitational unloading significantly impairs the function of endothelial cells, as evidenced by gene expression studies conducted in space
Bethesda, MDAs nations strive to put humans farther into space for longer periods of time, the real loser in this new space race could be the astronauts themselves. That's because experiments conducted on the International Space Station involving cells that line the inner surfaces of blood vessels (endothelial cells) show that microgravity accelerates cardiovascular disease and the biological aging of these cells. These findings are presented in a new research report published in November 2013 issue of The FASEB Journal.
"Understanding the cellular and molecular events of senescence might help in finding preventive measures that are useful to improve the quality of life of millions of people," said Silvia Bradamante, a researcher involved in the work from the CNR-ISTM, Institute of Molecular Science and Technologies in Milan, Italy. "Our study further supports the role of oxidative stress in accelerating aging and disease."
In this report, Bradamante and colleagues examined endothelial cells in real microgravity aboard the International Space Station and conducted deep gene expression and protein analysis on the cells. They compared space-flown endothelial cells to endothelial cells cultured under normal gravity, looking for differences in gene expression and/or in the profile of secreted proteins. Space-flown cells differentially expressed more than 1,000 genes and secreted high amounts of pro-inflammatory cytokines. Ultimately, this induced significant oxidative stress, causing inflammation among endothelial cells, which in turn, led to atherosclerosis and cell senescence (biological aging).
"As we plan to send people deeper into space than ever before, and for longer flights, we've got to make sure that they remain in best health possible," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "We've evolved to rely on gravity to regulate our biology, and without it, our tissues become confused. Worst of all: they age faster!"
###
Receive monthly highlights from The FASEB Journal by e-mail. Sign up at http://www.faseb.org/fjupdate.aspx. The FASEB Journal is published by the Federation of the American Societies for Experimental Biology (FASEB). It is among the most cited biology journals worldwide according to the Institute for Scientific Information and has been recognized by the Special Libraries Association as one of the top 100 most influential biomedical journals of the past century.
FASEB is composed of 27 societies with more than 110,000 members, making it the largest coalition of biomedical research associations in the United States. Our mission is to advance health and welfare by promoting progress and education in biological and biomedical sciences through service to our member societies and collaborative advocacy.
Details: Silvia Versari, Giulia Longinotti, Livia Barenghi, Jeanette Anne Marie Maier, and Silvia Bradamante. The challenging environment on board the International Space Station affects endothelial cell function by triggering oxidative stress through thioredoxin interacting protein overexpression: the ESA-SPHINX experiment. FASEB J November 2013 27:4466-4475; doi:10.1096/fj.13-229195 ; http://www.fasebj.org/content/27/11/4466.abstract
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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Source: http://www.eurekalert.org/pub_releases/2013-10/foas-hwh103113.php
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Knowing who their physician is boosts patient satisfaction
PUBLIC RELEASE DATE: 31-Oct-2013
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ShareContact: Craig Boerner
craig.boerner@vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
Knowing who your doctor is and a couple of facts about that person may go a long way toward improving patient satisfaction, according to a Vanderbilt study in the Journal of Orthopaedic Trauma.
Faced with the knowledge that between 82 percent and 90 percent of medical patients are unable to correctly name their treating physician following inpatient admission, orthopaedic trauma surgeon Alex Jahangir, M.D., and his Vanderbilt colleagues studied the effects of giving a randomized group of patients a simple biosketch card about their doctor.
What they learned is that patient satisfaction scores for the group receiving the card were 22 percent higher than those who did not receive the card.
"I think, in general, people recover better when they are more comfortable with the care they are receiving," said Jahangir, associate professor of Orthopaedic Surgery and Rehabilitation. "So it matters to patients and physicians who want a quick recovery, and now because of provisions in the Affordable Care Act, it matters to the institution because there are millions of dollars that can be at risk if patient satisfaction is low."
A percentage of Medicare reimbursement dollars beginning with 1 percent in FY 2013 and growing to 2 percent by 2017 is linked to patient satisfaction scores from the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) questions answered by patients, Jahangir said. Patient satisfaction determines 30 percent of performance scores for incentive payments, while clinical measures make up the other 70 percent.
"Whether we like it or not the reality of the world is that we are seeing more of an emphasis on not just outcomes, but the satisfaction of the care we deliver," Jahangir said. "So, while we should always strive for excellent outcomes and excellent care, we also can't forget that there is a human side of medicine and we need to do what we can to make sure that our patients are comfortable with the care that we are giving them. I believe it is important for us as physicians to really lead this charge of improving our patient's experience."
The Vanderbilt pilot study enrolled 212 randomized patients. One hundred received biosketch cards discreetly placed by a third party; 112 did not get cards. The patients were essentially the same in all variables, including injury type, insurance status and education.
To accurately gauge patient satisfaction, patients in the Vanderbilt study were contacted within two weeks of discharge to answer those same HCAHPS questions relating to their care.
In the end, the group who received a biosketch card had patient satisfaction scores 22 percent higher than the group who did not receive a biosketch card.
Each of the six physicians in Vanderbilt's Division of Orthopaedic Trauma participated in the study and, since that time, the nurse practitioners are now giving out cards to all patients.
"This is an easy, cheap intervention," Jahangir said. "As health care reimbursement shifts to reward quality rather than quantity, it is important to identify ways to improve the patient experience. This intervention is literally something that doesn't even cost a nickel but improves a patient's experience, and hopefully their recovery metrics that matter not only to the institution, but to patients and their physicians."
###
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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
PUBLIC RELEASE DATE: 31-Oct-2013
[
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ShareContact: Craig Boerner
craig.boerner@vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
Knowing who your doctor is and a couple of facts about that person may go a long way toward improving patient satisfaction, according to a Vanderbilt study in the Journal of Orthopaedic Trauma.
Faced with the knowledge that between 82 percent and 90 percent of medical patients are unable to correctly name their treating physician following inpatient admission, orthopaedic trauma surgeon Alex Jahangir, M.D., and his Vanderbilt colleagues studied the effects of giving a randomized group of patients a simple biosketch card about their doctor.
What they learned is that patient satisfaction scores for the group receiving the card were 22 percent higher than those who did not receive the card.
"I think, in general, people recover better when they are more comfortable with the care they are receiving," said Jahangir, associate professor of Orthopaedic Surgery and Rehabilitation. "So it matters to patients and physicians who want a quick recovery, and now because of provisions in the Affordable Care Act, it matters to the institution because there are millions of dollars that can be at risk if patient satisfaction is low."
A percentage of Medicare reimbursement dollars beginning with 1 percent in FY 2013 and growing to 2 percent by 2017 is linked to patient satisfaction scores from the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) questions answered by patients, Jahangir said. Patient satisfaction determines 30 percent of performance scores for incentive payments, while clinical measures make up the other 70 percent.
"Whether we like it or not the reality of the world is that we are seeing more of an emphasis on not just outcomes, but the satisfaction of the care we deliver," Jahangir said. "So, while we should always strive for excellent outcomes and excellent care, we also can't forget that there is a human side of medicine and we need to do what we can to make sure that our patients are comfortable with the care that we are giving them. I believe it is important for us as physicians to really lead this charge of improving our patient's experience."
The Vanderbilt pilot study enrolled 212 randomized patients. One hundred received biosketch cards discreetly placed by a third party; 112 did not get cards. The patients were essentially the same in all variables, including injury type, insurance status and education.
To accurately gauge patient satisfaction, patients in the Vanderbilt study were contacted within two weeks of discharge to answer those same HCAHPS questions relating to their care.
In the end, the group who received a biosketch card had patient satisfaction scores 22 percent higher than the group who did not receive a biosketch card.
Each of the six physicians in Vanderbilt's Division of Orthopaedic Trauma participated in the study and, since that time, the nurse practitioners are now giving out cards to all patients.
"This is an easy, cheap intervention," Jahangir said. "As health care reimbursement shifts to reward quality rather than quantity, it is important to identify ways to improve the patient experience. This intervention is literally something that doesn't even cost a nickel but improves a patient's experience, and hopefully their recovery metrics that matter not only to the institution, but to patients and their physicians."
###
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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Source: http://www.eurekalert.org/pub_releases/2013-10/vumc-kwt103113.php
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WWE Main Event results: Fight or Fright
Kofi Kingston vs. Ryback: WWE Main Event, Oct. 30, 2013Santino Marella vs. Heath Slater: WWE Main Event, Oct. 30, 2013The Great Khali vs. Fandango: WWE Main Event, Oct. 30, 2013Los Matadores vs. Los Locales: WWE Main Event, Oct. 30, 2013Kofi Kingston uses his words carefully: WWE App Exclusive, Oct. 28, 2013WWE Hell in a Cell 2013 KickoffKofi Kingston vs. Damien Sandow: WWE Hell in a Cell 2013 Kickoff
TAMPA, Fla. – On the night before Halloween, the WWE Universe was in for an action-packed edition of WWE Main Event. Kofi Kingston did his best to survive against the monstrous Ryback, while Heath Slater tried to avoid the venomous bite of Santino Marella’s Cobra. Fandango came face-to-face with the Frankenstein-ish Great Khali and Los Matadores charged into action with the costumed El Torito by their side.
Ryback def. Kofi Kingston
Kofi Kingston didn’t have to worry about Freddy Krueger or Jason Voorhees chasing him down on the night before Halloween. He did, however, have a massive monster coming for him on WWE Main Event, in the form of Ryback.
WWE Main Event Photos | Watch Ryback and Kofi Kingston do battle
Furious after back-to-back losses to CM Punk, The Big Guy was looking to get back in the win column Wednesday night. Kingston tried to use his rapid-fire kicks and speed to stick and move against his larger foe, but the monstrous Ryback was able to ground The Dreadlocked Dynamo.
After a series of kicks that wounded his lip, Ryback retreated to the floor. However, that might have been the worst place to go, as Kofi dove over the rope, crashing into his muscular foe.
Though The Wildcat staggered the beast with his stick and move offense, he never truly got a chance to get going. Ryback constantly cut him off, using his immense power to bulldoze the former Intercontinental Champion. He smiled as he brutalized Kingston, making it seem like it was easy.
It wasn’t a cakewalk for Ryback, though. Kingston spun over one of Ryback’s Meathook clotheslines, flooring the monster with devastating DDT. Ryback finally caught the speedy Kingston with a clubbing blow and Shell Shocked his foe to claim victory.
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Source: http://www.wwe.com/shows/wwemainevent/2013-10-30/results
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Results of the FREEDOM sub study reported at TCT 2013
PUBLIC RELEASE DATE: 31-Oct-2013
[
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ShareContact: Judy Romero
jromero@crf.org
Cardiovascular Research Foundation
Study examines the impact of insulin treatment status in diabetic patients with multivessel coronary artery disease
SAN FRANCISCO, CA October 31, 2013 According to a recent study of diabetic patients who underwent revascularization for multi-vessel coronary artery disease (CAD), patients treated with insulin experienced more major adverse cardiovascular events after revascularization than those not treated with insulin.
The findings of a sub group analysis of the FREEDOM trial were presented today at the 25th annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium. Sponsored by the Cardiovascular Research Foundation (CRF), TCT is the world's premier educational meeting specializing in interventional cardiovascular medicine.
The global prevalence of adult diabetes mellitus currently exceeds 6.4 percent (285 million) and is projected to increase to 7.7 percent (439 million) by 2030. In the United States, 26 percent of diabetics are treated with insulin; these patients comprise both patients with Type I diabetes as well as more advanced Type II diabetes. Insulin-treated patients are at increased risk for cardiovascular events after PCI and also have a higher risk of wound infection and mortality after coronary artery bypass surgery (CABG).
Results of the overall FREEDOM trial, which were first reported last year in the New England Journal of Medicine, found that coronary artery bypass grafting (CABG) reduces mortality and myocardial infarction rates compared to percutaneous coronary intervention (PCI), though it increases the chance of stroke. This FREEDOM sub group analysis examined the association of clinical outcomes after revascularization by insulin-treated diabetes mellitus (ITDM) status and the respective effect of CABG vs. PCI using first generation drug-eluting stents (PCI/DES). The primary endpoint was a composite of major adverse cardiac events including death, stroke and myocardial infarction analyzed using the logrank test and Cox regression to assess the interaction of treatment received and ITDM status.
A total of 1,850 diabetic patients with multi-vessel disease were randomized 1:1 to either CABG (894 patients) or PCI/DES (956 patients). Baseline and procedure characteristics were largely similar among the groups. A total of 602 patients (32.5 percent) had ITDM (PCI n=325, 34 percent; CABG n=277, 31 percent).
The estimated percentage of patients with a major adverse coronary event after five years was higher in the ITDM group compared to the non ITDM group (29 percent vs. 19 percent, respectively). Regardless of insulin treatment status, the estimated percentage of patients with major adverse coronary events after five years was higher among those that underwent PCI/DES (32 percent in the ITDM group and 25 percent in the non-ITDM group) compared to CABG (24 percent in the ITDM group and 16 percent in the non-ITDM group), although stroke rates were higher among CABG patients. In the ITDM group, the stroke rate was 7.5 for those who underwent CABG compared to 3.7 in those who had PCI/DES. In the non ITDM group, the stroke rate was 4.3 vs. 1.7 respectively.
"In patients with diabetes and multi-vessel coronary artery disease there are more major adverse cardiovascular events in patients treated with insulin than in those not treated with insulin," said study investigator George Dangas, MD, PhD. Dr. Dangas is Professor of Medicine at the Mount Sinai School of Medicine and Director of Cardiovascular Innovation at the Zena and Michael A. Wiener Cardiovascular Institute of the Mount Sinai Medical Center.
"However, the differences in clinical outcomes between CABG and PCI/DES were maintained regardless of the presence or absence of insulin treatment," Dr. Dangas said.
###
The FREEDOM trial was funded by NHLBI, NIH. Dr. Dangas reported no disclosures.
About CRF and TCT
The Cardiovascular Research Foundation (CRF) is an independent, academically focused nonprofit organization dedicated to improving the survival and quality of life for people with cardiovascular disease through research and education. Since its inception in 1991, CRF has played a major role in realizing dramatic improvements in the lives of countless numbers of patients by establishing the safe use of new technologies and therapies in interventional cardiovascular medicine. CRF is the sponsor of the Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium. Celebrating its 25th anniversary this year, TCT is the world's premier educational meeting specializing in interventional cardiovascular medicine. For more information, visit http://www.crf.org and http://www.tctconference.com.
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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
PUBLIC RELEASE DATE: 31-Oct-2013
[
]
ShareContact: Judy Romero
jromero@crf.org
Cardiovascular Research Foundation
Study examines the impact of insulin treatment status in diabetic patients with multivessel coronary artery disease
SAN FRANCISCO, CA October 31, 2013 According to a recent study of diabetic patients who underwent revascularization for multi-vessel coronary artery disease (CAD), patients treated with insulin experienced more major adverse cardiovascular events after revascularization than those not treated with insulin.
The findings of a sub group analysis of the FREEDOM trial were presented today at the 25th annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium. Sponsored by the Cardiovascular Research Foundation (CRF), TCT is the world's premier educational meeting specializing in interventional cardiovascular medicine.
The global prevalence of adult diabetes mellitus currently exceeds 6.4 percent (285 million) and is projected to increase to 7.7 percent (439 million) by 2030. In the United States, 26 percent of diabetics are treated with insulin; these patients comprise both patients with Type I diabetes as well as more advanced Type II diabetes. Insulin-treated patients are at increased risk for cardiovascular events after PCI and also have a higher risk of wound infection and mortality after coronary artery bypass surgery (CABG).
Results of the overall FREEDOM trial, which were first reported last year in the New England Journal of Medicine, found that coronary artery bypass grafting (CABG) reduces mortality and myocardial infarction rates compared to percutaneous coronary intervention (PCI), though it increases the chance of stroke. This FREEDOM sub group analysis examined the association of clinical outcomes after revascularization by insulin-treated diabetes mellitus (ITDM) status and the respective effect of CABG vs. PCI using first generation drug-eluting stents (PCI/DES). The primary endpoint was a composite of major adverse cardiac events including death, stroke and myocardial infarction analyzed using the logrank test and Cox regression to assess the interaction of treatment received and ITDM status.
A total of 1,850 diabetic patients with multi-vessel disease were randomized 1:1 to either CABG (894 patients) or PCI/DES (956 patients). Baseline and procedure characteristics were largely similar among the groups. A total of 602 patients (32.5 percent) had ITDM (PCI n=325, 34 percent; CABG n=277, 31 percent).
The estimated percentage of patients with a major adverse coronary event after five years was higher in the ITDM group compared to the non ITDM group (29 percent vs. 19 percent, respectively). Regardless of insulin treatment status, the estimated percentage of patients with major adverse coronary events after five years was higher among those that underwent PCI/DES (32 percent in the ITDM group and 25 percent in the non-ITDM group) compared to CABG (24 percent in the ITDM group and 16 percent in the non-ITDM group), although stroke rates were higher among CABG patients. In the ITDM group, the stroke rate was 7.5 for those who underwent CABG compared to 3.7 in those who had PCI/DES. In the non ITDM group, the stroke rate was 4.3 vs. 1.7 respectively.
"In patients with diabetes and multi-vessel coronary artery disease there are more major adverse cardiovascular events in patients treated with insulin than in those not treated with insulin," said study investigator George Dangas, MD, PhD. Dr. Dangas is Professor of Medicine at the Mount Sinai School of Medicine and Director of Cardiovascular Innovation at the Zena and Michael A. Wiener Cardiovascular Institute of the Mount Sinai Medical Center.
"However, the differences in clinical outcomes between CABG and PCI/DES were maintained regardless of the presence or absence of insulin treatment," Dr. Dangas said.
###
The FREEDOM trial was funded by NHLBI, NIH. Dr. Dangas reported no disclosures.
About CRF and TCT
The Cardiovascular Research Foundation (CRF) is an independent, academically focused nonprofit organization dedicated to improving the survival and quality of life for people with cardiovascular disease through research and education. Since its inception in 1991, CRF has played a major role in realizing dramatic improvements in the lives of countless numbers of patients by establishing the safe use of new technologies and therapies in interventional cardiovascular medicine. CRF is the sponsor of the Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium. Celebrating its 25th anniversary this year, TCT is the world's premier educational meeting specializing in interventional cardiovascular medicine. For more information, visit http://www.crf.org and http://www.tctconference.com.
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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Source: http://www.eurekalert.org/pub_releases/2013-10/crf-rot_2103113.php
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MVP! MVP!: Dominant Ortiz wins World Series prize
BOSTON (AP) — David Ortiz headed to the plate, ready to hit for the final time in the World Series. St. Louis catcher Yadier Molina stood up, spoke softly to his pal and twice patted him on the side.
By that point, even the Cardinals were members of the Big Papi fan club.
Ortiz walked off as the MVP after Boston won 6-1 Wednesday night in Game 6, capping a week in which he spurred the Red Sox with a mix of power, patience and a most timely pep talk.
"I know I'm one of the forces for this ballgame and I like to take things personal," he said. "And that's been my whole career, a challenge."
"I wasn't trying to be the guy, but I know I got to get something done to keep the line moving," he said. "I don't even have to do anything today, I guess, the rest of the team took over."
Ortiz drew four walks and three of them were intentional, including the last one in the eighth inning after talking with Molina.
Overall, Ortiz piled up totals that not even slow-pitch softball players dream about: He reached base a whopping 19 times in 25 plate appearances.
"Hey, let me tell you," he said. "I was hitting well, but it wasn't like I was hitting pitches right down the middle of the plate. They were trying their best to get me out."
When the game ended, Ortiz hoisted reliever Koji Uehara over his shoulder. He then raised the gleaming gold trophy with one hand, the crowning achievement of his career.
Now a three-time champion, Ortiz is the last link to the Red Sox team that swept the Cardinals in 2004 and ended an 86-year title drought.
The sellout crowd broke into thunderous chants of "MVP! MVP!" each time Ortiz batted. Quite a turnaround for the 37-year-old slugger who badly slumped in the AL championship series.
Ortiz hit 11 for 16 (.688) with two home runs and six RBIs against the Cardinals, and just missed a grand slam when Carlos Beltran robbed him by reaching over the short bullpen wall.
Asked to describe Ortiz, manager John Farrell paused.
"Well, I'd probably rather let his bat do the talking, because it's pretty special," he said.
Ortiz also drew eight walks and legged out a few infield hits, helped by St. Louis second baseman Matt Carpenter playing way out in shallow right field. At one point, Ortiz tied a Series record by reaching base in nine straight trips.
"He's as hot as anyone you're going to see this time of year," Cardinals manager Mike Matheny said. "We tried to make tough pitches in tough situations, tried to pitch around him at times."
Ortiz's .760 on-base percentage and batting average were the second-highest in Series history, trailing only Billy Hatcher's marks of .800 and .750 in 1990 for Cincinnati.
"David has been unbelievable his whole career this time of the year. It's his time of the year. I've been on the wrong side of it a few times," winning pitcher John Lackey said.
As Ortiz came up in the first inning, Molina and plate umpire Jim Joyce talked about him.
"This guy's unbelievable," Molina said on Fox audio.
"He's fun to watch," Joyce said.
Yet for all the impact he made swinging the bat in getting 11 of Boston's 41 hits — or just standing there and watching the Cardinals pitch around him — Ortiz made an equally important contribution with his words.
With St. Louis leading the Series 2-1 and the Red Sox scuffling in Game 4, Ortiz called his bearded band together for an impromptu huddle in the dugout.
Ortiz said he merely told the guys to relax, stay loose and appreciate the moment. His teammates told a different story after Boston rallied to win.
"It was like 24 kindergartners looking up at their teacher. He got everyone's attention and we looked him right in the eyes," said Jonny Gomes, who answered with a winning home run. "That message was pretty powerful."
That's also what the Red Sox expect from their Dominican-born thumper, known for his neatly tailored suits and dazzling diamond jewelry.
Whatever the Red Sox need, and whenever they need it, he's ready. When the Series shifted to St. Louis and there was no designated hitter, he adeptly moved from the DH spot to first base.
He did the same thing way back in the 2004 Series, and again in 2007 when the Red Sox swept Colorado.
As the Red Sox celebrated on the field after the final out, Ortiz considered what it meant to win a third title. Easy, he answered.
"That means I'm getting old," he said.
Associated PressSource: http://hosted2.ap.org/APDEFAULT/347875155d53465d95cec892aeb06419/Article_2013-10-31-World%20Series-MVP/id-9095bb42371f4226b1ad88e59f9f31acSimilar Articles: Texas A&m Football Cristy Nicole Deweese jim parsons iOS 7 download drake
Prosecutor reviewing facts in Georgia gym mat death
MACON, Ga. (AP) — A federal prosecutor said Thursday that he is conducting a formal review of facts and evidence in the death of a teenager whose body was found inside a rolled-up wrestling mat in his high school gym.
U.S. Attorney Michael Moore said that if he uncovers sufficient evidence to warrant a criminal civil rights investigation into the death of Kendrick Johnson he will ask the FBI to conduct it.
"I will follow the facts wherever they lead. My objective is to discover the truth," Moore said.
Moore said he's reviewing a previous investigation by a sheriff's office and two autopsies done on Johnson, along with photos, videos and other evidence and information. He said he's met with investigators and the attorneys for Johnson's family.
"I am committed to doing everything in my power to answer the questions that exist in this case, or as many of them as we can," Moore said.
The 17-year-old's body was found Jan. 11 stuck in an upright mat in the school gym after his parents reported him missing the night before. Lowndes County sheriff's investigators concluded Johnson died in a freak accident, but his family insists that someone must have killed him.
David S. Weinstein, a formal federal prosecutor now in private practice in Miami, said it's relatively unusual for federal authorities to go in and review an investigation once a local jurisdiction has closed it.
"There must be something in the information that was provided to him that led him to believe he needed to take another look at it," he said of Moore. "There must have been something that didn't pass the smell test."
Federal jurisdiction is relatively limited and federal authorities will only be able to open a criminal civil rights investigation if they find evidence that a law enforcement officer or someone acting as a law enforcement officer was involved in wrongdoing in the case. If they find, for example, that another person was responsible for a cover-up in the case, they would have to refer that evidence to local authorities to pursue, Weinstein said.
A southern Georgia judge on Wednesday ordered authorities to release all surveillance video that investigators reviewed. Johnson's father said after that ruling that he hoped the footage would contain clues about how he died.
Sheriff Chris Prine had previously released surveillance footage that showed Johnson entering the school gym the afternoon before his body was found. No one appeared to follow him inside.
Johnson's parents wanted to see video from the gym from the hours before their son entered until his body was discovered the next day. The sheriff had declined to release the footage without a court order because it shows other minor students who could be identified.
Johnson's body was stuck upside down in the middle of a wrestling mat that had been rolled up and propped upright behind bleachers.
The sheriff has said he suspects Johnson became trapped trying to retrieve a shoe that fell into the center of the large, rolled mat. A Georgia Bureau of Investigation medical examiner concluded that he died from positional asphyxia, meaning his body got stuck in a position in which he couldn't breathe.
Johnson's family had his body exhumed over the summer so they could get a second opinion from a private pathologist. Dr. William R. Anderson issued a report in August saying he detected hemorrhaging on the right side of Johnson's neck. He concluded the teenager died from blunt force trauma near his carotid artery and that the fatal blow appeared to be non-accidental. A lawyer for Johnson's parents filed court papers last week requesting that a judge order Lowndes County Coroner Bill Watson to hold a coroner's inquest after Watson declined the family's request to do so.
An attorney for Johnson's parents said in September that the autopsy's findings had been sent to local authorities and to Moore, as well as to the Civil Rights Division of the Justice Department.
The Georgia Bureau of Investigation has said it stands by the findings of the initial autopsy. The Justice Department said at the time that it had reviewed the state investigation file and didn't see "sufficient indication of a civil rights violation to authorize a civil rights investigation." But the Justice Department did say it was working with Moore and that his office was monitoring and evaluating the situation.
___
Associated Press writer Ray Henry in Atlanta contributed to this report.
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Naomi Watts on becoming Diana
Actor Naveen Andrews, left, actress Naomi Watts, director Oliver Hirschbiegel and producer Robert Bernstein, right, attend the premiere of "Diana" hosted by The Cinema Society, Linda Wells and Allure Magazine at the SVA Theater on Wednesday, Oct. 30, 2013 in New York. (Photo by Evan Agostini/Invision/AP)
Actor Naveen Andrews, left, actress Naomi Watts, director Oliver Hirschbiegel and producer Robert Bernstein, right, attend the premiere of "Diana" hosted by The Cinema Society, Linda Wells and Allure Magazine at the SVA Theater on Wednesday, Oct. 30, 2013 in New York. (Photo by Evan Agostini/Invision/AP)
Actress Naomi Watts attends the premiere of "Diana" hosted by The Cinema Society, Linda Wells and Allure Magazine at the SVA Theater on Wednesday, Oct. 30, 2013 in New York. (Photo by Evan Agostini/Invision/AP)
NEW YORK (AP) — When Naomi Watts was a struggling actress, she never would have imagined that one day she would play Princess Diana, one of the most famous women in the world, even after her death.
In fact, the thought makes her laugh.
"Yeah, that would sound a bit silly wouldn't it," said the actress at the New York premiere of the biopic "Diana" on Wednesday night.
Watts plays the Princess of Wales during roughly the last two years of her life. The story is based on the 2001 book "Diana: Her Last Love," chronicling her relationships with heart surgeon Hasnat Khan and Dodi Fayed.
Cas Anvar, who plays Fayed, would often marvel on set about the way Watts embodied the essence of Princess Diana. In fact, he says she even stayed in character between takes.
"It was quite surreal sometimes, but it was thrilling to be around, working with someone like that," Anvar said. "She kept in character all the time, so I never actually got to experience the Naomi side of things," he recalled. "I was more or less always interacting with Lady Di."
Watts says she tried to stay in character not because she's "as disciplined as Daniel Day-Lewis," but because the accent was so difficult to master.
Despite all her effort, few have been impressed with the film, which opens Friday. Reviews have been mostly negative thus far.
Naveen Andrews, who plays Dr. Khan, believes a big part of that is because Diana really was, as her nickname implies, the people's princess.
"Obviously in England, I think people feel a sense of ownership over her," he said. "They did when she was alive. Now they do that she's passed. It's a testament to her power that she can generate so much emotion and feeling."
Watts agrees: "Everyone feels they know her and they thought they had an opinion about who she was and their version of the story must be true and the comparisons that will be made inevitably."
Anvar says he thinks the strong opinions over the film are a good thing.
"Personally I would rather be part of a project that inspires massive debate and controversy than a project that just fades away with a whimper, he said. "Any kind of uproar or upheaval usually is a good thing and indicative of a good story."
Associated PressSource: http://hosted2.ap.org/APDEFAULT/4e67281c3f754d0696fbfdee0f3f1469/Article_2013-10-31-People-Naomi%20Watts/id-89992d38f12944a796c314e3f31d3758Similar Articles: 12 Years a Slave Jake Locker Sloane Stephens dairy queen Juan Pablo
Prosecutor reviewing facts in Ga. gym mat death
MACON, Ga. (AP) — A federal prosecutor said Thursday that he is conducting a formal review of facts and evidence in the death of a teenager whose body was found inside a rolled-up wrestling mat in his high school gym.
U.S. Attorney Michael Moore said that if he uncovers sufficient evidence to warrant a criminal or civil rights investigation into the death of Kendrick Johnson he will ask the FBI to conduct it.
"I will follow the facts wherever they lead. My objective is to discover the truth," Moore said.
Moore said he's reviewing a previous investigation by the sheriff's office and two autopsies done on Johnson, along with photos, videos and other evidence and information. He said he's met with investigators and the attorneys for Johnson's family to investigate the case.
"I am committed to do everything in my power to answer the questions that exist in this case, or as many of them as we can," Moore said.
The 17-year-old's body was found Jan. 11 stuck in an upright mat in the school gym after his parents reported him missing the night before. Lowndes County sheriff's investigators concluded Johnson died in a freak accident, but his family insists that someone must have killed him.
A southern Georgia judge on Wednesday ordered authorities to release all surveillance video that investigators reviewed. Johnson's father said after that ruling that he hoped the footage would contain clues to how he died.
Sheriff Chris Prine had previously released surveillance footage that showed Johnson entering the school gym the afternoon before his body was found. No one appeared to follow him inside.
Johnson's parents wanted to see video from the gym from the hours before their son entered until his body was discovered the next day. The sheriff had declined to release the footage without a court order because it shows other minor students who could be identified.
Johnson's body was stuck upside down in the middle of a wrestling mat that had been rolled up and propped upright behind bleachers.
The sheriff has said he suspects Johnson became trapped trying to retrieve a shoe that fell into the center of the large, rolled mat. A Georgia Bureau of Investigation medical examiner concluded that he died from positional asphyxia, meaning his body got stuck in a position in which he couldn't breathe.
Johnson's family had his body exhumed over the summer so they could get a second opinion from a private pathologist. Dr. William R. Anderson issued a report in August saying he detected hemorrhaging on the right side of Johnson's neck. He concluded the teenager died from blunt force trauma near his carotid artery and that the fatal blow appeared to be non-accidental. A lawyer for Johnson's parents filed court papers last week requesting a judge to order Lowndes County Coroner Bill Watson to hold a coroner's inquest after Watson declined the family's request to do so.
An attorney for Johnson's parents said in September that the autopsy's findings had been sent to local authorities and to Moore, as well as to the Civil Rights Division of the Justice Department.
The Georgia Bureau of Investigation has said it stands by the findings of the initial autopsy. The Justice Department said at the time that it had reviewed the state investigation file and didn't see "sufficient indication of a civil rights violation to authorize a civil rights investigation." But the Justice Department did say it was working with Moore and that his office was monitoring and evaluating the situation.
___
Associated Press writer Ray Henry in Atlanta contributed to this report.
Associated PressSource: http://hosted2.ap.org/APDEFAULT/386c25518f464186bf7a2ac026580ce7/Article_2013-10-31-US-Wrestling-Mat-Death/id-5c5bd681314c4792bc2804edf614572fSimilar Articles: BBM Dario Franchitti emmys jim parsons Obama Syria
Microsoft needs your help to nail the Windows 8.1 update 0xc1900101 Blue Screens
October 31, 2013
If you've been having trouble upgrading from Windows 8 to Windows 8.1, and are encountering Blue Screens marked 0xc1900101 - 0x40017 or 0xC1900101-0x20017, 0xC1900101-0x40019 or 0xc1900101 - 0x30018, there may be a fix for your problems. But if none of the remedies offered here get you upgraded, please head to the Microsoft Answers forum and post details about your configuration. Because after two weeks of trying, Microsoft still hasn't figured out what's causing the problem, and your input may help.
On Oct. 18 I wrote about the show-stopper bug for many people upgrading from Windows 8 to Windows 8.1. Martin Dixon posted the original description on the Microsoft Answers forum, shortly after the Windows 8.1 upgrade rolled out:
I have downloaded the Windows 8.1 update from the store but cannot get it to install. Each time I try, I get to the point where it is "getting my devices ready", then the PC restarts to a blue screen with error message. It then tries to recover the installation, fails, then restores Windows 8. When the system boots up after this, I get a message saying:
"Couldn't update to Windows 8.1
Sorry, we couldn't complete the update to Windows 8.1. We've restored your previous version of Windows to this PC.
0xC1900101 - 0x40017"
There is no explanation as to why the update couldn't be completed. Any ideas how to resolve this?
To date, almost 400 posts on that thread -- plus hundreds more on several additional, similar threads -- have led to a small handful of customer-discovered solutions, but no definitive workaround that everyone can apply.
Here are the approaches that seem to work for some people:
- If you have SteelSeries peripherals, running the SteelSeries Engine driver, uninstall it before re-trying the upgrade.
- If you have an Asus N53 dual-band PCI-e wireless adapter, pull it. If necessary, find another way to download the upgrade.
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‘X-Men: Days of Future Past’ Trailer (Video)
The first ‘X-Men: Days of Future Past’ trailer has hit the Web! Brian Singer directs an all-star cast — Hugh Jackman, Jennifer Lawrence, Halle Berry, Patrick Stewart, Ian McKellen, Anna Paquin, James McAvoy, Michael Fassbender, and others, both returning cast and newcomers — in the highly anticipated superhero movie. This glimpse of the upcoming movie, the latest installment of the Marvel comic book franchise, has fueled excitement. It is a sequel-prequel to the previous X-Men movies — ‘X-Men: The Last Stand’ and ‘X-Men: First Class’ — and as such, it brings back the beloved mutant characters from both movies. The trailer offers much that its intriguing as it finds Hugh Jackman (picture above) as The Wolverine, along with the mutants as they confront challenges in two different time periods. It serves to bring together a staggering number of characters all in one movie. It all comes about when Professor X (Patrick Stewart) and Magneto (Ian McKellen) send Wolverine back into the past so that he warn their younger selves — portrayed, respectively by James McAvoy and Michael Fassbender — of what can happen. The mastermind of this disaster to come is the villain Bolivar Trask, portrayed by Peter Dinklage (‘Game [...]Source: http://feedproxy.google.com/~r/RightCelebrity/~3/x2adx_15Wkw/
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Old drug may teach new tricks in treating infectious diseases, cancer
PUBLIC RELEASE DATE: 30-Oct-2013
[
]
ShareContact: Kathleen Phillips
ka-phillips@tamu.edu
979-845-2872
Texas A&M AgriLife Communications
COLLEGE STATION Meclizine, an over-the-counter drug used for decades to treat nausea and motion sickness, has the potential for new uses to treat certain infectious diseases and some forms of cancer, according to Dr. Vishal M. Gohil, Texas A&M AgriLife Research biochemist.
"Clearly this drug has many potential new applications," Gohil said. "And now that we know its new target within the cell, we can start to explore ways of using it to treat other diseases. We can 'repurpose' this drug."
The research on meclizine appears in the current online version of the Journal of Biological Chemistry.
"We found a particular enzyme which is inhibited by meclizine has been proposed (in other research) to be a drug target for the treatment of many diseases, including infectious diseases like malaria and African sleeping sickness," Gohil said. "And this pathway has also been proposed to be a critical pathway for the proliferation of cancer cells."
Gohil said his research, which included collaboration with scientists at Harvard Medical School and Massachusetts General Hospital, the University of Rochester and the University of Guelph, had already shown that the drug also works in the treatment of heart attack and stroke.
Meclizine is an antihistamine, synthesized in the 1950s and later found to be useful for treating nausea, motion sickness and vertigo.
Gohil, who also is an assistant professor of biochemistry and biophysics at Texas A&M University, said he started working on the compound when he identified it in a drug-screening experiment aimed at discovering compounds or drugs that inhibit mitochondrial respiration, a process that provides energy to cells.
Mitochondria are structures found in the cells of all eukaryotes, organisms with one or more cells containing a nuclei and organelles that perform specific tasks. Enclosed in membrane, mitochondria are responsible for supplying the cell with energy and are connected to a cell's life and death.
"When that drug screen identified meclizine, it was a bit of a surprise for us, because this compound had been in the market for several years and had never been linked to mitochondrial respiration," Gohil said. "It's a known drug, and was known to target a few of the molecules within the cell."
But unlike other classes of antihistamine, he noted, meclizine has a unique property which allows it to be used for the treatment of nausea and motion sickness, while most other antihistamines cannot.
"So there was this unique thing about this particular antihistamine," Gohil noted. "And it is well-tolerated so the toxicological profile is very acceptable, so it doesn't have to be sold under strict regulations."
"With that kind of profile, when we saw it in our drug screen we got excited about it because we could see that it decreases cellular oxygen consumption or respiration," he said. "We started trying to figure out the mechanism and to see if it could have any clinical benefit and application."
Gohil said for certain diseases like stroke, heart attack and some neurological diseases, previous medical research has shown that if mitochondrial respiration can be turned down, it could be beneficial for treatment.
"The way many of the cells die during the heart attack or stroke is connected to mitochondrial respiration, so the idea was that if you can turn down the respiration, then it will prevent death," he said. "This is exactly what we found when used meclizine in models of heart attack, stroke and even Huntington disease. We have a drug with a known clinical use and have identified a new biochemical target within the cells, so that opens up new applications."
He said when he and colleagues started studying the mechanism of this drug in terms of how it is inhibiting mitochondrial respiration, they made a couple of fundamental observations. "First, when we add this drug to the whole cells, we see reduced respiration, not rapidly but slowly," he said.
The researchers then added the drug to isolated mitochondria, which is the main site of respiration within the cells.
"But we did not see an effect, so that gave us the idea that this drug may not be directly targeting one of the enzymes of mitochondria which are required for or participates in consuming oxygen," Gohil said. "We used that clue to figure out how non-mitochondrial pathways could be targeted by this drug."
He used an unbiased metabolic profiling approach, a new technology that gives a snapshot of metabolite levels before and after the treatment of a drug so researchers can get an idea of how this drug is perturbing these metabolites.
"Through metabolic profiling, we found one particular metabolite - phosphoethanolamine - was in fact 'going through the roof' within a few hours of the treatment," Gohil said. "We got excited about that."
He explained that phosphoethanolamine is an intermediate in a biosynthetic pathway of a common phospholipid that forms the membrane around the cells. It is present in all living matter from the lower organisms such as bacteria all the way to humans. Thus, finding that the metabolite that was elevated when cells were treated with meclizine indicated a link between this pathway, or metabolite, and respiration.
"Our research showed that if we just take this metabolite and directly add it to mitochondria, it actually inhibits the respiration," Gohil said. "The reason we could use the drug for infectious disease or cancer is not because it inhibits respiration but because it inhibits a phospholipid biosynthetic enzyme that is required to form the building blocks of membranes."
###
[
Share]
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
PUBLIC RELEASE DATE: 30-Oct-2013
[
]
ShareContact: Kathleen Phillips
ka-phillips@tamu.edu
979-845-2872
Texas A&M AgriLife Communications
COLLEGE STATION Meclizine, an over-the-counter drug used for decades to treat nausea and motion sickness, has the potential for new uses to treat certain infectious diseases and some forms of cancer, according to Dr. Vishal M. Gohil, Texas A&M AgriLife Research biochemist.
"Clearly this drug has many potential new applications," Gohil said. "And now that we know its new target within the cell, we can start to explore ways of using it to treat other diseases. We can 'repurpose' this drug."
The research on meclizine appears in the current online version of the Journal of Biological Chemistry.
"We found a particular enzyme which is inhibited by meclizine has been proposed (in other research) to be a drug target for the treatment of many diseases, including infectious diseases like malaria and African sleeping sickness," Gohil said. "And this pathway has also been proposed to be a critical pathway for the proliferation of cancer cells."
Gohil said his research, which included collaboration with scientists at Harvard Medical School and Massachusetts General Hospital, the University of Rochester and the University of Guelph, had already shown that the drug also works in the treatment of heart attack and stroke.
Meclizine is an antihistamine, synthesized in the 1950s and later found to be useful for treating nausea, motion sickness and vertigo.
Gohil, who also is an assistant professor of biochemistry and biophysics at Texas A&M University, said he started working on the compound when he identified it in a drug-screening experiment aimed at discovering compounds or drugs that inhibit mitochondrial respiration, a process that provides energy to cells.
Mitochondria are structures found in the cells of all eukaryotes, organisms with one or more cells containing a nuclei and organelles that perform specific tasks. Enclosed in membrane, mitochondria are responsible for supplying the cell with energy and are connected to a cell's life and death.
"When that drug screen identified meclizine, it was a bit of a surprise for us, because this compound had been in the market for several years and had never been linked to mitochondrial respiration," Gohil said. "It's a known drug, and was known to target a few of the molecules within the cell."
But unlike other classes of antihistamine, he noted, meclizine has a unique property which allows it to be used for the treatment of nausea and motion sickness, while most other antihistamines cannot.
"So there was this unique thing about this particular antihistamine," Gohil noted. "And it is well-tolerated so the toxicological profile is very acceptable, so it doesn't have to be sold under strict regulations."
"With that kind of profile, when we saw it in our drug screen we got excited about it because we could see that it decreases cellular oxygen consumption or respiration," he said. "We started trying to figure out the mechanism and to see if it could have any clinical benefit and application."
Gohil said for certain diseases like stroke, heart attack and some neurological diseases, previous medical research has shown that if mitochondrial respiration can be turned down, it could be beneficial for treatment.
"The way many of the cells die during the heart attack or stroke is connected to mitochondrial respiration, so the idea was that if you can turn down the respiration, then it will prevent death," he said. "This is exactly what we found when used meclizine in models of heart attack, stroke and even Huntington disease. We have a drug with a known clinical use and have identified a new biochemical target within the cells, so that opens up new applications."
He said when he and colleagues started studying the mechanism of this drug in terms of how it is inhibiting mitochondrial respiration, they made a couple of fundamental observations. "First, when we add this drug to the whole cells, we see reduced respiration, not rapidly but slowly," he said.
The researchers then added the drug to isolated mitochondria, which is the main site of respiration within the cells.
"But we did not see an effect, so that gave us the idea that this drug may not be directly targeting one of the enzymes of mitochondria which are required for or participates in consuming oxygen," Gohil said. "We used that clue to figure out how non-mitochondrial pathways could be targeted by this drug."
He used an unbiased metabolic profiling approach, a new technology that gives a snapshot of metabolite levels before and after the treatment of a drug so researchers can get an idea of how this drug is perturbing these metabolites.
"Through metabolic profiling, we found one particular metabolite - phosphoethanolamine - was in fact 'going through the roof' within a few hours of the treatment," Gohil said. "We got excited about that."
He explained that phosphoethanolamine is an intermediate in a biosynthetic pathway of a common phospholipid that forms the membrane around the cells. It is present in all living matter from the lower organisms such as bacteria all the way to humans. Thus, finding that the metabolite that was elevated when cells were treated with meclizine indicated a link between this pathway, or metabolite, and respiration.
"Our research showed that if we just take this metabolite and directly add it to mitochondria, it actually inhibits the respiration," Gohil said. "The reason we could use the drug for infectious disease or cancer is not because it inhibits respiration but because it inhibits a phospholipid biosynthetic enzyme that is required to form the building blocks of membranes."
###
[
Share]
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Source: http://www.eurekalert.org/pub_releases/2013-10/taac-odm103013.php
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